Tag Archives: lifespan

Scientists increase worm’s lifespan by 500%

C. elegans, a nematode worm, is one of the most widely used model organisms in labs across the world. It’s often the animal of choice when studying longevity because of its relatively short lifespan of only three to four weeks, which allows scientists to quickly discern the effects of genetics and the environment. Now, an international team of researchers claims they have tweaked the worm’s genes, extending its lifespan by up to 500%.

Photograph of the Caenorhabditis elegans adult hermaphrodite . Scale bar, 100 μm.  Credit: ResearchGate, Nobuyuki Hamada.

The team, which includes scientists affiliated with the Buck Institute for Research on Aging in Novato, Calif., and Nanjing University in China, focused on two major pathways: the insulin signaling (IIS) and TOR pathways. These pathways are “conserved”, meaning they’ve been passed down by a common ancestor to both worms and humans.

Researchers mutated both pathways, expecting a 100% increase in lifespan due to the mutated ISS pathways and a 30% increase from the TOR pathway. Instead, they noticed that their altered worms lived up to 500% longer (4-5 months versus 3-4 weeks) than they normally would.

Jarod A. Rollins of the MDI Biological Laboratory in Bar Harbor, Maine. Credit: MDI Biological Laboratory.

“The synergistic extension is really wild,” said Jared Rollins of Nanjing University, who is one of the lead authors of the new study, which was published in Cell Reports. “The effect isn’t one plus one equals two, it’s one plus one equals five. Our findings demonstrate that nothing in nature exists in a vacuum; in order to develop the most effective anti-aging treatments we have to look at longevity networks rather than individual pathways.”

This synergistic interaction could pave the way for novel therapies designed to extend the human lifespan similarly to how some combination therapies treat cancer presently.

“Despite the discovery in C. elegans of cellular pathways that govern aging, it hasn’t been clear how these pathways interact,” said Hermann Haller, M.D., president of the Mount Desert Island Biological Laboratory. “By helping to characterize these interactions, our scientists are paving the way for much-needed therapies to increase healthy lifespan for a rapidly aging population.”

These findings may also explain why scientists have been unable to put their finger on a single gene, or even a collection of genes, that allows some people to reach extraordinary old ages free of major illnesses.

In the future, Rollins and colleagues want to focus their research on how longevity is regulated by mitochondria, the organelles responsible for supplying cells with energy. Previously, studies have suggested that poor mitochondria function is associated with aging.

DNA reveals lifespan of mammoth and other extinct animals

During the last ice age — some 100,000 to 15,000 years ago — mammoths were widespread in the northern hemisphere from Spain to Alaska. Although some endured on a tiny island in the Arctic until 1650 BCE, most mammoths perished about 10,000 years ago during a time when they still interacted with humans. A new study that estimated a species’ lifespan from DNA suggests that these mammoths were most likely much older than the human hunters on their prowl, reaching up to 60 years of age.

Credit: Wikimedia Commons.

The team of researchers at CSIRO and the University of Western Australia estimated a species’ lifespan based on its genome sequence. In order to unravel the lifespan clock, the researchers screened 42 genes from the DNA of 252 vertebrate species, both living and extinct. The higher the density of these genes, the higher the predicted lifespan.

When studying extinct animals, the researchers had to also use their living relatives and descendants for reference. In the case of the wooly mammoth and straight-tusked elephant, the Australian researchers performed estimations based on the genome of the modern African elephant, whose lifespan is of about 65 years.

So how long did mammoths live? The researchers estimate that they were able to live up to 60, and the same applied for straight-tusked elephants. Meanwhile, the maximum lifespan of Homo sapiens was deemed to be 38 years, according to this method. This may seem to invalidate the method seeing how the average lifespan in the United States currently is 78, but this figure actually matches other estimates of early modern human lifespans before the advent of medicine, agriculture, and sanitation.

Neanderthals and Denisovans, our close extinct relatives from the genus Homo, had a maximum lifespan of 37.8, very similar to modern humans living around the same time.

