Tag Archives: aging

How old is your dog? Open-science project is studying how dogs age, and you can join it

We’ve all heard the saying that one dog year is roughly equivalent to seven human years. But new research is working to find out more about how dogs progress through life — and, in turn, teach us about how we, ourselves, age.

Image via Pixabay.

It is true that dogs age faster than humans. However, according to researchers behind the Dog Aging Project (DAP), founded in 2018, the details are a bit murky. Saying that one human year is equivalent to seven dog years is a very broad simplification; big dogs tend to age the fastest, around 10 times as fast as humans, while little breeds age slower, about five times as fast as humans.

In other words, there is still much we don’t know about how man’s best friend grows old. Which is why the DAP was set up.

A dog’s life

“This is a very large, ambitious, wildly interdisciplinary project that has the potential to be a powerful resource for the broader scientific community,” said Joshua Akey, a professor in Princeton’s Lewis-Sigler Institute for Integrative Genomics and a member of the Dog Aging Project’s research team.

“Personally, I find this project exciting because I think it will improve dog, and ultimately, human health.”

The project is the largest undertaking to date that looks into canine aging and longevity. It currently involves tens of thousands of dogs of all breeds, sizes, and backgrounds, data from which goes into an open-source repository for veterinarians and scientists to use in the future. This wealth of data can be used to assess how well a particular dog is faring for their age, the researchers behind the DAP explain and help further our understanding of healthy aging in both dogs and humans.

It is set to run for at least 10 years in order to gather the data required. So far, over 32,000 dogs and their owners have joined the program, and recruitment is still ongoing. The owners of these dogs agreed to fill out annual surveys and take various measurements of their dogs to be used in the program. Some of them have also been asked to collect DNA material via cheek swabs for the researchers to sample. In addition, veterinarians associated with the program across the USA submit fur, blood, and other required samples from the dogs enrolled in the program (collectively known as the “DAP Pack”).

“We are sequencing the genomes of 10,000 dogs,” Akey said. “This will be one of the largest genetics data sets ever produced for dogs, and it will be a powerful resource not only to understand the role of genetics in aging, but also to answer more fundamental questions about the evolutionary history and domestication of dogs.”

The end goal of the program is to isolate specific biomarkers of aging in dogs. These should translate well to humans, the team explains. Dogs experience almost the same diseases and functional declines related to age as humans, veterinary care of dogs mirrors human healthcare in many ways, and dogs very often share living environments with humans. That last factor is very important as the environment is a main driver of aging and cannot be replicated in the lab.

Given that dogs share our environment, age similarly to us, but are much shorter-lived than humans, we have an exciting opportunity to identify factors that promote a healthy lifespan, and to find the signs of premature aging.

The oldest 300 dogs in the program will have their DNA sequenced as part of the ‘super-centenarian study. The team hopes to start this process in a few months. By that time, they will also open their entire anonymized dataset for researchers around the world to study.

If you live in the USA and would like to help, you and your doggo can enroll here.

The paper “An Open Science study of ageing in companion dogs” has been published in the journal Nature.

Study on mice: Exercising later in life can keep your muscles young

Exercising can not only make you feel younger, but it can also actually keep you younger as well. A study on mice suggests that exercising, even later in life, can do wonders for your muscles. In addition to underscoring the importance of staying active, the study could also help us uncover some of the secrets of rejuvenation.

Even though some diseases are inherited, we can still improve our overall health through lifestyle choices such as diet and exercise. Still, whatever the reason, the genes related to some of these conditions must be expressed for them to develop. So how does this happen?

A new study has brought us closer to an answer by mapping the genetic changes involved in rejuvenating the muscle cells of elderly mice put on an exercise program.

Turning genes on and off

The analysis centers on DNA, the “blueprint” for our bodies. DNA consists of four bases, called cytosine, guanine, adenine, and thymine, and the process used to help manage these massive helixes: a methyl molecule composed of one carbon and three hydrogen atoms. These atoms attach themselves to one of the four bases (cytosine) to form what’s known as a CpG site.

When this occurs, the CpG becomes methylated and the site produces proteins to regulate something in the body — whatever that something may be. In contrast, the region becomes unmethylated when you lose that methyl group, turning that gene off. In this way, a process called DNA methylation can promote or inhibit the expression of specific genes — whether it’s stopping a tumor, preventing cancer, or activating genes responsible for causing wrinkles in old age. This process is constant, occurring billions of times a second in every cell throughout the body, and we’re just starting to understand it.

DNA methylation is one of the many mechanisms of epigenetics, where inborn or acquired changes in DNA don’t touch the actual sequence – meaning a person can potentially reverse things like fat deposits through diet or exercise. More and more studies are starting to suggest that this is an unharnessed and robust process, linked to longevity and the regulation of lifespan in most organisms on earth.

The current study attempts to further this theory using lifestyle interventions such as exercise to roll back genetic aging in skeletal muscle – measuring the animal’s ‘epigenetic clock’ for accuracy. This clock is measured via methylation levels in the blood to reflect exposures and disease risks independent of chronological age, providing an early-warning system and a true representation of a period of existence.

Kevin Murach, an assistant professor at the University of Arkansas, says, “DNA methylation changes in a lifespan tend to happen in a somewhat systematic fashion. To the point, you can look at someone’s DNA from a given tissue sample and with a fair degree of accuracy predict their chronological age.”

Using exercise to turn back the clock

The study design was relatively simple: mice nearing the end of their natural lifespan, at 22 months, were given access to a weighted exercise wheel to ensure they built muscle. They required no coercion to run on the wheel, with older mice running from six to eight kilometers a day, mostly in spurts, and younger mice running up to 10-12 kilometers.

Results from the elderly mice after two months of weighted wheel running suggested they were the epigenetic age of mice eight weeks younger, compared to sedentary mice of the same maturity.

The team also used the epigenetic clock to map a multitude of genes involved in the formation and function of muscles, including those affected by exercise. Blood work indicated that the genes usually over methylated (hypermethylated) in old age resumed normal methylation in the active aged mice, unlike those mapped in their sedentary counterparts.

For instance, the rbm10 gene is usually hypermethylated in old age, disrupting the production of proteins involved in motor neuron survival, muscle weight & function, and the growth of striated muscle. Here it was shown to undergo less methylation in older mice who exercised, improving its performance. Normal methylation levels also resumed across the Timm8a1 gene, keeping mitochondrial function and oxidant defense at workable levels – even where neighboring sites exhibited dysfunctional epigenetic alterations.

More work is needed to harness DNA methylation

Murach notes that when a lifespan is measured incrementally in months, as with this mouse strain, an extra eight weeks — roughly 10 percent of that lifespan — is a noteworthy gain, further commending the importance of exercise in later life.

He adds: that although the connection between methylation and aging is clear, methylation and muscle function are less clear. Despite these sturdy results, Murach will not categorically state that the reversal of methylation with exercise is causative for improved muscle health. “That’s not what the study was set up to do,” he explained. However, he intends to pursue future studies to determine if “changes in methylation result in altered muscle function.”

And, “If so, what are the consequences of this?” he continued. “Do changes on these very specific methylation sites have an actual phenotype that emerges from that? Is it what’s causing aging or is it just associated with it? Is it just something that happens in concert with a variety of other things that are happening during the aging process? So that’s what we don’t know.”

He summarizes that once the medical community has mapped the mechanics of dynamic DNA methylation in muscle, their work could provide modifiable epigenetic markers to improve muscle health in the elderly. 

Pollution could be sucking the youth out of you, quite literally

Exposure to pollution in all its forms could be making us age faster, according to new research.

Image credits Mark Roentahlenberg.

Our everyday exposure to UV rays, ozone, cigarette smoke, industrial chemicals, and other pollutants might be even more damaging than we’ve believed. Such factors can lead to the production of free radicals in our bodies, highly reactive chemical molecules that damage tissues or DNA. A new study from West Virginia University, in collaboration with the University of Minnesota, reports that unrepaired DNA damage incurred from these radicals can cause us to age faster.

From their research on aging and cell damage in animals, the team is confident in the effect pollution could have on these factors in humans.

Harsh use

“By the time [a genetically-modified mouse used in the study] is 5 months old, it’s like a 2-year-old mouse,” said Eric Kelley, associate professor and associate chair of research in the School of Medicine’s Department of Physiology and Pharmacology.

“It has all the symptoms and physical characteristics. It has hearing loss, osteoporosis, renal dysfunction, visual impairment, hypertension, as well as other age-related issues. It’s prematurely aged just because it has lost its ability to repair its DNA.”

Kelley and his team used genetically modified mice for their study. These animals had the data encoding a certain protein removed from their hematopoietic stem cells, undifferentiated immune cells that later mature into white blood cells. This protein is a key DNA-repairing component in the mammalian body, and without it, the team could observe what effects their ever-decaying DNA strands would cause to the mice’s cells.

In rough terms, the team explains, a 2-year-old mouse is about as old as a human in their late 70s to early 80s.

