Tag Archives: longevity

flatworm

Scientists prove ‘immortal worms’ can regenerate indefinitely and stay forever young

flatworm

University of Nottingham scientists spurred a slew of debate in 2008 when they claimed their object of study, the planaria or “flatworm”, might actually be immortal, possessing an indefinite ability to regenerate its cells and thus practically never grow old. In fact, an important distinction must be made, it’s not that the flatworm never grows old that’s interesting, it’s the fact that it stays forever young!

As you can imagine a discovery of such interest didn’t go unnoticed, and it wasn’t long before the essential question was put – how do you really know that they’re immortal? A simple question, with an extremely complicated answer. To answer this question, you must first define what makes an animal immortal in the first place. Simply standing by an allegedly immortal animal waiting for it to die is far from being practical at all, in scientific terms. The researchers identified a number of genetic criteria which need to be filled in order for an animal to be considered immortal. First of all, it needs to retain the ability of replacing old cells with new cells indefinitely, and this is what stem cells are for.

Most animal in the world gradually tend to lose this ability as they age, thus causing them to get older, function improperly and eventually die. The flatworm not only is able to regenerate its old, dead cells, but it can literary grow a new brain, gut or tail when severed in two. Both cut ends grow into a new individual. Over the course of their several year long research, Notthingham University scientists have cloned a few thousand individuals starting from one single flatworm that was cut in two, which were also at their own term cut in two, and so on so forth. Biologist Dr. Aziz Aboobaker, who heads the project explains:

“We’ve been studying two types of planarian worms; those that reproduce sexually, like us, and those that reproduce asexually, simply dividing in two,” said Dr. Aziz Aboobaker from the University’s School of Biology.

“Both appear to regenerate indefinitely by growing new muscles, skin, guts and even entire brains over and over again.

“Usually when stem cells divide — to heal wounds, or during reproduction or for growth — they start to show signs of aging. This means that the stem cells are no longer able to divide and so become less able to replace exhausted specialized cells in the tissues of our bodies.

“Our aging skin is perhaps the most visible example of this effect. Planarian worms and their stem cells are somehow able to avoid the aging process and to keep their cells dividing.”

The key lies in DNA

Each time a cell divides, the tip of its DNA, called the telomere, gets shorter. An enzyme called telomerase regenerates the telomores, however in most sexually reproductive organisms it is only active during the organism’s development. Once it reaches maturity, the enzyme stops functioning, and the telomeres become shorter and shorter until cell replication is made impossible, otherwise the DNA would become too severely damaged. An immortal animal is able to maintain telomere length indefinitely so that they can continue to replicate, and Dr. Aboobaker and colleagues were able to demonstrate that the flatworms actively maintain the ends of their chromosomes in adult stem cells, leading to theoretical immortality.

Doctoral student Thomas Tan performed a series of crucial experiments, as part of the project, in order to scientifically explain the worm’s fascinating, yet theoretical, immortality. A possible planarian version of the gene coding for the telomerase enzyme was identified, and had its activity turned off. Since the telomere shrank in size, it was thus confirmed to be the right gene. Armed with this new found knowledge, the scientists monitored and measured the gene and observed that asexual worms dramatically increase the activity of this gene when they regenerate, allowing stem cells to maintain their telomeres as they divide to replace missing tissues.

“It was serendipitous to be sandwiched between Professor Edward Louis’s yeast genetics lab and the Children’s Brain Tumour Research Centre, both University of Nottingham research centres with expertise in telomere biology. Aziz and Ed kept demanding clearer proof and I feel we have been able to give a very satisfying answer,” Dr. Tan stated.

From immortal worms to immortal humans

The same didn’t apply to sexual flatworms, though, which still, however, display the same apparently indefinite ability to regenerate. The researchers explain that either these flatworms will eventually shorten their telomeres, albeit very gradually, or they found a different way to maintain indefinite cell replication that doesn’t involve the telomerase  enzyme.

The researchers claim that the next natural step is to study how this might apply to more complex organisms, like humans.

“The next goals for us are to understand the mechanisms in more detail and to understand more about how you evolve an immortal animal,” said Aboobaker.

“The worms are a model system in which we can ask questions, like is it possible for a multicellular animals to be immortal and avoid the effects of aging?”

