It is the Holy Grail of health research, discovering the key to help people live longer.
Now scientists believe they may be one step closer.
A team at Yale School of Medicine have identified a hormone, produced by the thymus glad, extends lifespan by 40 per cent.
Their findings reveal increased levels of the hormone, known as FGF21, protects the immune system against the ravages of age.
Thanks for the link "Dio" I had not heard of it. At least one caveat however the 40% life extension believed to be caused by the "FGF21" applies only to mice as far as the researchers seem to be saying; no data on use in people. Probably be years before anyone would have any data on use in people. Deprenyl (along with metformin & rapamycin) on the other hand has decades of experience being prescribed/used by humans. From my 2nd link:Diogenes wrote:Have scientists discovered the elixir of youth? Hormone 'extends lifespan by 40%, protecting the immune system against the ravages of age'
Deprenyl is not only available by prescription but can also be obtained on line. It has been prescribed apparently for older dogs to help them with cognitive function. I have never tried it myself wonder if anyone else here has?Parkinson’s patients who take Selegiline live longer than matched patients who take only the other standard treatment (L-Dopa).
With a bit of clever genetic engineering, a team of scientists has just found an astonishing way to significantly expand the natural lifespan of mice. Now, at least one biotech company hopes to translate this breakthrough to fight aging in humans.
In a study published today in the journal Nature, medical researchers at Mayo Clinic College of Medicine—led by cell biologists Darren Baker and Jan van Deursen—have made this decade's biggest breakthrough in understanding the complex world of physical aging. The researchers found that systematically removing a category of living, stagnant cells (ones which can no longer reproduce) extends the lives of otherwise normal mice by 25 percent. Better yet, scouring these cells actually pushed back the process of aging, slowing the onset of various age-related illnesses like cataracts, heart and kidney deterioration, and even tumor formation.
"It's not just that we're making these mice live longer; they're actually stay healthier longer too. That's important, because if you were going to equate this to people, well, you don't want to just extend the years of life that people are miserable or hospitalized," says Baker.
The cells the scientists eliminated are called senescent cells. A senescent cell is an otherwise normal cell—say a skin or heart muscle cell—that has stopped dividing and reproducing. Right now, they're found all over your body. Now, these cells have long been known to be associated with aging, "for example, in mice or people or monkeys, you find an accumulations of these senescent cells over time and with age. And at sites of age-related disease, like osteoporosis, you'll also find these cells," says Baker. One theory behind why these cells exist in the first place is that hyper-stressed cells become senescent to prevent potentially cancerous, unfettered reproduction.
But until now, exactly what effect living senescent cells actually have on the body—either slowing aging, speeding it up, or not effecting the aging process at all—has largely been a mystery. But by leveraging modern techniques in genetic engineering, Baker and his colleagues finally set up an experiment that conclusively proved that the presence of senescent cells is largely a negative one. They shorten total lifespan and hasten the onset of age related illnesses, like cardiovascular disease.
Cellular Kill Switch
Although today's paper is the result of many careful experiments painstakingly developed over a 7 year period, "the beauty of this study is that it's actually really quite simple," says Baker. The scientists took advantage of the fact that one hallmark of senescent cells is that they steadily secrete a certain tumor-suppressing protein molecule called "p16Ink4a." We'll call it p16, and you can think of it as basically their calling card.
By rewriting a tiny portion of the mouse genetic code, Baker and van Deursen's team developed a genetic line of mice with cells that could, under the right circumstances, produce a powerful protein called caspase when they start secreting p16. Caspase acts essentially as a self-destruct button; when it's manufactured in a cell, that cell rapidly dies.
So what exactly are these circumstances where the p16 secreting cells start to create caspase and self-destruct? Well, only in the presence of a specific medicine the scientists could give the mice. With their highly-specific genetic tweak, the scientists had created a drug-initiated killswitch for senescent cells.