These genetically engineered mice showed more markers of senescence (aging), cell damage, and oxidation in their immune cells compared to control mice. However, The damage extended beyond the immune system, with the experimental mice showing aged and damaged cells in organs including the liver and kidneys. This, they note, suggests that unrepaired DNA damage can lead to premature aging throughout an individual’s body.

The oxidation damage observed is largely due to the action of free radicals. There are two main ways that free radicals make their way into our bodies. The first is unavoidable — oxidative phosphorylation. It’s basically what happens after digestion, the step in which food is actually oxidized in our cells to produce energy. Without it, we couldn’t be alive. However, pollution can also introduce these bad chemicals.

Chemical pollutants such as smoke from exhaust or cigarettes can lead to the formation of free radicals inside the body through the interactions they have with chemicals and tissues. Additionally, radiation treatments like those used against cancer can transfer energy to the water molecules in our body, which can break apart into free radicals.

Our bodies do have tools on hand to limit the effects of these free radicals, but nowhere near enough to resist the pollution levels we’re seeing today.

“A cigarette has over 10 to the 16th free radicals per puff, just from combusted carbon materials,” Kelley said. “We have mechanisms in the mitochondria that mop free radicals up for us, but if they become overwhelmed — if we have over-nutrition, if we eat too much junk, if we smoke — the defense mechanism absolutely cannot keep up”.

Furthermore, as we age, these defenses become less and less effective, as our bodies wear out. Eventually, invariably, the oxidants gain the upper hand, the damage they cause starts outweighing our bodies’ repair capacity. Many of the characteristics associated with aging are caused by this. But, the team proposes, if we’re exposed to more pollutants, and accumulate a greater level of free radicals in the body, that aging will take place sooner.

“I come from an Appalachian background,” Kelley said. “And, you know, I’d go to funerals that were in some old house — an in-the-living-room-with-a-casket kind of deal — and I’d look at people in there, and they’d be 39 or 42 and look like they were 80 because of their occupation and their nutrition.”

“The impact is less on lifespan and more on healthspan,” he adds. “If you could get people better access to healthcare, better education, easier ways for them to participate in healthier eating and a healthier lifestyle, then you could improve the overall economic burden on the population of West Virginia and have a much better outcome all the way around.”

Although we have a few pharmaceutical options to deal with free radicals, the team says it’s best to prevent their accumulation in the first place, mainly through lifestyle changes.

The paper “An aged immune system drives senescence and ageing of solid organs” has been published in the journal Nature.

Scientists in Israel found a way to reverse cellular aging with century-old therapy

Telomeres on a chromosome. Credit: Wikimedia Commons.

All living creatures eventually wither and die. There’s no escaping death and taxes, they say. But that doesn’t mean aging can’t be slowed down. In fact, researchers at Tel Aviv University in Israel took it a step further, showing in a new study that weekly hyperbaric oxygen sessions reversed a key process known to be involved in cellular aging.

The caps on your chromosomes

Every day, every hour, every second one of the most important events in life is going on in your body—cells are dividing. Right now as you’re reading this sentence, somewhere cells are dividing, but each replication comes at a cost.

Telomeres cap and protect the ends of chromosomes from degradation, making sure our DNA gets copied properly when cells divide. Due to the way DNA replication is performed in eukaryotic cells (that’s us!), these telomeres shorten with each cellular replication. At some point, the telomeres, which you can envision as the caps of a shoelace, shorten to a critical limit. Just like a shoelace without a cap will detangle and ruin the fabric, so will severely shortened telomeres trigger the malfunction of cellular division, also known as senescence. In time, the accumulation of these senescent cells is believed to be one of the primary causes of aging.

Studies have linked shortened telomeres not only to aging but also to cancer. As such, the processes that regulate telomeres have been targeted by all sorts of experimental therapies meant to slow down aging. Of particular interest is an enzyme called telomerase, which seems to have the ability to regenerate lost sections of the telomere — at least it does so in tissues with a high turnover of new cells, such as the lining of the gut. Some groups look at telomerase gene therapy as being primarily a form of regenerative medicine. However, these therapies haven’t been validated due to the small number of participants so far.

In Israel, researchers led by Shair Efrati, a physician from the Faculty of Medicine and Sagol School of Neuroscience at Tel Aviv University, have taken a different route towards improving telomere health. Their therapy involves breathing pure oxygen in a pressurized chamber with pressure levels 1.5 to 3 times higher than average.

The procedure, known as hyperbaric oxygen therapy (HBOT), is by no means a novelty. For over a century it has been used to treat deep-sea divers suffering from decompression sickness or people who’ve been poisoned with carbon monoxide. 

In a clinical trial, 35 healthy adults aged 64 and older spent 90 minutes in a hyperbaric oxygen chamber, which saturated their blood with oxygen. The participants repeated this experience once a week over the course of three months.

Blood samples were collected before the treatment and during the trial at one-month intervals, as well as two weeks after the trial was over. Strikingly, by the end of the trial, the participants’ telomeres not only showed no shortening, they actually extended by 20%. The participants also experienced a significant drop in the number of senescent T helper cells, showing that the extended telomeres may be reversing some aging, the authors reported in the journal Aging.

As a caveat, the study’s main limitation is its small sample size. Furthermore, the duration of the therapy’s effect has yet to be determined in long-term follow-ups. But all things considered, these are promising results, showing that a relatively straightforward and readily available form of therapy could one day partially reverse aging — and perhaps even extend our lifespans.

Until such therapy is confirmed, the best thing you can do to preserve your telomeres is to have a healthy diet and exercise regularly.

Violent trauma makes children show signs of brain and genetic aging

Experiencing violence and abuse in early life can lead to faster aging later in life, both mentally and physically.

Image via Pixabay.

A new study from the American Psychological Association explains that experiencing trauma associated with violence early on impacts the way our bodies age throughout our lives. The researchers note this process happens in three indicators of biological aging: onset of puberty, the cellular aging process, and brain development.

Hard start

“Exposure to adversity in childhood is a powerful predictor of health outcomes later in life — not only mental health outcomes like depression and anxiety, but also physical health outcomes like cardiovascular disease, diabetes, and cancer,” said Katie McLaughlin, PhD, associate professor of psychology at Harvard University and senior author of the study.

“Experiencing violence can make the body age more quickly at a biological level, which may help to explain that connection.”

It’s not the first time researchers are looking into the link between a hard childhood and the speed of aging. However, they looked at several indicators of biological aging and different types of adversity together (such as violence, neglect, poverty, abuse. They found a link, but due to their structure, we couldn’t exactly tell what was causing what.

To get a clearer idea of what’s happening, the team performed a meta-analysis of over 80 studies (more than 116,000 participants in total) and teased apart threat-related adversity, such as abuse and violence, and deprivation-related adversity, such as neglect or poverty.

Children who experienced threat-related trauma were more likely to enter puberty early, the team explains, and show signs of accelerated cellular aging. One of the most telling signs of this latter type of aging was shortened telomeres, which are protective caps placed on the ends of DNA strands to keep them from breaking down. Children who experienced poverty or neglect, meanwhile, didn’t show early signs of aging.

The team then also looked at a further 25 studies (over 3,250 participants in total) to see how adversity in early life impacted later brain development. They did find it was associated with reduced cortical thickness, which is a sign of aging. Our cortices house most of our brain’s processing power and virtually all its higher functions, and are known to degrade as we get older.

However, the team did find that the exact type of adversity we experience as kids leads to thinning in a different area of the cortex. Trauma and violence affected the ventromedial prefrontal cortex in particular, which is involved in social and emotional processing. Deprivation was more often associated with thinning in the frontoparietal, default mode, and visual networks (involved in processing sensory information and other cognitive tasks).

As to why this process takes place, McLaughlin believed that maturing earlier could help ensure your survival in a violent, threat-filled environment. Alternatively, reaching puberty more early in such a setting would allow more people to possibly procreate. So they do have their uses — but in the modern world, they can lead to health complications later in life.

All of the studies worked with children and adolescents under age 18.

“The fact that we see such consistent evidence for faster aging at such a young age suggests that the biological mechanisms that contribute to health disparities are set in motion very early in life. This means that efforts to prevent these health disparities must also begin during childhood,” McLaughlin said.

The next step for the team is to investigate whether treatments aimed at children who have experienced trauma can help prevent or slow down this pattern of early aging.

The paper “Biological Aging in Childhood and Adolescence Following Experiences of Threat and Deprivation: A Systematic Review and Meta-Analysis” has been published in the journal Psychological Bulletin.

Researchers successfully reverse aging — in a lab dish

Researchers at the Stanford University School of Medicine have successfully de-aged human cells in a lab dish.

Image via Pixabay.

Carefully exposing human cells to Yamanaka factors, proteins involved in embryonic development that are used to transform adult cells into induced pluripotent stem (or iPS) cells, can reverse cellular aging. The authors report that old human cells in a lab dish treated with these proteins were nearly indistinguishable from fresh cells.