“We estimated that Denisovans and Neanderthals both had a lifespan of 37.8 years. This suggests that these extinct Hominidae species had similar lifespans to their early human… counterparts,” the researchers wrote.

The famous Lonesome George was the last remaining Pinta tortoise (C. abingdoni) when he died in 2012. He had been living in captivity at the Charles Darwin Research Station on the Galapagos Islands since 1972 and died at age 100. That’s relatively close to the maximum lifespan estimate of 120 years found by the study.

Other extinct animals whose lifespan were calculated by the study include the little bush moa (23 years) and the passenger pigeon (28 years). The animal with the largest lifespan is the bowhead whale (268 years). However, the longest-living vertebrate may be the Greenland shark, which could live to see 512 years of age, according to a 2017 study.

The estimates for invertebrates weren’t nearly as accurate, possibly because they do not exhibit the targetted genes to the same extent as vertebrates.

In the future, these genes could be used to further studying aging. For instance, there’s a debate among researchers as to what is the absolute limit of human longevity. The method elaborated by this study, however, cannot be used on individuals.

“It cannot be used to determine the lifespan of any individual human and the purpose of this study was to determine an important parameter of ecological significance which may assist in wildlife management,” said Benjamin Mayne, a scientist at the Commonwealth Scientific and Industrial Research Organisation (CSIRO) in Western Australia.

The findings appeared in the journal Scientific Reports.

Yalenusresea

Drug cocktails can almost double lifespan — in worms and fruit flies, so far

A cocktail of drugs has been shown to effectively double lifespan — but so far, it only works for flies and worms.

Yalenusresea

Microscope image of Caenorhabditis elegans worms used in the study.
Image credits Jan Gruber.

One research team from Singapore wants to extend human lifespan through pharmacological means. It’s a lofty goal, but the results are already coming in. In a new study, the team reports they’ve successfully increased the healthy lifespan and delayed the rate of aging in a tiny little worm known as Caenorhabditis elegans. The study is the product of a collaboration between the Yale-NUS College, and the National University of Singapore (NUS).

Longer life for simple life

“Many countries in the world, including Singapore, are facing problems related to ageing populations,” said Dr. Gruber, an Assistant Professor of Biochemistry at Yale-NUS College, who lead the research effort.

“If we can find a way to extend healthy lifespan and delay ageing in people, we can counteract the detrimental effects of an ageing population, providing countries not only medical and economic benefits, but also a better quality of life for their people.”

Some widely-employed drugs have quite interesting effects beyond their primary indented use. For example, rapamycin/sirolimus, a drug administered following organ transplants to prevent organ rejection, has been shown to increase the lifespan of several simple (non-human) species. Gruber’s team wanted to see whether cocktails of such life-prolonging drugs could be more efficient at staving off old age than the sum of their individual components. They tested combinations of two or three compounds at a time. Drugs in each mix were selected to target a different metabolic pathway related to aging in C. elegans, a free-living roundworm that grows to around 1 mm (0.03 in) in length.

The first good sign is that the drugs didn’t have any negative impact on the worms’ health. The second good sign was that the cocktails were much more efficient than the individual compounds. For example, three-drug cocktails almost doubled the average lifespan of the worms. Needless to say, this is quite the achievement — no other drug intervention has ever had such an effect on lifespan in adult animals, the team reports.

The third and arguably most exciting finding is that treated worms were healthier and spent a larger part of their life in good health across all ages. So not only did they live more, but they lived better for a greater part of their lives compared to untreated worms. In collaboration with Associate Professor Nicholas Tolwinski (also at the Yale-NUS), the researchers found that the common fruit flies (Drosophila melanogaster) treated with the drug cocktails also had significantly increased lifespans.

The fact that the drugs worked in two organisms with distinct evolutionary backgrounds suggests that they work on ancient aging-related pathways. It’s likely, then, that they would work similarly in humans.

“We would benefit not only from having longer lives, but also spend more of those years free from age-related diseases like arthritis, cardiovascular disease, cancer, or Alzheimer’s disease,” Dr. Gruber said. “These diseases currently require very expensive treatments, so the economic benefits of being healthier for longer would be enormous.”