In today's paper, Baker and van Deursen's team reported what happened when the researchers turned on that killswitch in middle-aged mice, effectively scrubbing clean the mice of senescent cells. The medicine was injected into the genetically engineered mice's bellies when they were 12 months old. (Keep in mind, the process isn't perfect. Some senescent cells, including those found in the colon and liver managed to survive—possibly by avoiding the killswitch drug.)
The big takeaway is that "we saw about a 25 percent expansion of median lifespan of these mice. This held true for two different genetic strains of mice," each engineered with the killswitch tweak, "and was irrespective of sex or the diet," says Baker. These mice also showed delayed cancer onset, fewer cataracts, an increased drive to explore, and various other age-resistant effects in a wide range of body tissues. The body, it seems, is better off without senescent cells.
As far as the researchers could find, there was pretty much just a single downside of eliminating senescent cells: Wounds healed more slowly. That's no big surprise, as senescent cells are known to play a role in healing and scar-tissue formation.
On To Humans?
Jesús Gil and Dominic Withers, two medical researchers at Imperial College London—who were not involved in today's research—applaud today's research and concur with the results. "The removal of senescent cells does indeed delay ageing and increase healthy lifespan," they write in an essay accompanied alongside the research paper in the journal Nature.
So what's next? Well, at the same time today's paper was published, a company called Unity Biotechnology launched, with the stated goal to use today's breakthrough understanding of senescent cells to develop medicines that fight the process of aging. (Obviously they're going to have to use a different approach to genetically engineering humans.)
"Imagine drugs that could prevent and maybe even cure arthritis or heart disease or loss of eyesight. It's an incredible aspiration," said Nathaniel David, Ph.D., CEO of Unity Biotechnology in a press release. "If we can translate this biology into medicines, our children might grow up in a different world than we did. There will be many obstacles to overcome, but our team is committed and inspired to achieve our mission."
I'm looking at a picture of two mice. The one on the right looks healthy. The one on the left has graying fur, a hunched back, and an eye that's been whitened by cataracts. “People ask: What the hell did you do to the mouse on the left?” says Nathaniel David. “We didn't do anything.” Time did that. The left mouse is just old. The one on the right was born at the same time and is genetically identical. It looks spry because scientists have been subjecting it to an unusual treatment: For several months, they cleared retired cells from its body.
Throughout our lives, our cells accumulate damage in their DNA, which could potentially turn them into tumors. Some successfully fix the damage, while others self-destruct. The third option is to retire—to stop growing or dividing, and enter a state called senescence. These senescent cells accumulate as we get older, and they have been implicated in the health problems that accompany the aging process.
By clearing these senescent cells from mice, Darren Baker and Jan van Deursen at the Mayo Clinic College of Medicine managed to slow the deterioration of kidneys, hearts, and fat tissue. The animals lived healthier and, in some cases, they lived longer.
“The usual caveats apply—it’s got to be reproduced by other people—but if it’s correct, without wanting to be too hyperbolic, it’s one of the more important aging discoveries ever,” says Norman Sharpless from the University of North Carolina at Chapel Hill School of Medicine, who was not involved in the study.
Several chemicals can slow the aging process in laboratory organisms, but Sharpless says it's hard to think how people might benefit. “You take a drug—resveratrol, green tea, god knows what—for 30 years, and by the time you’re 80, you’re actually 70. That paradigm doesn’t work in the real world. People hate to take drugs, especially when they don’t know it’s helping them. And no pharma company would develop such a drug. If this paper is right, suddenly you have a way of taking an old organism and making it physiologically younger. You go from a prevention paradigm to a treatment one. That's something you can sink your teeth into.”
Baker and van Deursen started this line of work by accident. In 2004, they found that turning off a gene called BubR1, which they initially thought would be involved in cancer, actually revved the aging process into high gear. The mice got cataracts, developed heart problems, lost body fat, and died much earlier than usual. And they seemed to accumulate many more senescent cells.