Ageback

“We are very excited about these findings,” said study co-author Thomas Rando, MD, Ph.D., the director of Stanford’s Glenn Center for the Biology of Aging. “My colleagues and I have been pursuing the rejuvenation of tissues since our studies in the early 2000s revealed that systemic factors can make old tissues younger.”

The authors explain that iPS cells produced from adult cells become “youthful” in the process. They wondered whether the process could be stopped mid-way, in order to make the cells more vigorous without causing them to revert back to a stem state. They found that it is possible, but the procedure hinges on carefully controlling the duration of exposure to Yamanaka factors. The team can use their approach to “promote rejuvenation in multiple human cell types,” explains Vittorio Sebastiano, Ph.D. the senior author of the study.

The factors gradually wipe a cell’s genetic material clean of the bits that differentiate them — those that make a skin cell and a blood cell different, for example — and revert them back to a younger state over the course of weeks. Instead, the team only allowed exposure to continue for a few days. They then compared the genetic activity of these cells with untreated cells from both elderly adults and younger participants.

The treated cells showed signs of age reversal after four days of exposure, the team explains, and their patterns of gene expression were similar to those seen in cells from younger participants. Treated cells appeared to be about one-and-a-half to three-and-a-half years younger on average than untreated cells from elderly people. The maximum values were three and a half years for skin cells and seven and a half years for cells lining blood vessels (when comparing methylation levels, a hallmark of cell aging).

“We saw a dramatic rejuvenation across all hallmarks but one in all the cell types tested,” Sebastiano said. “But our last and most important experiment was done on muscle stem cells. Although they are naturally endowed with the ability to self-renew, this capacity wanes with age. We wondered, Can we also rejuvenate stem cells and have a long-term effect?”

The team transplanted treated muscle cells back into old mice, and reported that they regained muscle strength comparable to that of younger mice. The process also helped cells from the cartilage of people (with and without osteoarthritis) reduce the secretion of inflammatory molecules, improve cellular function, and the cells’ ability to divide.

“Although much more work needs to be done, we are hopeful that we may one day have the opportunity to reboot entire tissues,” Sebastiano said. “But first we want to make sure that this is rigorously tested in the lab and found to be safe.”

The man who is ageing too fast

Credit: Moonassi for Mosaic.

Nobuaki Nagashima has Werner syndrome, which causes his body to age at super speed. This condition is teaching us more about what controls our genes, and could eventually help us find a way to slow ageing – or stop it altogether.

Nobuaki Nagashima was in his mid-20s when he began to feel like his body was breaking down. He was based in Hokkaido, the northernmost prefecture of Japan, where for 12 years he had been a member of the military, vigorously practising training drills out in the snow. It happened bit by bit – cataracts at the age of 25, pains in his hips at 28, skin problems on his leg at 30.

At 33, he was diagnosed with Werner syndrome, a disease that causes the body to age too fast. Among other things, it shows as wrinkles, weight loss, greying hair and balding. It’s also known to cause hardening of the arteries, heart failure, diabetes and cancer.Newsletter: 

I meet Nagashima under the white light of a Chiba University Hospital room, around 25 miles west of Tokyo. A grey newsboy cap covers his hairless head freckled with liver spots. His eyebrows are thinned to a few wisps. Black-rimmed glasses help with his failing eyesight, his hip joints – replaced with artificial ones after arthritis – ache as he stands to slowly walk across the room. These ailments you might expect to see in an 80-year-old. But Nagashima is just 43.

He tells me that he has been in and out of hospital ever since his diagnosis. That his deteriorating health forced him to leave the military. Nagashima has had five or six surgeries, from his toes to hips to eyes, to treat ageing-related ailments. He’s lost 15 kilograms since he was first diagnosed. He needs a walking stick to do a distance over a few metres, and has a temporary job at the City Hall, going to the office when his body will allow but working from home when it doesn’t.

He remembers driving home after his diagnosis, crying to himself. When he told his parents, his mother apologised for not giving birth to a stronger person. But his father told him that if he could endure this disease, he was indeed strong, and maybe scientists would learn from him, gaining knowledge that could help others.

Credit: Moonassi for Mosaic.

Apart from the X and Y sex chromosomes, we inherit two copies of every gene in our bodies – one from our mother and one from our father. Werner syndrome is what’s called an autosomal recessive disorder, meaning it only shows when a person inherits a mutated version of a gene called WRN from both parents.

Nagashima’s parents are ageing normally. They each have one functional copy of WRN, so their bodies don’t show any symptoms of the disease. But he was unfortunate to have received two mutated copies of WRN. His grandparents are still alive and as well as one might expect for a couple in their 90s, and the family are unaware of any other Werner cases in their family history.

WRN was discovered only in 1996, and since then there have been few examples of Werner. As of 2008, there were only 1,487 documented cases worldwide, with 1,128 of them in Japan.

Lest this seem like a uniquely Japanese condition, George Martin, co-director of the International Registry of Werner Syndrome at the University of Washington, thinks the number of actual cases globally is around seven times higher than the numbers recorded today. He says most cases around the world will not have come to the attention of any physicians or registries.

Credit: Moonassi for Mosaic.

The huge imbalance in Japanese cases he puts down to two factors. First, the mountains and islands of the Japanese landscape and the isolating effect that’s had on the population through history – people in more isolated regions in the past were more likely to end up having children with someone more similar to them genetically. A similar effect is seen in the Italian island of Sardinia, which also has a cluster of Werner cases. Second, the startling nature of the condition, and the higher frequency with which it appears in Japan (affecting an estimated one in a million people worldwide but one in 100,000 in Japan), means the Japanese medical system is more aware than most when Werner syndrome appears.

In Chiba University Hospital, they hold records of 269 clinically diagnosed patients in total, 116 of whom are still alive. One of them is Sachi Suga, who can only get around in a wheelchair. Her muscles are so weak she can no longer climb in and out of the bath, which makes it difficult to keep up the Japanese practice of ofuro, the ritual of relaxing each night in a deep tub of steaming hot water. She used to cook breakfast regularly for herself and her husband, but now she cannot stand at a stove for more than a minute or two at a time. She’s resorted to preparing quicker-to-make miso soup the night before, which he eats before leaving for work at 5.30am.

Waif-like in a short black wig, Suga has tiny wrists as delicate as glass, and she speaks to me in a hoarse, throaty whisper. She tells me of the home aid worker who visits three times a week to help wrap her ulcer-covered legs in bandages. She has terrible back and leg pain. “It hurt so much, I wanted my legs to be cut off.” Yet on the positive side, the 64-year-old has long surpassed the average life expectancy of around 55 for people with Werner syndrome.

Only a handful of people with Werner currently attend Chiba. Recently, they started a support group. “Once our conversation started, I forgot about the pain completely,” says Suga. Nagashima says the meetings often end with the same question: “Why do I have this disease?”

If you were to unravel the 23 pairs of chromosomes in one of your cells you would end up with about two metres of DNA. That DNA is folded up into a space about a 10,000th of that distance across – far more compacted than even the tightest origami design. This compacting happens with help from proteins called histones.

DNA, and the histones that package it up, can acquire chemical marks. These don’t change the underlying genes, but they do have the power to silence or to amplify a gene’s activity. Where the marks are put or what form they take seems to be influenced by our experiences and environment – in response to smoking or stress, for instance. Some seem to be down to random chance, or the result of a mutation, as in cancer. Scientists call this landscape of markings the epigenome. We do not know yet exactly why our cells add these epigenetic marks, but some of them seem to be connected to ageing.

Steve Horvath, professor of human genetics and biostatistics at the University of California, Los Angeles, has used one type of these, called methylation marks, to create an “epigenetic clock” that, he says, looks beyond the external signs of ageing like wrinkles or grey hair, to more accurately measure how biologically old you are. The marks can be read from blood, urine, organ or skin tissue samples.

Horvath’s team analysed blood cells from 18 people with Werner syndrome. It was as if the methylation marking was happening on fast-forward: the cells had an epigenetic age notably higher than those from a control group without Werner.

Nagashima’s and Suga’s genetic information is part of a database held by Chiba University. There is also a Japan-wide database of Werner syndrome and the International Registry at the University of Washington. These registries are providing researchers with insights into how our genes work, how they interact with the epigenome, and how that fits with ageing as a whole.

Scientists now understand that WRN is key to how the whole cell, how all our DNA works – in reading, copying, unfolding and repairing. Disruption to WRN leads to widespread instability throughout the genome. “The integrity of the DNA is altered, and you get more mutations… more deletions and aberrations. This is all over the cells,” says George Martin. “Big pieces are cut out and rearranged.” The abnormalities are not just in the DNA but in the epigenetic marks around it too.

The million-dollar question is whether these marks are imprints of diseases and ageing or whether the marks cause diseases and ageing – and ultimately death. And if the latter, could editing or removing epigenetic marks prevent or reverse any part of ageing or age-related disease?