“If so, how does this animal do this in comparison to animals that don’t? Of course we hope that this impacts humans, that’s why we do it. But we aren’t planning on making any drugs or medicines… other people are, I’m sure.”

The findings were published in the journal PNAS. University of Nottingham PR

mice longevity gene

Sirtuin back in the highlight as longevity gene – overexpression prelongs male mice lifespan by 15%

For a number of years now researchers have been studying the sirtuin gene and the proteins encoded in it as it is believed to be directly linked to prolonged lifespan. A myriad of individual studies were performed with mixed results, and so far hundreds of millions have been allocated for research in this direction. A certain company has actually leaped ahead and advertised cosmetic products on the market which allegedly stimulate an enhanced expression of the gene, despite the scientific community hasn’t generally concluded that sirtuin may lead to a prolonged life.

It all began when a link between the sirtuin gene in yeast and maximum lifespan was observed, and since then scientists all over the world have been paying very close attention to it. To try to see if it might impact human lifespan as well, scientists have almost universally direct their attention towards SIRT1, another member of the sirtuin gene family, which is expressed in mammals and most closely related to the yeast longevity gene. Biotech companies have invested a lot of money in sirtuin research, with many boosting impressive results. Most recently, however, scientists have begun to question its longevity link. With this in mind, a group of researchers demonstrated that sirtuin has no particular connection to enhanced lifespan fruit flies or nematodes, as previously reported on ZME Science. Moreover, absolutely no effect of SIRT1 on longevity in mammals has been reported as of yet, although it’s been associated with a healthier metabolism in mice fed a high-fat die, and thus longer life.

Looking elsewhere in the sirtuin family

mice longevity gene Another member of the sirtuin gene family, SIRT6, looks a lot more interesting, however. While all efforts are concentrated on SIRT1, molecular biologist Haim Cohen of Bar-Ilan University in Ramat-Gan, Israel chose to have a different look towards a much more obscure route. “People were mostly interested in SIRT1,” he says. “So I thought it might be better for us as a new lab to work on something that is less crowded.”

Cohen’s research and interest proved to pay off, eventually. A previous research from 2006 observed how mice lacking SIRT6 were sickly, small, and with a reduced ability of repairing damaged DNA – these mice died within a month. Cohen wanted to see what would happen if the opposite were to occur, and had a strain of mice express higher levels of SIRT6 than normal. What he found was that male mice median lifespan  rose by 14.5% in one line of their transgenic mice and 9.9% in another. When maximum life span is concerned, the metric rose by 15.8% in the first line of mice, and 13.1% in the second. Curiously enough, there weren’t any signaled differences in lifespan for female mice.

The missing genetic link to longevity? Not so fast…

“It’s a good bet that each of the sirtuins does something interesting,” says Richard Miller, who studies ageing at the University of Michigan in Ann Arbor. “But the case for whether any one of them is important to ageing and longevity in mammals is somewhat weak and circumstantial.”

Miller makes reference to the fact that the particular strain of mice used in the research is prone to a cancerous tumor, most evident in males. It’s possible that SIRT6 might have an anti-cancer effect. What about the clear difference between the female and male mice? Female mice were found to live in the strain were found live 15% more than male, prior to SIRT6 treatment. Cohen speculates that the male mice inflicted with the hyperactive gene caught up with the female mice, as SIRT6 is mimicking effects already seen in the females.

Also it’s important to note whether SIRT6 addresses any improvements in clear aging conditions, like cataract formation and declines in memory and mobility, even cell degradation. It might just improve the metabolism. The fact remains, however, that the study, still in its infancy, is of extreme interest, and prove to an extent that all this focus may not have been in vain after all. There other genes in the sirtuin family which haven’t been granted the necessary attention, and those as well might show some promising results.

“People are just beginning to come to grips with the fact that there are seven sirtuins and each may do different things,” says Miller. “The quicker people stop thinking in terms of ‘it’s either gold or tin’ and start addressing the nuances of sirtuin function, the better.”

The results were published in the journal Nature.

Illustration credit

‘Longevity gene’ debunked – there’s no such thing

Scientists from the UK and Hungary have run various experiments to verify the claim of US researchers that a certain gene is responsible for the increase of lifespan, as shown in some test organisms. Their results show, in fact, that the so called “longevity gene” allegedly responsible for the generation of an anti-aging protein doesn’t affect longevity at all.