In 2011, the team developed a way of singling out and removing those cells. Senescent cells are characterized by a protein called p16. Baker and van Deursen genetically engineered their fast-aging mice so that they would destroy all their p16-bearing cells when they received a specific drug. The results were dramatic: The senescent cells disappeared, and though the rodents still died earlier, they were bigger, fitter, and healthier when they did. Even old mice, whose bodies had started to decline, showed improvements. “Then, the question became: What would happen if we removed those cells in a normal mouse?” says Baker.
“Without wanting to be too hyperbolic, it’s one of the more important aging discoveries ever.”
Using the same technique, Baker and van Deursen took normal middle-aged mice and purged their senescent cells twice a week. This time, the process increased the rodents’ average lifespan by a quarter. And as they got older, they lost less body fat, had healthier hearts and kidneys, developed fewer cataracts, and stayed more active. The team tested large numbers of mice of both sexes, from two genetic strains, and raised on two different diets—and the results were always the same. “This is a real improvement. It’s in real aging; the last paper was in fake aging,” says Sharpless.
John Sedivy from Brown University agrees. “This issue of whether senescent cells contribute to aging has been out there for decades,” he says. “This is the first paper that I’d say is really watertight.”
Senescent cells aren’t idle. They secrete molecules that trigger inflammation and enzymes that destroy connective tissue. “We've identified 50 to 60 different molecules that these cells produce, any one of which has the potential to wreak havoc on tissues,” says Judith Campisi from the Buck Institute for Research on Aging.
This seems perverse, but there’s method to the body’s madness. Cells undergo senescence because they accumulate damage that could potentially lead to cancer, and the molecules they secrete prompt the immune system to come over and clear them. “It’s a very potent anti-cancer mechanism,” says Baker. But as we get older, the immune system falters, and senescent cells accumulate. Now, the molecules they secrete become problems rather than solutions.
Even then, senescent cells have benefits. Last year, Campisi showed that these cells help to heal wounds. And sure enough, Baker and van Deursen found that their mice heal more slowly after such cells were removed.
The worry then is that any attempt to clear senescent cells in people would have serious side effects, as well as obvious benefits. Charles Sherr from St. Jude Children's Research Hospital is also concerned about cancer. Since the p16 protein prevents tumors from arising, Sherr wonders if “the salutary effects that accompany elimination of p16+ cells would be offset later by increased cancer incidence.” Baker and van Deursen saw no signs of that in their mice, but humans live for much longer than rodents.
“There will be tradeoffs for sure, but as we drill down into the biology, we have a better chance of preserving the good side of these cells while eliminating the bad,” says Campisi.
A newly launched company called Unity Biotechnology, which counts Campisi and van Deursen among its co-founders, is working to move the team’s senescence-clearing discoveries to the clinic. “We have spent the last four years identifying a series of Achilles heels that are unique to senescent cells,” says Unity CEO Nathaniel David. “We have molecules that are 300 times more poisonous to these cells than to non-senescent ones.”
His first goal is to use these compounds to treat a couple of diseases that are likely caused by senescent cells and that are localized to specific body parts. Osteoarthritis might be a good target—David has it in his toes—and so might late-stage glaucoma. If that works, “we can start going after higher-risk stuff like healthspan,” says David.
Senescent cells are characterized by a protein called p16. Baker and van Deursen genetically engineered their fast-aging mice so that they would destroy all their p16-bearing cells when they received a specific drug.
Using the same technique, Baker and van Deursen took normal middle-aged mice and purged their senescent cells twice a week. This time, the process increased the rodents’ average lifespan by a quarter. And as they got older, they lost less body fat, had healthier hearts and kidneys, developed fewer cataracts, and stayed more active. The team tested large numbers of mice of both sexes, from two genetic strains, and raised on two different diets—and the results were always the same.
"Say someone came up to you selling a dietary supplement—a pill that you take once a day—that could boost your energy, improve your body’s ability to repair its DNA, and keep you healthier as you get older.
It might sound like a scam, or more likely just another in a sea of confusing, undifferentiated claims that make up the $20 billion dollar supplement industry.
But let’s say that someone is MIT’s Lenny Guarente, one of the world’s leading scientists in the field of aging research. And he’s being advised by five Nobel Prize winners and two dozen other top researchers in their fields. You might pay a little more attention.
