25% Median Life Extension in Mice via Senescent Cell Clearance, Unity Biotechnology Founded to Develop Therapies
With today's news, it certainly seems that senescent cell clearance has come of age as an approach to treating aging and age-related conditions. Some of the leading folk in the cellular senescence research community today published the results from a very encouraging life span study, extending life in mice via a method of removing senescent cells. This is much the same approach employed in one of the first tests of senescent cell clearance, carried out in accelerated aging mice a few years ago, but in this case normal mice were used, leaving no room to doubt the relevance of the results. The researchers have founded a new company, Unity Biotechnology, to develop therapies for the clinic based on this technology. Clearance of senescent cells has been advocated as a part of the SENS vision for the medical control of aging for more than a decade now, and it is very encouraging to see the research and development community at last coming round to this view and making tangible progress.
Senescent cells have removed themselves from the cycle of replication in reaction to cell and tissue damage, or a local tissue environment that seems likely to result in cancer. Their numbers accumulate with age. Most are destroyed by the immune system or their own programmed cell death mechanisms, but enough linger for the long term for their growing presence to be one of the contributing causes of the aging process. These cells behave badly, secreting harmful signals that degrade tissue function, generate inflammation, and alter the behavior of surrounding cells as well. Near every common age-related condition is accelerated and made worse by the presence of large numbers of senescent cells. We would be better off without them, aging would be slowed by the regular removal of these errant cells, and the therapies to make that possible are on the near horizon.
The mouse lifespan study is the important news here, as it demonstrates meaningful extension of median life span through removal of senescent cells, the first such study carried out in normal mice for this SENS-style rejuvenation technology. This sort of very direct and easily understood result has a way of waking up far more of the public than the other very convincing evidence of past years. So it looks like Oisin Biotechnology, seed funded last year by the Methuselah Foundation and SENS Research Foundation to bring a senescent cell clearance therapy to market, now has earnest competition. Insofar as the competitive urge in business and biotechnology speeds progress and produces better results, let the games begin, I say.
Scientists Can Now Radically Expand the Lifespan of Mice - and Humans May Be Next
Researchers 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."By rewriting a tiny portion of the mouse genetic code, the 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, the team reported what happened when the researchers turned on that killswitch in middle-aged mice, effectively scrubbing clean the mice of senescent cells.
Naturally occurring p16Ink4a-positive cells shorten healthy lifespan
Senescent cells accumulate in various tissues and organs over time, and have been speculated to have a role in ageing. To explore the physiological relevance and consequences of naturally occurring senescent cells, here we use a previously established transgene, INK-ATTAC, to induce apoptosis in p16Ink4a-expressing cells of wild-type mice by injection of AP20187 twice a week starting at one year of age. We show that AP20187 treatment extended median lifespan in both male and female mice of two distinct genetic backgrounds. The clearance of p16Ink4a-positive cells delayed tumorigenesis and attenuated age-related deterioration of several organs without apparent side effects, including kidney, heart and fat, where clearance preserved the functionality of glomeruli, cardio-protective KATP channels and adipocytes, respectively. Thus, p16Ink4a-positive cells that accumulate during adulthood negatively influence lifespan and promote age-dependent changes in several organs, and their therapeutic removal may be an attractive approach to extend healthy lifespan.
Unity Biotechnology Launches with a Focus on Preventing and Reversing Diseases of Aging
Unity will initially focus on cellular senescence, a biological mechanism theorized to be a key driver of many age-related diseases, including osteoarthritis, glaucoma and atherosclerosis. "Imagine drugs that could prevent, maybe even cure, arthritis or heart disease or loss of eyesight. It's an incredible aspiration. If we can translate this biology into medicines, our children might grow up in significantly better health as they age. There will be many obstacles to overcome, but our team is committed and inspired to achieve our mission. This has been a long journey, and we're at the point now where we can start making medicines to achieve in humans what we've achieved in mice. I can't wait to see what happens as we move into the clinic."
To close this post, and once again, I think it well worth remembering that SENS rejuvenation biotechnology advocates and supporters have been calling for exactly this approach to treating aging for more than a decade. That call was made based on the evidence arising from many fields of medical research, and from a considered perspective of aging as a process of damage accumulation, one that can be most effectively treated by repair of that damage. The presence of senescent cells is a form of damage. SENS was not so long ago derided and considered out on the fringe for putting forward that position, but for several years now it has been very clear that the SENS viewpoint was right all along. I strongly encourage anyone who remains on the fence about the validity of the SENS proposals for the treatment of aging to reexamine his or her position on the science.
I'm just a layman but I try to read as much as I can here, and this announcement seems like it could be a big one. 25% life extension in a mouse is not nothing.
@Deleo: Mice do better than 25% with calorie restriction. Humans don't of course. That the effect is robust is more important, I think.