Before we can even answer that, the fact is, we know relatively little about the processes through which epigenetic marks are actually added and why. Horvath sees methylation marks as like the face of a clock, not necessarily the underlying mechanism that makes it tick. The nuts and bolts may be indicated by clues like the WRN gene, and other researchers have been getting further glimpses beneath the surface.

In 2006 and 2007, Japanese researcher Shinya Yamanaka published two studies which found that putting four specific genes – now called Yamanaka factors – into any adult cell could rewind it to an earlier, embryonic state, a stem cell, from which it could then be turned into any other type of cell. This method, which earned Yamanaka the Nobel Prize, has become a mainspring for stem cell studies. But what made this all the more interesting was that it completely reset the epigenetic age of the cells to a prenatal stage, erasing the epigenetic marks.

Researchers replicated Yamanaka’s experiments in mice with a condition called Hutchinson–Gilford progeria syndrome, which has similar symptoms to Werner but only affects children (Werner is sometimes called adult progeria). Remarkably, the mice rejuvenated briefly, but they died within a couple of days. Totally reprogramming the cells had also led to cancer and loss of the cells’ ability to function.

Then in 2016, scientists at the Salk Institute in California engineered a way to partially rewind the cells of mice with progeria using a lower dose of the Yamanaka factors for a shorter period. The premature ageing slowed down in these mice. They not only looked healthier and livelier than progeria mice who hadn’t had the treatment, but their cells were also found to have fewer epigenetic marks. Moreover, they lived 30 per cent longer than the untreated mice. When the researchers applied this same treatment to normally ageing mice, their pancreases and muscles also rejuvenated.

Separately, the same scientists are also using gene editing technology on mice to add or subtract other epigenetic marks and see what happens. They’re also trying to modify the histone proteins to see if that can alter genes’ activity. Some of these techniques have already shown results in reversing diabetes, kidney disease and muscular dystrophy in mice. The team are now trying similar experiments on rodents to see if they can reduce the symptoms of arthritis and Parkinson’s disease.

The big question remains: is the disappearance of the epigenetic marks related to the reversal of cell development – and possibly the ageing of the cell – or an unrelated side-effect? Scientists are still trying to understand how changes in epigenetic marks relate to ageing, and how Yamanaka factors are able to reverse age-related conditions.

Horvath says that, from an epigenetic point of view, there are clear commonalities in ageing across many regions of the body. Epigenetic ageing in the brain is similar to that of the liver or the kidney, showing similar patterns of methylation marks. When you look at it in terms of these marks, he says, “ageing is actually rather straightforward, because it’s highly reproducible in different organs”.

There’s a feverishness around the idea of resetting or reprogramming the epigenetic clock, Horvath tells me. He sees huge potential in all of it, but says it has the feel of a gold rush. “Everybody has a shovel in their hand.”

Jamie Hackett, a molecular biologist at the European Molecular Biology Laboratory in Rome, says the excitement comes from the suggestion that you can have an influence over your genes. Previously there was a fatalistic sense of being stuck with what you are given, and nothing you can do about it.

Back in the Chiba hospital room, Nagashima removes one of his high-top sneakers, which he has cushioned with insoles to make walking more bearable.

He tells me about his former girlfriend. They had wanted to marry. She was understanding after his diagnosis and even took a genetic test so they could be sure they would not pass the condition on to their kids. But when her parents discovered his condition, they disapproved. The relationship ended.Newsletter: 

He has a new girlfriend now. He wants to make her his life partner, he tells me, but to do so he must get up the courage to ask for her parents’ permission.

Nagashima slips down a brown sock, revealing a white bandage wrapped around the sole of his swollen foot and ankles. Beneath, his skin is raw, revealing red ulcers caused by his disease. “Itai,” he says. It hurts. Then he smiles. “Gambatte,” he says – I will endure.

Nobuaki Nagashima was in his mid-20s when he began to feel like his body was breaking down. He was based in Hokkaido, the northernmost prefecture of Japan, where for 12 years he had been a member of the military, vigorously practising training drills out in the snow. It happened bit by bit – cataracts at the age of 25, pains in his hips at 28, skin problems on his leg at 30.

At 33, he was diagnosed with Werner syndrome, a disease that causes the body to age too fast. Among other things, it shows as wrinkles, weight loss, greying hair and balding. It’s also known to cause hardening of the arteries, heart failure, diabetes and cancer. Newsletter: 

I meet Nagashima under the white light of a Chiba University Hospital room, around 25 miles west of Tokyo. A grey newsboy cap covers his hairless head freckled with liver spots. His eyebrows are thinned to a few wisps. Black-rimmed glasses help with his failing eyesight, his hip joints – replaced with artificial ones after arthritis – ache as he stands to slowly walk across the room. These ailments you might expect to see in an 80-year-old. But Nagashima is just 43.

He tells me that he has been in and out of hospital ever since his diagnosis. That his deteriorating health forced him to leave the military. Nagashima has had five or six surgeries, from his toes to hips to eyes, to treat ageing-related ailments. He’s lost 15 kilograms since he was first diagnosed. He needs a walking stick to do a distance over a few metres, and has a temporary job at the City Hall, going to the office when his body will allow but working from home when it doesn’t.

He remembers driving home after his diagnosis, crying to himself. When he told his parents, his mother apologised for not giving birth to a stronger person. But his father told him that if he could endure this disease, he was indeed strong, and maybe scientists would learn from him, gaining knowledge that could help others.

Apart from the X and Y sex chromosomes, we inherit two copies of every gene in our bodies – one from our mother and one from our father. Werner syndrome is what’s called an autosomal recessive disorder, meaning it only shows when a person inherits a mutated version of a gene called WRN from both parents.

Nagashima’s parents are ageing normally. They each have one functional copy of WRN, so their bodies don’t show any symptoms of the disease. But he was unfortunate to have received two mutated copies of WRN. His grandparents are still alive and as well as one might expect for a couple in their 90s, and the family are unaware of any other Werner cases in their family history. WRN was discovered only in 1996, and since then there have been few examples of Werner. As of 2008, there were only 1,487 documented cases worldwide, with 1,128 of them in Japan.

Lest this seem like a uniquely Japanese condition, George Martin, co-director of the International Registry of Werner Syndrome at the University of Washington, thinks the number of actual cases globally is around seven times higher than the numbers recorded today. He says most cases around the world will not have come to the attention of any physicians or registries.

The huge imbalance in Japanese cases he puts down to two factors. First, the mountains and islands of the Japanese landscape and the isolating effect that’s had on the population through history – people in more isolated regions in the past were more likely to end up having children with someone more similar to them genetically. A similar effect is seen in the Italian island of Sardinia, which also has a cluster of Werner cases. Second, the startling nature of the condition, and the higher frequency with which it appears in Japan (affecting an estimated one in a million people worldwide but one in 100,000 in Japan), means the Japanese medical system is more aware than most when Werner syndrome appears.

In Chiba University Hospital, they hold records of 269 clinically diagnosed patients in total, 116 of whom are still alive. One of them is Sachi Suga, who can only get around in a wheelchair. Her muscles are so weak she can no longer climb in and out of the bath, which makes it difficult to keep up the Japanese practice of ofuro, the ritual of relaxing each night in a deep tub of steaming hot water. She used to cook breakfast regularly for herself and her husband, but now she cannot stand at a stove for more than a minute or two at a time. She’s resorted to preparing quicker-to-make miso soup the night before, which he eats before leaving for work at 5.30am.

Waif-like in a short black wig, Suga has tiny wrists as delicate as glass, and she speaks to me in a hoarse, throaty whisper. She tells me of the home aid worker who visits three times a week to help wrap her ulcer-covered legs in bandages. She has terrible back and leg pain. “It hurt so much, I wanted my legs to be cut off.” Yet on the positive side, the 64-year-old has long surpassed the average life expectancy of around 55 for people with Werner syndrome.

Only a handful of people with Werner currently attend Chiba. Recently, they started a support group. “Once our conversation started, I forgot about the pain completely,” says Suga. Nagashima says the meetings often end with the same question: “Why do I have this disease?”

His mother apologised for not giving birth to a stronger person. But his father told him that if he could endure this disease, he was indeed strong.

If you were to unravel the 23 pairs of chromosomes in one of your cells you would end up with about two metres of DNA. That DNA is folded up into a space about a 10,000th of that distance across – far more compacted than even the tightest origami design. This compacting happens with help from proteins called histones.

DNA, and the histones that package it up, can acquire chemical marks. These don’t change the underlying genes, but they do have the power to silence or to amplify a gene’s activity. Where the marks are put or what form they take seems to be influenced by our experiences and environment – in response to smoking or stress, for instance. Some seem to be down to random chance, or the result of a mutation, as in cancer. Scientists call this landscape of markings the epigenome. We do not know yet exactly why our cells add these epigenetic marks, but some of them seem to be connected to ageing.