Dr. Gruber says that the research is just a proof-of-principle. It’s meant to show that the approach is viable, that a multiple-drug approach could be used to extend the healthy lifespan of adult animals — perhaps even humans.

In the future, the team plans to extend their research to cover three key areas. First, they want to develop drugs and drug mixes that are even more effective than the ones used in this study. They also want to determine exactly how each compound works to delay aging, in a bid to create computer models that can test quickly test many more potential drug combinations. Ultimately, they want to try and apply the findings in slowing down aging for humans.

The paper “Drug Synergy Slows Aging and Improves Healthspan through IGF and SREBP Lipid Signaling” has been published in the journal Developmental Cell.

Credit: Arne Hendriks, Flickr.

We’re still far away from finding a limit to human lifespan

Credit: Arne Hendriks, Flickr.

Pictured here is Jeanne Calment, who lived to be 122. She’s officially the oldest human being that we know of. Credit: Arne Hendriks, Flickr.

If there’s a biological limit to how long humans can live, we haven’t reached it yet. This is the conclusion of a recent study of people aged over 105, finding that their risk of death slows and even plateaus past this age. According to the study, if individuals can live past very perilous ages (their 70s, 80s, and 90s), they can hope to live well into their 110s.

The oldest human being ever hasn’t been born yet

The longest a human has ever lived — that we know of — is 122, a record set by a Frenchwoman called Jeanne Calment. She died 21 years ago, and no one has grown older since.

In 2016, a study performed by researchers at the Albert Einstein College of Medicine in the Bronx analyzed data from the Human Mortality Database, which included data such as when these individuals became deceased, from over 40 countries. The researchers found that since 1900, the survival rate of people 70 years and older had steadily increased with their year of birth. However, this didn’t occur for people aged 100 years and older, suggesting a possible limit to lifespan. Specifically, the authors argued that the biological limit of human beings is 115, simply making Calment an outlier.

This study started a lively debate among scholars, many arguing that the conclusions were based on flawed statistical methods. Although, to be fair, any study attempting to assess the limits of human longevity is challenging by virtue of the nature of its object of inquiry. First of all, there aren’t that many people who are 100 or older, which makes conclusions difficult to draw given the sample size. Secondly, people born in 1900 or around the time often can’t definitely prove their date of birth, as not all countries accurately recorded information about their citizens at the time.

“The statistics aren’t good enough to be able to say you can’t live much longer than that, based on the data we have,” said report author Siegfried Hekimi, chairman of developmental biology at McGill University in Montreal. “It’s simply not good enough to make that claim.”

Kenneth Wachter, a professor of demography and statistics at the University of California, Berkeley, and colleagues came to a totally different conclusion from the 2016 study. They tracked the death trajectories of nearly 4,000 Italian residents who reached age 105 between 2009 and 2015.  Over 87% of these people were women and during the time period, 2,880 deaths had occurred.

The researchers found that the odds of survival decline rapidly as a person enters middle and old age. For instance, Italian women who reached 90 had a 15% chance of dying within the year and could expect to live another six years, on average. If they made it 95, however, the odds of dying within the year increased to 24% and life expectancy dropped to 3.7 years.

This would logically suggest that for every aged year, the odds of dying within the year increase more and more. But that’s not what happened — once they hit 105, the chance of surviving hit a plateau of 50% each year, the researchers reported in the journal Science.

“If mortality rates kept rising at the rates they rise from age 40 to age 90, then there would be a strong barrier to progress at extreme ages—great diminishing returns to behavioral change or to new medical advances,” Wachter said. “The fact these rates ultimately level out gives hope there’s more leeway for those advances.”

“The risk of death is very high at 105 years, but next year it’s not higher,” Hekimi commented about the new study. “Every year you have the same chance of dying, and every year you can be the one who wins the coin toss.”

Wachter says that the plateau is likely due to the influence of genes but also healthy life choices. However, there is no clear-cut genetics that enable people to reach ripe old ages. For instance, genes that seem to be supporting extended lifespan on Okinawa are not the same as ones found in England.