So this is big not for the degree of life extension, but rather for the rest of what this effort represents: a venture backed startup with big names doing SENS research and development in a very public way, and pushing the SENS line into the media via their university and venture capital PR machines, as well as one of the first life span studies in normal mice for a SENS rejuvenation biotechnology. This is the beginning of a new phase of growing publicity and mindshare for the SENS repair approach to aging.
That in turn means more funding for research, and a more determined effort to control aging through medicine, one step at a time.
There was a couple comments on reddit about this, and I wanted to see if they were spot on or not.
"I just want to make a quick point about what this paper is and is not.
This paper does not have a method to reduce aging in humans. Baker et al. used a transgenic mouse model that kills senescent cells when a drug complex is added. You can drink the drug all day, but because you don't have the transgene it wouldn't do anything for you.
What this paper does, though, is still important. This paper confirms loads of previous research that increased senescent cell accumulation through aging has a direct effect on quality of life. This research has been suggested before using cell cultures and in artificially aged mice, but this is the first time that a naturally-aging model has been used.
It's important because it finally gives researchers a bigger platform to argue for more senescent-cell-associated research. There are tons of age-related and non-age related diseases that can benefit from this paper. It's extremely important for future funding and research.
TL;DR No you can't do what Baker, et al. did and live to be over 100, but scientists now can ask for more funding to find out how you can."
And
"The ideal application of this research is to develop a long-term medication that can be taken post development (approx. 20ish years old) that passively clears senescent cells throughout a person's life.
A late stage treatment may help with some inflammation associated with the senescence-associated secretory phenotype (increased inflammation, MMPs, etc.) but it likely won't be as effective as preventing the aging-related damage in the first place."
I also thought this was an interesting comment:
"It's going to be along road to get this to actually help humans. They had to change the DNA of the mouse pre-development/conception. As of right now, there is no way for these results to help any human already living or conceived.
Let's hope that further research can figure out a way to get the same results with a different method."
So perhaps we're still a ways away from anything beneficial. Still, hopefully this attracts a decent amount of attention and funding.
&Ham: I imagine that what I assume here to be germline gene therapy is not necessarily needed: if the dasatinib / quercetin combo works in humans like it does in mice the end result should be the same.
@Ham: The startup is venture funded, which means the people involved most likely think they are only a year or two away from therapies that will work in people, ready for trials to begin. VCs are not patient, and would be unlikely to put money in if the horizon was longer than that.
Hm, interesting. That's a good point on the VC. I'm going to follow the r/science thread for a bit too, since that seems to be a bit more grounded than futurology. But I do hope you're right, and it come fairly quickly, especially because they still basically need to find a way to get it working in humans, and who knows how long that could take..
Interesting, here is a quick article on Unity Biotech who will be trying to commercialize this research:
http://www.bizjournals.com/sanfrancisco/blog/biotech/2016/02/unity-biotechnology-aging-calico-senescence-goog.html
Right f****ing on!! Thanks, Reason.
To be clear, they're claiming a 25% increase in median LS, not maximum: a substantial decrease in midlife mortality, but still lights out for everyone by their genetic fate. This is as you'd predict, based on the principle of the "weakest link in the chain": to move the needle on maximum lifespan, you have to push back on all of the cellular and molecular damage of aging, not just one form.
One caveat is that actually, the untreated mice lived a little bit shorter than they "should" have by historical precedent, and the treated mice only lived as long as they "should." The authors attribute this, not unreasonably, to the stress of being grabbed and injected with the drug that activates the INK-ATTAC "suicide gene" twice a week from early middle age until the day they die.
Deleo: Unity Biotech is actually a separate company. Happily, as Reason notes, there are now several players in this exciting space.
@Reason: I was about to underline that *not* because VCs have invested means human trials are anywhere that close - we're still talking biotech after all.
But then, upon reading the article mentionned by Deleo, I spotted the following:
"So 20-employee Unity now has a potential drug that David [the CEO] said could land in human clinical trials within two years, venture cash, respected executives, intellectual property blanketing cellular senescence (...)"
So who knows... it's a good surprise to read this, but let's not forget that CEOs often try to play the optimistic card.
What is the thinking (or evidence) behind the following sentence?
"A late stage treatment may help with some inflammation associated with the senescence-associated secretory phenotype (increased inflammation, MMPs, etc.) but it likely won't be as effective as preventing the aging-related damage in the first place."
Also, my understanding is that a 25% increase in median life span would bring us up to 100, which would mean a reduction of mortality at very old ages too. Unless what they mean is that 62% of the population will get to age 80 (as opposed to 50%) and then die shortly after according to current mortality rates at 80+.
Michael,
When you say move the needle on maximum lifespan, do you mean the current maximum that we've seen, being 122? Or do you mean if you were going to die at 82 because of your genetics, then it's still going to be 82, for example?