Steve Horvath, professor of human genetics and biostatistics at the University of California, Los Angeles, has used one type of these, called methylation marks, to create an “epigenetic clock” that, he says, looks beyond the external signs of ageing like wrinkles or grey hair, to more accurately measure how biologically old you are. The marks can be read from blood, urine, organ or skin tissue samples.

Horvath’s team analysed blood cells from 18 people with Werner syndrome. It was as if the methylation marking was happening on fast-forward: the cells had an epigenetic age notably higher than those from a control group without Werner.

The million-dollar question is whether these marks are imprints of diseases and ageing or whether the marks cause diseases and ageing – and ultimately death.

Nagashima’s and Suga’s genetic information is part of a database held by Chiba University. There is also a Japan-wide database of Werner syndrome and the International Registry at the University of Washington. These registries are providing researchers with insights into how our genes work, how they interact with the epigenome, and how that fits with ageing as a whole.

Scientists now understand that WRN is key to how the whole cell, how all our DNA works – in reading, copying, unfolding and repairing. Disruption to WRN leads to widespread instability throughout the genome. “The integrity of the DNA is altered, and you get more mutations… more deletions and aberrations. This is all over the cells,” says George Martin. “Big pieces are cut out and rearranged.” The abnormalities are not just in the DNA but in the epigenetic marks around it too.

The million-dollar question is whether these marks are imprints of diseases and ageing or whether the marks cause diseases and ageing – and ultimately death. And if the latter, could editing or removing epigenetic marks prevent or reverse any part of ageing or age-related disease?

Before we can even answer that, the fact is, we know relatively little about the processes through which epigenetic marks are actually added and why. Horvath sees methylation marks as like the face of a clock, not necessarily the underlying mechanism that makes it tick. The nuts and bolts may be indicated by clues like the WRN gene, and other researchers have been getting further glimpses beneath the surface.

In 2006 and 2007, Japanese researcher Shinya Yamanaka published two studies which found that putting four specific genes – now called Yamanaka factors – into any adult cell could rewind it to an earlier, embryonic state, a stem cell, from which it could then be turned into any other type of cell. This method, which earned Yamanaka the Nobel Prize, has become a mainspring for stem cell studies. But what made this all the more interesting was that it completely reset the epigenetic age of the cells to a prenatal stage, erasing the epigenetic marks.

Researchers replicated Yamanaka’s experiments in mice with a condition called Hutchinson–Gilford progeria syndrome, which has similar symptoms to Werner but only affects children (Werner is sometimes called adult progeria). Remarkably, the mice rejuvenated briefly, but they died within a couple of days. Totally reprogramming the cells had also led to cancer and loss of the cells’ ability to function.

Then in 2016, scientists at the Salk Institute in California engineered a way to partially rewind the cells of mice with progeria using a lower dose of the Yamanaka factors for a shorter period. The premature ageing slowed down in these mice. They not only looked healthier and livelier than progeria mice who hadn’t had the treatment, but their cells were also found to have fewer epigenetic marks. Moreover, they lived 30 per cent longer than the untreated mice. When the researchers applied this same treatment to normally ageing mice, their pancreases and muscles also rejuvenated.

Separately, the same scientists are also using gene editing technology on mice to add or subtract other epigenetic marks and see what happens. They’re also trying to modify the histone proteins to see if that can alter genes’ activity. Some of these techniques have already shown results in reversing diabetes, kidney disease and muscular dystrophy in mice. The team are now trying similar experiments on rodents to see if they can reduce the symptoms of arthritis and Parkinson’s disease.

The big question remains: is the disappearance of the epigenetic marks related to the reversal of cell development – and possibly the ageing of the cell – or an unrelated side-effect? Scientists are still trying to understand how changes in epigenetic marks relate to ageing, and how Yamanaka factors are able to reverse age-related conditions.

Horvath says that, from an epigenetic point of view, there are clear commonalities in ageing across many regions of the body. Epigenetic ageing in the brain is similar to that of the liver or the kidney, showing similar patterns of methylation marks. When you look at it in terms of these marks, he says, “ageing is actually rather straightforward, because it’s highly reproducible in different organs”.

There’s a feverishness around the idea of resetting or reprogramming the epigenetic clock, Horvath tells me. He sees huge potential in all of it, but says it has the feel of a gold rush. “Everybody has a shovel in their hand.”

Jamie Hackett, a molecular biologist at the European Molecular Biology Laboratory in Rome, says the excitement comes from the suggestion that you can have an influence over your genes. Previously there was a fatalistic sense of being stuck with what you are given, and nothing you can do about it.

The excitement comes from the suggestion that you can have an influence over your genes.

Back in the Chiba hospital room, Nagashima removes one of his high-top sneakers, which he has cushioned with insoles to make walking more bearable.

He tells me about his former girlfriend. They had wanted to marry. She was understanding after his diagnosis and even took a genetic test so they could be sure they would not pass the condition on to their kids. But when her parents discovered his condition, they disapproved. The relationship ended.

He has a new girlfriend now. He wants to make her his life partner, he tells me, but to do so he must get up the courage to ask for her parents’ permission.

Nagashima slips down a brown sock, revealing a white bandage wrapped around the sole of his swollen foot and ankles. Beneath, his skin is raw, revealing red ulcers caused by his disease. “Itai,” he says. It hurts. Then he smiles. “Gambatte,” he says – I will endure.

This article first appeared on Mosaic and is republished here under a Creative Commons licence.

You’re really only as old as you feel — or rather, as you think

Being more physically active and having a firm mental control over your life could, in fact, make you younger, a new study suggests.

How you choose to live your life directly affects how you age. Simple things, like opting for a healthy diet and staying physically active

, have been repeatedly shown to not only improve your health but also to delay aging. In a more subtle way, the same thing goes for your mind — staying mentally active is a great way to combat many of the downsides that come with old age.

Essentially, doing these things helps you feel younger, which in turn can rejuvenate you.

Researchers enlisted 116 older adults (ages 60 to 90) and 106 younger adults (ages 18 to 36) and asked them to fill out surveys each day for nine days. They were asked to agree or disagree with statements about how in control they felt during each particular day, such as “In the past 24 hours, I had quite a bit of influence on the degree to which I could be involved in activities.” They were also asked to state how old they felt each day.

Intriguingly, the results varied significantly from day to day.

“Research suggests that a younger subjective age, or when people feel younger than their chronological age, is associated with a variety of positive outcomes in older individuals, including better memory performance, health and longevity,” said presenter Jennifer Bellingtier, PhD, of Friedrich Schiller University. “Our research suggests that subjective age changes on a daily basis and older adults feel significantly younger on days when they have a greater sense of control.”

Both the younger and the older adults exhibited these day-to-day differences, but there was an important difference: while the perceived level of self-control and subjective age was unrelated in the younger group, the two were strongly correlated in the older group.

“Shaping the daily environment in ways that allow older adults to exercise more control could be a helpful strategy for maintaining a youthful spirit and overall well-being,” said Bellingtier.

This, in turn, suggests that the subjective, self-perceived age could be improved through simple interventions, as Bellingtier himself suggests.

“For example, some interventions could be formal, such as a regular meeting with a therapist to discuss ways to take control in situations where individuals can directly influence events, and how to respond to situations that they cannot control. Smartphone apps could be developed to deliver daily messages with suggestions for ways to enhance control that day and improve a person’s overall feeling of control,” said Bellingtier. “An intervention could also be something as simple as giving nursing home residents the opportunity to make more choices in their daily lives so that they can exercise more control.”

Things get even better. When people feel younger, they do things that actually help them stay younger, like physical activity or things that make them happy. Like a self-fulfilling prophecy, feeling younger can actually make you younger.

However, while the researchers’ interpretation seems valid, it’s not a guarantee just yet. The sample size was quite small, and they need to replicate their findings on a much broader sample size, says Matthew Hughes, PhD, University of North Carolina, Greensboro, who was also involved in the study. It’s really good news, but it still needs to be validated.

“As this was part of a pilot study, our sample size was small,” he said. “While the results suggest that walking may contribute to feeling younger, further research with a larger sample in a more controlled setting is needed to confirm.”

Results were presented in the American Psychological Association, in Washington, D.C., and have not yet been peer-reviewed.

Cutting calories delays ageing, new study shows

A new comprehensive study has shown that reducing caloric intake slows down metabolism. Researchers believe the findings indicate that a low-calorie diet could extend lifespan and prolong health in old age.

Via Pixabay/Divily

Previous studies on animals with short lifespans — such as worms, mice, and flies — have shown that reducing calorie intake might slow down metabolism and prolong life. However, demonstrating this effect on humans and other animals with long lifespans has proven quite difficult.

Researchers studied some of the people who participated in the multi-center trial CALERIE (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy), sponsored by the US National Institutes of Health. Scientists observed the effects of restricting calories for 2 years on metabolism in over 200 healthy, non-fat adult participants.