The Scientist And The Startup
Cofounding a supplement company seems an unlikely career move for someone like Guarente, a man who is one of the most well-respected scientists in his field. ("It is a departure," Guarente admits). Mostly, for him, getting involved in Elysium Health is a decision born out of opportunity and frustration. The opportunity is the chance to make a difference by translating findings in the booming field of aging research directly to consumers today. The frustration is that doing this has taken so long in the first place.
"My biggest hope is that we can make available to people something that is currently unavailable, and that it will have a positive impact on their health," Guarente says.
Elysium Health actually had its beginnings in conversations between its other two, younger cofounders, Eric Marcotulli and Dan Alminana, who were then tech investors and gym buddies. Even though they’re both quite health-conscious, they knew they couldn’t halt the march of aging and all the ailments that come with it. Far more than diet or anything else people can control, the biggest risk factor for many of the diseases that kill us—including diabetes, cancer, and cardiovascular disease—is simply getting older.
NAD—Nicotinamide adenine dinucleotide—is one of the most compelling bits of chemistry related to aging. Its presence in the body is directly correlated with the passage of time: An elderly man will have about half the levels of NAD is his body as a young person. There’s no amount of healthy eating or exercise that can stop the decline. But in a scientific paper published in 2013 that generated headlines about "reversing aging," Harvard’s Sinclair showed that after a week of giving two-year-old mice a boost of NAD, their tissues looked more like six-month-old mice.
Elysium’s pill is an attempt to replicate that process naturally in humans. It contains the building blocks of NAD, so the body can easily absorb the smaller molecules and synthesize its own. The pill also contains pterostilbene, a compound, that is a close relative of resveratrol, but which Guarente says is potentially more potent and effective.
Elysium explicitly wants to avoid the charlatan feel of the countless "anti-aging" products on the market today. It isn’t selling the pill as a key to a longer life or to preventing any particular disease, since there isn't any evidence the pill will do that. A press release the company put out with its launch hardly mentions aging at all. (Another reason is they want to appeal to young people too, who don’t necessarily care about aging, but may want to feel healthier and more energetic). Instead, the founders talks about enhancing basic biological functions: improving DNA repair, cellular detoxification, energy production, and protein function. We have no interest in being an anti-aging company and extending lifespan," says Marcotulli. "For us this is about increasing healthspan, not lifespan."
Thanks would same the same about your posts; even when I don't agree with you they (your posts) generally tend to be thoughtful and intelligent; not afraid to listen to people who don't always agree with me, you learn more that way. Follow up to my previous post; I actually ordered some of the stuff for myself, will try it for a month or so, will see if I feel any different.Diogenes wrote:Great work Williatw. Appreciate your postings on this and other issues.
I forgot to mention aging reversal. This is a big project both in my lab and in one of our startup companies. This is not about wellness or drugs that affect diseases of aging, which are effects rather than causes; it’s trying to get at the causes of aging and reverse them. And there are a fair number of precedents for this in animals, but the idea is to get it transferred to humans.
Reversal of aging: Some examples of this are if you take blood from a young mouse and exchange it with an old mouse. The small molecules, macromolecules, and cells in the blood result in a variety of biomarkers of aging being reversed. You can affect the vasculature, the blood vessels, the nerves, skeletal and cardiac muscles, and there are measures of these that indicate that it’s not just prolonging a very aged state or going for longevity; you’re actually reversing it.
This is a much better target, in any case, than prolonging longevity because, A, it takes years to decades to even prove that you have extended longevity. Also, if you’ve done it on somebody that’s quite old, the economic consequences are dire; that’s the part of your life where you spend huge amounts on medicine and don’t improve the quality of life tremendously. If you can reverse it to an age where you essentially don’t use any medicine, this will be much more cost effective.
williatw wrote:Thanks would same the same about your posts; even when I don't agree with you they (your posts) generally tend to be thoughtful and intelligent; not afraid to listen to people who don't always agree with me, you learn more that way.Diogenes wrote:Great work Williatw. Appreciate your postings on this and other issues.