The round­worm C. ele­gans, used in some ag­ing studies. (c) Wikimedia Commons, National Human Genome Research Institut

The round­worm C. ele­gans, used in some ag­ing studies. (c) Wikimedia Commons, National Human Genome Research Institut

The substance controlled by the gene, called sirtuin, has since been the subject of heavy marketing campaigns by cosmetic companies who advertised sirtuin enhancing anti-aging products, like anti-wrinkle creams or anti-aging pills.

The initial research which came with the longevity gene conclusion based their work on the study of yeast, nem­a­tode worms and fruit flies, of­ten used as mod­els for the bi­ol­o­gy of hu­man aging. Their initial conclusion was that when the or­gan­is­ms over­pro­duced sir­tuin, they lived long­er, by as much as 50 per­cent in the case of nem­a­todes. Another connection to increased lifespan was found to be dietary restrictions, which scientists claimed stimulated the production of sirtuins.

A subsequent research, however, published in this week’s edition of the jour­nal Na­ture, led by Da­vid Gems and col­leagues at Uni­vers­ity Col­lege Lon­don, shows that there isn’t any conclusive evidence that links sirtuin to enhanced lifespan.

“These re­sults are very sur­pris­ing. We have re-ex­am­ined the key ex­pe­ri­ments link­ing sir­tuin with longe­vity in an­i­mals and none seem to stand up to close scru­ti­ny. Sir­tu­ins, far from be­ing a key to longe­vity, ap­pear to have noth­ing to do with ex­tending life,” Gems said. “But I think this is good news in a way: af­ter all, re­vis­ing old ideas can be as im­por­tant as pre­sent­ing new ones to as­sure sci­en­tif­ic prog­ress. This work should help to re­di­rect sci­en­tif­ic ef­forts to­ward those pro­cesses that really do con­trol age­ing.”

Re­search­ers at the Uni­vers­ity of Wash­ing­ton, Se­at­tle, and Sem­mel­weis Uni­vers­ity, Bu­da­pest, ex­am­ined two strains of nem­a­tode worm, each from a dif­fer­ent pri­or stu­dy. These were ma­ni­pu­lated to have a hy­per­ac­tive sir­tuin gene to that the hypothesis might be tested. The nematode indeed was initially found to live longer, but subsequent tests showed that after living conditions were made the same for both normal and genetically-enhanced worms, that there wasn’t any considerable difference in lifespan which could’ve been attributed to sirtuin. Suspecting that some other genetic factor must have caused the longevity, they identified a mutation in a gene involved in the development of nerve cells as the cause.

In the case of the fruit-fly, were considerable longevity was also reported, scientists actually engineered a new strain of fruit fly, Dro­soph­i­la melanogaster, which could hyper-actively generate sirtuin. They found no reason to consider the new strain particularly long-lived.

Finally, the dietary restriction was also put to the test. ak­ing mu­tant fruit flies that lacked the sir­tuin gene, the re­search­ers showed that di­e­tary re­stric­tion still in­creased life­span. So di­e­tary re­stric­tion was work­ing in­de­pend­ently of sir­tu­ins.

All those sirtuin-based creams and pills are nothing but expensive placebos.

114 year old Walter Breuning, the oldest attest individual to have lived. Breuning died Thursday, April 14, 2011 of natural causes in a Great Falls hospital.

The secret to a long life: consciousness

114 year old Walter Breuning, the oldest attest individual to have lived. Breuning died Thursday, April 14, 2011 of natural causes in a Great Falls hospital.

114 year old Walter Breuning, the oldest attestest individual to have lived. Breuning died Thursday, April 14, 2011 of natural causes in a Great Falls hospital.

A healthy life style, plenty of exercise and good genes might be your best bet, if you’re looking for a long life, but an eight decade study in the making found one common denominator – the answer to longevity is consciousness.

In 1921, in a quest to understand what really sets apart people who happen to reach 80, even 90 years old, Dr. Terman embarked patiently in a life long study. He chose 1,528 bright San Francisco 11-year-olds, and followed each individual with respect to their personality, parents marriages, play habits and so on, with an interview being conducted every 5 or 10 years. Dr. Terman eventually died in 1956, but his colleagues continued the regular interviews with the original subjects, asking the same questions Dr. Terman had asked.