“The CALERIE trial has been important in addressing the question of whether the pace of aging can be altered in humans,” says Rozalyn Anderson, who studies aging at the University of Wisconsin–Madison. She leads one of two large, independent studies on calorie restriction in rhesus monkeys. “This new report provides the most robust evidence to date that everything we have learnt in other animals can be applied to ourselves.”

The latest paper, which was published on March 22nd in the journal Cell Metabolism, monitored 53 CALERIE participants recruited at the Pennington Biomedical Research Center in Baton Rouge, Louisiana. Researchers were able to track how the participants used energy with unprecedented precision thanks to state-of-the-art metabolic chambers —  small, hotel-like sealed rooms that measure oxygen and carbon dioxide concentrations every 60 seconds. Researchers calculated the ratio between the two gases and then analyzed occupants’ urinary nitrogen, indicating whether the occupant is burning fat, carbohydrate or protein.

Participants, with ages between 21 and 50, were randomly separated into two groups: the 34 people in the experimental group reduced their calorie consumption by an average of 15%, while the 19 people in the control group ate as usual. Next, researchers tested the participants annually to record overall metabolism and biological markers of aging, including damage associated with oxygen free radicals released during metabolism. At the end of the trial, participants spent 24 hours in the metabolic chamber.

Researchers discovered that the people who had dieted used energy much more efficiently while sleeping than the control group. Their base metabolism had essentially slowed down. In consequence, people in the experimental group lost an average of 9 kilos individually. All other measurements showed a reduced metabolic rate and fewer signs of aging.

“The Rolls-Royce of a human longevity study would carry on for many decades to see if people do actually live longer,” says Pennington physiologist Leanne Redman, the lead author of the latest study.

Low-calorie diets have previously been shown to extend life in different species, such as the short lifespan worm Caenorhabditis elegans, and in the fly Drosophila melanogaster. Following studies also revealed that mice with restricted diets can live up to 65% longer than mice allowed to eat freely. In addition, studies on monkeys suggest longer survival and reduced signs of aging.

Redman wants to repeat the study combining moderate calorie restriction with a diet rich in antioxidants to monitor oxidative stress, or with a drug such as resveratrol, which mimics key aspects of calorie restriction.

If researchers demonstrate the causality between caloric reduction and longer lives in humans, could you stick to such a diet?

Childbirth can make women’s cells age faster than smoking or obesity

We all know that pregnancy and childbirth change women’s minds and bodies. A new study has found that women who give birth can age very fast, genetically speaking. But how?

Via Pixabay/marvelmozhko

Researchers collected DNA data from 1,505 different women from the US, with ages ranging from twenty to forty-four and discovered that having children significantly altered genetic markers of aging — telomeres, to be exact.

Telomeres are repetitive DNA fragments found at each end of the chromosomes, which protects them from deterioration or from fusion with neighboring chromosomes. At birth, our telomeres are long, but with each cell replication, telomeres grow shorter. Thus, telomere length decreases from birth to death and is considered a marker of aging. Shorter telomeres are correlated with outcomes like cancer, heart disease, and cognitive decline. Another cause of telomere shortening is stress,

Epidemiologist Anna Pollack from George Mason University and her team analyzed data from the National Health and Nutrition Examination Survey (NHANES) – one of the largest cross-sectional studies charting the wellness of people in the US.

Researchers analyzed data collected between the years 1999–2002, a period in which the survey included telomere measurements, and discovered something unsettling.

Once the team had adjusted for things like age, ethnicity, education, and smoking status, they discovered that women who had given birth to at least one child had telomeres that were 4.2 percent shorter on average than those of women who had not borne children.

Researchers explain that this percentage translates to around 11 years of rapid cellular aging. Compared to smoking (a cost of 4.6 years of cellular aging) and obesity (8.8 years), motherhood seems to be the champion of accelerated  DNA aging.

The study also revealed that the more children you have, the more your telomeres shrink.

“We found that women who had five or more children had even shorter telomeres compared to those who had none, and relatively shorter relative to those who had one, two, three or four, even,” Pollack told Newsweek.

The authors attributed telomere shortening to the stress accompanying having children, but they are not yet entirely sure of the cause. This study was purely observational, showing only a correlation between the two.

A 2016 study that analyzed telomere size in Mayan communities in Guatemala found that women in the community that had more surviving children had longer telomeres, suggesting that having children could actually protect women from cellular aging. Researchers believe that Mayan communities give more social support to their mothers than the US does — a great deal of stress being involved in the upbringing of the US kids.

“Anecdotally, just chatting with my friends who have children, we all do feel that having kids has aged us,” Pollack said to Newsweek. “But scientifically, this does fit with what we understand pretty well. We know that having kids is associated with a higher risk of heart disease and diabetes. And some large studies have linked telomere length to mortality risk and risks of other major diseases.”

Of course, having a child doesn’t mean you literally age 11 years. The authors write that their dataset lacked information on social factors, stress and fertility status, which may help explain these findings. With only two other previous studies regarding this matter being published, this paper‘s findings should be interpreted with caution, the authors warn.

Naked mole-rats live extremely long lives and do not age, study finds

Biology’s ‘ugly duckling’ cannot cease to amaze us. Researchers have analyzed a large trove of data on historical naked mole-rat lifespan and discovered something truly amazing. Not only do the naked mole-rats live 5 times longer than a similar-sized mammal, but they also do not show any signs of aging whatsoever.

Credits: Flickr/Tim Evanson

Naked mole-rats’ superpowers

Mole-rats are astonishing creatures. What they lack in aesthetics they make up in superpowers: they’re immune to cancer, don’t feel pain, can switch from being cold-blooded to warm-blooded, can run backward as fast as forward, and can live in extremely low oxygen conditions, their brains being capable of surviving without oxygen for up to five hours. Also, their front teeth grow out in front of their mouths.

Their behavior is even weirder. The African mole-rat, scientifically known as Heterocephalus galber, exhibits eusociality. This means that mole-rats social life is more like an ant’s than that of a typical mammal. Only the queen and one to three chosen males are fertile and are in charge of reproduction. The other members of the colony (usually consisting of almost 300 mole-rats) are in charge of food gathering, burrow security, digging tunnels, tunnel maintenance, some of them even being nannies.

If the queen dies, any other unfertile female can be crowned. The regular working mole-rat is unfertile but can turn on the reproduction function if needed. Some biologists suggest that this could be one of the reasons mole-rats live such long lives, they believe that the tiny creatures are just waiting patiently to have offsprings.

Forever young

Lead researcher Rochelle Buffenstein has studied naked mole-rats for over 30 years and has collected a huge amount data on them, including lifespan. The comparative biologist, who works for Google’s anti-aging company Calico, was completely amazed by the results. She gathered data from over 3,000 specimens from her lab and discovered that the Gompertz-Makeham law, a mathematical equation that relates aging to mortality, doesn’t apply to mole-rats.

Basically, the law says that the risk of dying rises exponentially with age; in humans, for example, it doubles roughly every 8 years after the age of 30. This theory successfully applies to most animals, especially to mammals, but apparently not to our rodent super-heroes. A naked mole-rat’s daily risk of dying is a little more than one in 10,000, even after reaching sexual maturity at 6 months, and stays the same throughout their lives, sometimes even going down a little bit more. If this isn’t unfathomable, I truly don’t know what is.

“To me this is the most exciting data I’ve ever gotten,” says Buffenstein. “It goes against everything we know in terms of mammalian biology.”

Different studies have shown that the rodent possesses certain aging-protective qualities like very active DNA repair and high levels of chaperones, which are helper proteins that support other molecules in folding correctly. Buffenstein thinks that the almost-cute animal focusses more on keeping what it already has, rather than accumulate damage.

Adding the small number of predators, high resistance to cancer and friendly behavior to the equation, we might understand why these animals have such a small risk of dying prematurely.The oldest mole-rat in captivity is 35 years old. A mouse its size lives no longer than 4 years.

But anti-aging is something else, completely. For a change, the mole-rats’ blood vessels retain their elasticity, and the queens do not enter menopause and are still able to breed even at the age of thirty.

“Our research demonstrates that naked mole rats do not age in the same manner as other mammals, and in fact show little to no signs of ageing, and their risk of death does not increase even at 25 times past their time to reproductive maturity,” Buffenstein said.

“These findings reinforce our belief that naked mole rats are exceptional animals to study to further our understanding of the biological mechanisms of longevity.”

The paper was published Jan 24, 2018, in the journal eLIFE.

rejuvenation

New therapy rejuvenates old cells in the lab, which now behave like young cells

A novel method developed at the University of Exeter rejuvenates old cells cultured in the lab, causing them to behave more like young cells. It took only a couple of hours after the treatment was applied to the old cells for these to start dividing and growing larger telomers. The technique could lead to a new class of therapies meant to help people age not only longer but healthier, too.

rejuvenation

Credit: Pixabay.

As we age, the cells in the body quietly but surely enter senescence, meaning they cease to divide. These cells are still alive, it’s just that they stop functioning properly. For instance, a class of genes called splicing factors are progressively switched off as humans age.