Did you read this Instapundit article about aging?williatw wrote: Follow up to my previous post; I actually ordered some of the stuff for myself, will try it for a month or so, will see if I feel any different.
First gene therapy successful against human aging
Elizabeth Parrish, CEO of Bioviva USA Inc. has become the first human being to be successfully rejuvenated by gene therapy, after her own company’s experimental therapies reversed 20 years of normal telomere shortening.
“We hope to see results within the first two to three months."
A groundbreaking trial to see if it is possible to regenerate the brains of dead people, has won approval from health watchdogs.
A biotech company in the US has been granted ethical permission to recruit 20 patients who have been declared clinically dead from a traumatic brain injury, to test whether parts of their central nervous system can be brought back to life.
Scientists will use a combination of therapies, which include injecting the brain with stem cells and a cocktail of peptides, as well as deploying lasers and nerve stimulation techniques which have been shown to bring patients out of comas.
The trial participants will have been certified dead and only kept alive through life support. They will be monitored for several months using brain imaging equipment to look for signs of regeneration, particularly in the upper spinal cord - the lowest region of the brain stem which controls independent breathing and heartbeat.
The team believes that the brain stem cells may be able to erase their history and re-start life again, based on their surrounding tissue – a process seen in the animal kingdom in creatures like salamanders who can regrow entire limbs.
Dr Ira Pastor, the CEO of Bioquark Inc. said: “This represents the first trial of its kind and another step towards the eventual reversal of death in our lifetime.
“We just received approval for our first 20 subjects and we hope to start recruiting patients immediately from this first site – we are working with the hospital now to identify families where there may be a religious or medical barrier to organ donation.
"To undertake such a complex initiative, we are combining biologic regenerative medicine tools with other existing medical devices typically used for stimulation of the central nervous system, in patients with other severe disorders of consciousness.
“We hope to see results within the first two to three months."
I don't see how analogy to Caligula's time is germane to tomorrow, tomorrow being merely 1/∞th of the domain of curing aging's consequences.Diogenes wrote:Betruger wrote: There's no humane justification for denying future generations the well being of longer, less hurried lives.
This perception bothers me quite a lot. Considering the sweep of history, i'm not sure extending lives is necessarily a good thing at all. I can just imagine what a longer lived Caligula might have accomplished.
This notion also reminds me of all the wonderful speculations people had regarding the invention of movies and television. They were to be "great teaching methods", and to used "improve education", and yet they have turned out to be that "Vast Wasteland" that Newton Minow noticed back in the 1960s.
Longer lived humans will likely engage in more extended debauchery and oppression. At least that is the direction in which I would be betting. Have you been noticing what sort of "glitterati" is leading society nowadays?
Strawman. The moon was not quicksand. Futureland type visions are bogus futurology. The future is not simple. Living longer is better. Living in barrels is for suckers. Dying before you feel ready and satisfied with your life is inhumane; it is murder if a remedy exists. CF hippocratic oath; how much political philosophy do docs and nurses impose on patients in exchange for treatment?movies and television. They were to be "great teaching methods", and to used "improve education", and yet they have turned out to be that "Vast Wasteland" that Newton Minow noticed back in the 1960s.
Betruger wrote:Diogenes wrote:Betruger wrote: There's no humane justification for denying future generations the well being of longer, less hurried lives.
This perception bothers me quite a lot. Considering the sweep of history, i'm not sure extending lives is necessarily a good thing at all. I can just imagine what a longer lived Caligula might have accomplished.
Diogenes wrote:Longer lived humans will likely engage in more extended debauchery and oppression. At least that is the direction in which I would be betting. Have you been noticing what sort of "glitterati" is leading society nowadays?
The power of politicians historically, to this day, is the scarcity of self-sufficiency. S-S in material and philosophical terms: how much taxes and how much freedom, etc. Crowd control.Hillary Clinton (or Madonna) would be capable of does give me pause