“When you look at a group of older people who are all the same age, some are already quite frail and some are robust. There’s a big difference in the level of frailty,” Wachter said.

“People who go to college 50th reunions, you just look around you and some people are climbing mountains while some people are walking with canes. Now go 15 to 20 years later, the people who were already frail are the ones who are likely to have died,” he said.

The present study suggests that it is possible to extend the survival plateau earlier into the average human lifespan, thus making it likelier for more people to survive into their 100s. Imagine that those people who are 115 today were born in a time when they didn’t have access to modern healthcare and nutritional information. It’s extremely likely that the people who will eventually reach the peak of human lifespan haven’t’ been born yet.

“It gives us a good piece of hope, because there is now lots of opportunity to look at these bad variants as they are in populations today and to try to understand the interaction of those genetic variants with potential medicines and different health challenges,” Wachter said.

“This basic theory could help us inform medical progress and public health progress 10 to 15 years from now as genetic research continues,” he said.

Credit: Wikimedia Commons.

Being too social can shorten your lifespan — if you’re a marmot

Credit: Wikimedia Commons.

Credit: Wikimedia Commons.

Having a rich social life has been frequently correlated with longevity. Humans are so dependent on other people that, in the past, being excluded from the tribe was basically the equivalent of receiving a death sentence. Other studies have found a similar social-longevity link in all studied non-human social species  — all but one adorable rodent: the marmot.

For the largest squirrel hanging around with its peers for too long can lead to premature death. That’s the conclusion a team of biologists at UCLA led by Daniel Blumstein came to after studying 66 female yellow-bellied marmots (Marmota flaviventer) between 2002 and 2015.

Blumstein and colleagues tracked the activities of various marmot groups, carefully noting and measuring their interactions such as burrow sharing and grooming. The researchers expected to encounter a positive correlation between close social contact and longevity but it was quickly evident the reverse held true.

“These results are inconsistent with what has been previously reported in humans and other species,” the authors reported in the journal Proceedings of the Royal Society B.

The more social the marmot was, the shorter their lifespan, the scientists found. Conversely, these large ground squirrels live longer, on average, if they were less social.

But these findings weren’t entirely surprising. Previously, another study found female marmots connected to large social networks were more likely to die over the winter than those with few or no social relationships.

“More social marmots are less likely to survive over the winter, and they live shorter lives, on average,” said Blumstein, who is a UCLA professor of ecology and evolutionary biology. “We’re finding costs for adult female marmots to be nice to other female marmots. This species of marmots is not highly social, and for them, it seems costly to interact with others.”

Marmots are, according to Blumstein, so-called “facultatively social” animals, meaning you can encounter them in various social configurations such as large groups, small family-based mobs, pairs, and in complete isolation.

A 2010 article in the journal PLOS which summarized 148 studies of the effects of social isolation on human mortality found that lack of social contact dramatically raises the risk of dying an early death in humans. People without friends have a staggering 50% higher mortality rate than people with strong social networks.

Our relationships can influence our health in a variety of ways, researchers say. One important aspect is dealing with stress, for instance. Having people who care and support you can help a great deal when facing stressful situations. Friends and family are known to encourage healthy behavior such as eating better, exercising, getting more sleep and visiting the doctor.  Social relationships also provide meaning to our lives and might influence us to take better care of ourselves or take fewer risks.

For the yellow-bellied marmot, at least, having other furry friends around offers no protection against stress. Perhaps these social interactions themselves are stressful. Blumstein speculates that their results might be because marmots aren’t necessarily social; being social is an option rather than a necessity for them. As such, the energy spent on ‘being social’ might shorten their lives.  

“Being social has benefits, but we’re finding costs of being too social. By studying a species that doesn’t want to be social, we are finding insights we wouldn’t have found by studying social primates,” Blumstein said.

Scientific reference: Strong social relationships are associated with decreased longevity in a facultatively social mammal, Proceedings of the Royal Society Brspb.royalsocietypublishing.or … .1098/rspb.2017.1934 .