Splicing factors are crucial proteins that help gene perform their full range of functions. A single gene can code multiple instructions for the body, such as whether or not to grow new blood vessels, and the splicing factors are the decision makers that choose which message takes priority. Because splicing factors become increasingly inefficient with age, the body ends up losing its ability to respond properly to the many challenges in the environment.

Senescent cells can be found in copious amounts in the organs of the elderly. They’re one of the main reasons why most people over age 85 have experienced some sort of chronic illness. Switched off splicing factors make people more vulnerable to cancer stroke, and heart disease as they age.

Led by Professor Lorna Harries, researchers at the University of Exeter experimented with resveratrol analogs on old cells in the lab. These chemicals are based on a substance naturally found in red wine, dark chocolate, red grapes, and blueberries.

Credit: BMC Cell Biology.

Credit: BMC Cell Biology.

Strikingly, within hours of coming into contact with the compounds, the splicing factors in the cells switched back on. The cells showed signs of rejuvenation as they started dividing, essentially behaving like young cells. What’s more, the cells’ telomeres — the caps on the ends of the chromosomes that shorten as we age —  are now longer, as they are in young cells

“At present, the precise mechanisms behind these observations are unclear, but may involve both the restoration of a more ‘youthful’ pattern of alternative splicing, and also effects of specific splicing factors on telomere maintenance,” the authors conclud in their paper.

“This demonstrates that when you treat old cells with molecules that restore the levels of the splicing factors, the cells regain some features of youth,” Harries said.

The findings published in the journal BMC Cell Biology could potentially lead to therapies that help people age healthier, with less risk of developing chronic disease and by delaying the usual degenerating effects of old age.

“When I saw some of the cells in the culture dish rejuvenating I couldn’t believe it. These old cells were looking like young cells. It was like magic,” said co-author Eva Latorre, Research Associate at the University of Exeter. “I repeated the experiments several times and in each case the cells rejuvenated. I am very excited by the implications and potential for this research.”

Shown here are two aged rats. The one in the back received a peptide treatment which destroys senescent cells while the one in the front didn't. The latter mouse is in poor health as evidenced by the missing fur. Credit: Peter de Keizer

Drug reverses aging in mice. The rodents saw increased stamina, better organ function, and restored fur

Dutch researchers from the Erasmus University Medical Center boast promising results with a new drug meant to reverse the effects of aging.Tests performed on mice suggests the drug is effective at restoring stamina, coat of fur, and even some organ function.

Shown here are two aged rats. The one in the back received a peptide treatment which destroys senescent cells while the one in the front didn't. The latter mouse is in poor health as evidenced by the missing fur. Credit: Peter de Keizer

Shown here are two aged rats. The one in the back received a peptide treatment which destroys senescent cells while the one in the front didn’t. The latter mouse is in poor health as evidenced by the missing fur. Credit: Peter de Keizer

As we age, some cells begin to change their internal structure and ability to keep homeostasis. One component of aging is the damage caused by senescent cells, which are cells which have stopped dividing but which have not destroyed themselves as they should have following programmed cell death. Senescent cells secrete abnormally large amounts of some proteins that are harmful to their neighbours, stimulating excessive growth and degrading normal tissue architecture. These cells have also been associated with cancer and release chemicals that cause inflammation.

What the drug does is it effectively flushes out senescent cells out of the body by disrupting the chemical balance within them. The team led by Dr Peter de Keizer had previously made three fail attempts but were lucky the fourth time around, they report in the journal Cell.

The drug was injected into mice which were genetically modified to age very rapidly as well as in mice that were artificially aged through chemotherapy. Their equivalent age in human years was 90 and the drug was administered three times a week for nearly a year. At the end of the experiments, the rejuvenating effect of the therapy was clear. Age-related loss of fur, poor kidney function, and frailty became reversed.There were no apparent side effects, but that doesn’t mean they’re totally absent. “Mice don’t talk,” Keizer said which is why his team is planning human trials.

The drug itself is a peptide which took nearly four years of trial and error to reach its final form. It works by blocking the ability of a protein implicated in senescence, FOXO4, to tell another protein, p53, not to cause the cell to self-destruct. By interfering with this cross-talk, the senescent cells essentially perform suicide. “Only in senescent cells does this peptide cause cell death,” Kaizer said.

Improvements showed at different times over the course of the treatment. Aged mice that presented patches of missing fur began to grow their coats back after ten days. Fitness levels started to improve after three weeks as tests showed older mice could run twice as far as their counterparts who did not receive the treatment. A month later, the old mice showed improvements in healthy kidney function.

Senescent cells have some beneficial roles in the body. Killing off too many of these cells can trigger cascading complications that can lead to tumour formation. Senescent cells also foster wound healing. With this in mind, a similar treatment meant for humans has to be very well refined else the therapy could end up doing more harm than good. So, it seems very likely that a ‘magic’ age-reversal pill bought over the counter is decades away but it’s exciting to hear about all of these developments now.

horvath genetics

Science explains why some people age faster and die younger regardless of lifestyle

horvath genetics

Credit: Steve Horvath

Once each human comes into this world, we’re given a clock whose tick-tock beats to the tune of life. This clock is unique to every person because the pace with which it’s ticking is different, as the clock is wound up by epigenetic changes in the genome. This is the metaphorical conclusion of a groundbreaking study published by biostatisticians at the University of California, Los Angeles. Simply put, some people are destined to biologically age faster than others, even when all things like smoking, eating healthy or exercising are equal. There’s reason to believe these epigenetic changes can be reversed, with far-reaching implications for research in longevity.

Can we wind back the clock?

Steve Horvath, the lead researcher of the study from UCLA, and colleagues, analyzed blood samples collected from 13,000 people, sequenced their genomes, then studied the methyl levels at 353 specific sites. Previously, Horvath’s group showed that the methyl levels of these sites rise and fall according to a specific pattern as the person ages and this pattern is consistent across the whole population.

When the scientists completed their survey, about 2,700 of the initial participants had died. Things like smoking, blood pressure, and body weight were still the best predictive factors for life expectancy but the aging rate was also significant. In other words, some people could live the same healthy lifestyles but die younger or older simply because their internal biological clock is ticking faster or slower.

“Our findings show that the epigenetic clock was able to predict the lifespans of Caucasians, Hispanics and African-Americans in these cohorts, even after adjusting for traditional risk factors like age, gender, smoking, body-mass index and disease history,” said Brian Chen, the study’s first author and a postdoctoral fellow at the National Institute on Aging.

The team found that for 5 percent of the population that ages the fastest, there’s a 50 percent greater average risk of dying at any age. For instance, Horvath mentions a fictitious case study involving two 60-year-old men. Pete is ranked in the top 5 percent of the population that ages the fastest while Joe is classed in the 5 percent of the population that ages the slowest. If both lead stressful lives and smoke tobacco, then Pete has   a 75% chance of dying in the next 10 years compared to a 46% chance for Joe.

Horvath, who is 48 years old, took his own test and found he’s actually five years older, biologically speaking.

The findings published in the journal Aging partially explain why men on average die younger than women. In the U.S., life expectancy for women is 81.2 years; for males, it’s 76.4 years. Horvath says that even by age 5 differences in aging rate can be observed. By the time people are 40 years old, the biological age gap opens up to about 1 to 2 years.

“We must find interventions that prolong healthy living by five to 20 years. We don’t have time, however, to follow a person for decades to test whether a new drug works.” Horvath said. “The epigenetic clock would allow scientists to quickly evaluate the effect of anti-aging therapies in only three years.”

If you’re good with data sets and had your DNA sequenced in the past, there’s a tutorial written by Professor Horvath that will teach you how to calculate your biological age.

hourglass aging

New research challenges aging consensus by reversing mitochondrial anomalies in 97-year-old cells

A team led by Professor Jun-Ichi Hayashi from the University of Tsukuba in Japan, known as the white lion to his students given his white hair and powerful voice, challenges the current consensus surrounding the mitochondrial theory of aging, proposing epigenetic regulation, and not genetic mutation, may be responsible for the age-related effects seen in mitochondria. When Hayashi and colleagues tested their theory, they reversed the age defects in cell lines collected from 97-year-old Japanese participants. They then singled out two genes involved in glycine production which they believed are responsible for the mitochondria reversal. The findings thus suggest that a glycine supplementation could help curb aging or age-related diseases.

hourglass aging

Image: Huff Post

Mitochondria are popularly known as the “cell’s powerhouse”, since they’re responsible for producing energy through cellular respiration. One of the unique features of mitochondria is that they contain their own DNA – mitochondrial DNA (mtDNA). All the other DNA of a cell is found in the nucleus (nDNA). Most scientists claim that the mitochondria through mutations sustained in its DNA is involved in aging, since the mutations cause abnormal functions.