In 1990, Dr. Friedman and Leslie Martin, still a graduate student at the time, wanted to a dwell into a similar study, only to rejoicefuly find that a similar attempt had been made many decades before. So, the two followed in Dr. Terman’s footsteps and continued his legacy. Dr. Friedman and Dr. Martin meticulously went through Dr. Terman’s records, dredged up death certificates and asked Dr. Terman’s questions of study participants’ survivors, while at the same they also conducted a group analysis of other similar studies, and collaborated with experts from many fields.

Key traits for a long life: prudence and persistence

As part of the eight decade long study, Friedman and Martin found that the key features of a long life are prudence and persistence.

“The findings clearly revealed that the best childhood personality predictor of longevity was conscientiousness,” they write, “the qualities of a prudent, persistent, well-organized person, like a scientist-professor — somewhat obsessive and not at all carefree.”

The continuation of the study wasn’t without predicaments either. One of the major issues they faced was how to pose the same questions Dr. Terman put more than 80 years ago, and still keep the study relevant and consistent. For example one of Dr. Terman’s original questions he asked parents sounded like “How likely are you to upbraid a workman?”. Not quite familiar in contemporary terms, but by employing a complicated linguistic measurement called factor analysis, Dr. Martin said, the researchers were able to come up with the 21st-century equivalent: “How do you deal with co-workers?”

According to Dr. Friedman, “genes constitute about one-third of the factors leading to long life.” This means if your grand daddy lived to be 90, that doesn’t mean you’ll be too. What does consciousness has to do with longevity, then?

Conscious people are safer, older

Researchers have a couples of explanations for this. The most obvious explanation is that conscientious people are more likely to live healthy lifestyles, not smoke or drink to excess, wear seat belts, follow doctors’ orders and take medication as prescribed – conscious people are very safe. Secondly, conscientious people tend to find themselves not only in healthier situations but also in healthier relationships: happier marriages, better friendships, healthier work situations. A happier man is more likely to live longer – this doesn’t necessarily mean that conscious people are happier, just that they’re more like to be happy.

The most fascinating and important explanation that links consciousness with longevity is that some people are simply biologically predisposed to be not only more conscientiousness but also healthier, researchers found. ”

“We thought it must be something biological,” Dr. Friedman said. “We ruled out every other factor.”[…] “Not only do they tend to avoid violent deaths and illnesses linked to smoking and drinking,” they write, “but conscientious individuals are less prone to a whole host of diseases, not just those caused by dangerous habits.”

Stress is good for longevity

If you’ve been walking all your life on sunshine, don’t expect a few more years scrapped from the calendar.

“If you’re cheerful, very optimistic, especially in the face of illness and recovery, if you don’t consider the possibility that you might have setbacks, then those setbacks are harder to deal with,” Dr. Martin said. “If you’re one of those people who thinks everything’s fine — ‘no need to back up those computer files’ — the stress of failure, because you haven’t been more careful, is harmful. You almost set yourself up for more problems.”

A stress free lifestyle isn’t too helpful either, instead challenges that push you and make you more conscious of yourself and your surroundings have a much greater effect.

“There’s a misconception about stress,” Dr. Friedman said. “People think everyone should take it easy.” Rather, he said, “a hard job that is also stressful can be associated with longevity. Challenges, even if stressful, are also a link.” In the end, he said, “if people were involved, working hard, succeeded, were responsible —no matter what field they were in — they were more likely to live longer.”

Many people, of course, have to stay in a job they don’t like or don’t do well in. That’s bad stress, and they found those people were more likely to die young.

Other lifespan-increasing factors were having a very close social network, being extroverted, being aware of satisfaction with life as a whole, and being religious or spiritual. When it comes to the subject of married, researchers found that it was not influential factor in living longer, although having a healthy and loving marriage did play a big part – for men only that is. This might light some sparks, I’m sure.

If you’d like to find out more on the subject, the whole study has been carefully written for the general public in the form of a recently released book, titled “The Longevity Project: Surprising Discoveries for Health and Long Life from the Landmark Eight-Decade Study.”