The mitochondrial theory of aging (MTA) was first proposed in 1972 by Denham Harman, the “father” of the free radical theory of aging (FRTA). Basically, as we age these mutations add up and the mitochondria is less efficient at producing energy, reducing lifespan and triggering aging-related characteristics such as weight and hair loss, curvature of the spine and osteoporosis. The brain is perhaps the most important organ affected by aging, since it consumes more energy than any other organ of the body. An energy deficit in the brain and central nervous system affects the activities of all organs throughout the body as well as mental acuity and mood.

Professor Hayashi. Credit: Image courtesy of University of Tsukuba

Professor Hayashi. Credit: Image courtesy of University of Tsukuba

Hayashi’s team, however, claims that the MTA has one severe flaw: it’s not DNA mutation, but epigenetic regulations that cause the mitochondrial defects. They collected  human fibroblast cell lines derived from young people (ranging in age from a fetus to a 12 year old) and elderly people (ranging in age from 80-97 years old). Then mitochondrial respiration and the amount of DNA damage in the mitochondria of the two groups was studied. Hayashi  expected to see reduced mitochondrial respiration and more DNA damage in the older cells, but while the elderly group indeed showed reduced respiration, there DNA differences between the two groups was minute. This is when they got the idea that epigenetics – environmental changes that alter the structure of DNA, without affecting its sequence – may have a part to play.

If they were right, then changing cells by genetically reprogramming them into an embryonic stem cell-like state would cancel any epigenetic effects. So, they put it to the test and the human fibroblast cell lines from both young and old participants were then converted into a stem-like state, then turned back into fibroblasts and their mitochondrial respiratory function examined. In an amazing twist of events, all of the resulting mitochondria had respiration rates comparable to those of the fetal fibroblast cell line, irrespective of whether they were derived from young or elderly people. This provides significant evidence to back their claim that mitochondria anomalies, and subsequently human cell aging, are governed by epigenetics.

They then identified two genes that might be controlled epigenetically and cause the age-related defects. The genes, CGAT and SHMT2, regulate glycine production in mitochondria. Glycine is the smallest of the amino acids. It is ambivalent, meaning that it can be inside or outside of the protein molecule.

Moreover, by changing the expression of these two genes, the team showed they could induce defects or restore mitochondrial function in the fibroblast cell lines. For instance, adding glycine for 10 days to the culture medium of the 97 year old fibroblast cell line restored its respiratory function, as reported in Scientific Reports. But could it work for other types of cells? If so, then human aging could be slowed down or even hampered using something like glycen supplements. Of course, this is but a part of the aging puzzle. There are also other things we need to worry about like telomerase length, stem cell death, cancer, transcription error to name but a few.

Scientists find gene that plays a key role in aging

At a rather strange location for a medical announcement, the Bellagio Hotel in Las Vegas, Dr. Florence Comite faced some of the best researchers in the field of aging. They gathered there for the 17th annual Age Management Medicine Group conference, and Dr. Comite had an exciting announcement to make: researchers have found a crucial gene responsible for aging.

Genetics may hold the key to very long lives. Image credits: Telegraph.

The head of that team is Dr. Stephen Coles, a UCLA gerontologist has dedicated his life to studying supercentenarians – people who live to be 110 and older. He wanted to see what these people have in common, what makes them so special, and if this could be applied to other people.

“When we interviewed these people we found they had very little in common,” said Coles, a few days before the announcement. “Some of them drink Jim Beam alcohol every day and some are tea-totallers. Some, surprisingly, smoke cigarettes, some have never smoked a day in their life. And some drink and smoke heavily, their lifestyles are terrible. But one thing they all have in common is longevity runs in the family.”

This seems to indicate that it isn’t just lifestyle which makes a difference – genetics also plays a key role. This was good news for Coles and his team; it means that if they found the genes which are responsible for reaching great ages, they could figure out how this could be applied to others. Over the past year, Coles and his team, which includes researchers based at Stanford University, and also at institutions in New York City, Boston and Italy, did full genome sequencing on 23 supercentenarians. Using these results, they believe they figured out what separates the old people from the very old people – and this is a key difference.

In the US, there are over 55,000 people over 100 years old, but only 60 people over 110. Comite believes that one gene is responsible for this difference. The gene is found in all people, but it has a crucial variant which is responsible for increased life expectancy.

“My personal hypothesis for five years has been there is something that allows supercentenarians to go further,” said Coles, “but we have always been prepared to be disappointed.” Though there is nothing disappointing about his results, the finding is phenomenal, and has an army of pharmaceutical companies banging down his door.”

Naturally, there has been a great deal of interest from the private sector for this research, but Coles did his best to protect his research.

“Many drug companies are after me,” said Coles, “and I have been very secretive, because we have competitors on the east coast, and we don’t want them to have access to the gene too quickly, because then they will get it before us and scoop us.”

Dr. Florence Comite (pictured here) reported that Stephen Coles and his team believe have found a key gene related to aging, but they are secretive about their findings.

When asked why he was so secretive, Coles revealed a pessimistic, yet accurate view of the American medical system. Basically, people want to make money – and people working in big pharma companies even more so than others.

“You are touching on a very deep philosophical question about how our country works,” he said. “We are a capitalist society, and many drug companies might convert this new knowledge to something they can make money off of.”

His research is more valuable than money, he explains – it has the potential to do a great deal of good to humanity; this is not about selling “life extension”, but rather about understanding how aging works, and making things available for everybody.

“Our goal is not money, and it is not about doing some exclusive thing and sneakily selling our findings to a pharmaceutical company then backing out,” said Coles. “Our goal is doing the research for humanity and ideally having the discovery being available for anyone in the general public.”

While announced, the research hasn’t been published yet – it will be published on November 14, in the journal PLOS ONE. I’m pretty excited and can barely wait to read the actual research, but until I do, I’m also a bit skeptical. These are pretty bold claims the researchers are making – hopefully, they also have the science to back it up.

Edit: Corrected a factual error. Florence Comite was not involved in the study, she was just announcing the discovery at a conference where Dr. Coles couldn’t attend.

Aging successfully reversed in mice – human trials to start next

As incredible as it may sound, scientists have successfully reversed the aging process in mice, according to a new study published in Cell.

Reversing aging, a real possibility?

Many of the chronic diseases that exist in older adults constitute a highly significant social and economic burden to the community; if you think about it, eliminating (or at least alleviating) the effects of aging means not only increasing the lifespan, but also increasing the life quality and reducing health costs… it could pave the way for a new world. But can this really be done, or is it merely wishful thinking?

Lead researcher David Sinclair of the University of New South Wales and his team showed that at least in mice, it’s not only possible – it’s already been done. After administering a certain compound to the mice, muscle degeneration and diseases caused by aging were reversed, with surprisingly successful results:

“I’ve been studying aging at the molecular level now for nearly 20 years and I didn’t think I’d see a day when ageing could be reversed. I thought we’d be lucky to slow it down a little bit. The mice had more energy, their muscles were as though they’d be exercising and it was able to mimic the benefits of diet and exercise just within a week. We think that should be able to keep people healthier for longer and keep them from getting diseases of ageing.”, Sinclair said.

sirtuin

The compound in case is Sirtuin 1 (SIRT1), one of seven mammalian sirtuins, known for playing an important role in metabolic homeostasis (the process of regulating and stabilizing metabolism). Generally speaking, sirtuins are a class of proteins which regulate many important biological pathways – they have been linked to longevity before. The trick here was to stimulate communication between the mitochondria and the cell nucleus, with the compound the increasing the level of a naturally occurring substance in the human body called nicotinamide adenine dinucleotide. This substance decreases as people age, though not as much in people who exercise and follow a healthy diet.

The compound that the mice ate had fast, remarkable results; their muscles became toned, as if they’d been exercising. Inflammation, a key factor in many disease processes, was drastically reduced. Insulin resistance also declined dramatically and the mice had much more energy overall. The process was absolutely amazing – scientists compared it to a 60 year old having the muscle fitness and overall stamina of a 20 year old. But to make this even more amazing – it all took just one week! It almost sounds too good to be true, which brings us to the next issue…

Why isn’t this the biggest news?

David Sinclair.

The thing is, this research was funded before… sort of. Sirtris, a company developed by Sinclair was owned by GlaxoSmithKline, and human trials were set to start for this very treatment. However, a big research team from the Institute of Healthy Ageing at the University College of London published an article in Nature saying that the underlying mechanism was bogus, and that Sinclair’s initial results were simply experimental flaw. The study received good reviews, and was generally approved by the scientific community. All funding was pulled, and the project was killed, leaving Sinclair discredited.

But he pulled on! He kept going, and with this study, he proves that the underlying mechanism was right all along. It is a sad story of science doing the right thing and double checking, which only resulted in delaying something which seems to be a monumental discovery. But even now, investors are likely hesitant to invest in his project.

Even as aging was successfully reversed in mice, Sinclair says he needs to raise more money before he can commit to a date when trials may begin in humans. Hopefully, his efforts won’t be in vain.

Scientific Reference: http://dx.doi.org/10.1016/j.celrep.2014.01.031
2014 Sinclair at TEDX Sydney