Barbara: a 25% increase in median life span would not likely bring us up to 100: our current population median lifespan is already artificially lengthened by medicine, from vaccines (which also impact late-life mortality by reducing lifelong inflammatory burden) to more obviously late-life medical interventions. You have to seriously discount the effects of any intervention that only affects median LS in mice, though less so in a case of actually repairing aging damage than one affecting environmental or metabolic risk factors driving "premature" disease (obesity, inflammation, cardiovascular risk factors, environmental toxins, etc).
Ham: I mean both ;) . Ms. Calment was lucky enough to have genes for slow aging, to not have died in infancy, and live most of her adult life in the 20th century. The average person would still die around 82, because that's what the average person's genetics permits in the miraculous age of medical science.
Now we work toward a whole new class of medical miracles.
Barbara, maybe there'd be too much accumulation (which would have caused too much damage) in an old body for the treatment to be maximally effective?
Then I wonder whether we'd get a better idea by clearing senescent cells in mice that receive the same medical care (anti-cancer etc) as humans. So, they could establish a baseline and then see how much one can add with different repair strategies.
Although of course there are a number of caveats since mice can be cured from cancer at higher rates, they don't suffer from some of our diseases, they are sensitive to being handled (if grabbing them can shorten their lifespan through stress, the mouse version of standard human medical care may do the same), so I guess that increases in maximum lifespan are indeed the only reliable indicator that an intervention is impacting age-related mortality.
@Nico: I found this from an article on the 2011 study on prematurely aged mice:
"In mice that were treated throughout their lifetimes, researchers said they saw a remarkable delay in the development of cataracts, muscle wasting and the type of fat loss that, in humans, causes skin wrinkling. Another group of mice was treated in older age, after cataracts had already set in. The drug didn’t reverse the age-related changes that had already occurred, but it prevented further decline".
But if senescent cell clearing does not reverse senescent cell-caused disease, shouldn't the approach be considered an aging delayer rather than a repair strategy? Even if cataracts etc have multiple causes (e.g. amyloid), shouldn't getting rid of senescent cells improve the situation somehow?
Alternatively, some of the SENS approaches could be considered as therapies that slow aging when taken in isolation and repair strategies in earnest only when used in a treatment package.
Fulltext: https://www.dropbox.com/s/bl2inz7eyrchsre/2016-gil.pdf https://www.dropbox.com/s/cpgfw89wq852imq/2016-baker.pdf
Great news. It looks like therapies for the clearance of senescent cells, along with therapies for the clearance of extra-cellular junk, will be the first true anti-aging therapies available.
I think that in combination with periodic replenishment of stem cells, we could see a big impact on life expectancy. We need to be able to produce "young" patient matched stem cells in high quantities on demand, however.
Michael,
Thats where I get held up a bit. Let's say this translates into humans, and you're able to be 25% healthier, longer. Wouldn't that push you past 82 due to the better health? Or do you think with this, you'll just get sick at 81, and die at 82, as opposed to getting sick at 74 and dying at 82?
@Barbara: Thank you for digging this up. You're making a good point but given my feeble knowledge I wouldn't be able to give you an educated answer. Hopefully Michael or others can shed some light on this.
At the very least, this seems like another report supporting the position that a true rejuvenation treatement must be comprehensive (i.e. the SENS approach, which Michael reiterated here); using a single type of treatmen will only delay or stabilise.
@Ham: I was also confused by Michael's wording, which I have to read back and forth.
I think what Michael meant was that there is no hope of going past 82 with any of the current medical treatments available today - including this upcoming senescent cells clearance method which we're discussing.
Basically those 25% gains are worth nothing as long as they aren't included in a comprehensive, multi-approaches treatment. So those 25% are worth 0% as of now.
@Nico
That doesn't make any sense saying that currently available anti-aging therapies can't get the average lifespan above 82. The average lifespan of people who follow certain lifestyles is 84 in men and 86 in females. Meaning even before you add it currently available medicine which slow AGE accumulation or medicine which cut the risk of cardiovascular disease you can get above 82.
Aren't these drugs called "Senolytics" as reported by Mayo and Scripps Research in March of 2015? The combination of Quercetin and Dasatanib (A cancer drug.) were found to increase lifespans of mice and this drug combination was reported to be a "Senolytic" agent, also by clearing dying Senescent Cells. Also, AP20187 Drug is also a Senolytic.These discoveries are leading the way in the possible improvement in life and health-spans in humans. Bring it on, regardless of the many names these wonder drugs will be called.
@Ham, Nico, and others, there's a problem in comparing mice to humans. You can't translate lifespan changes directly, because we already have a variety of improvements in our biochemistry that mice lack. Essentially it is easy to get double digit increases in median LS (and even max LS) in mice, but a lot harder to move the needle in longer-lived species like us. That said, I think that senescent cell clearance is going to be important in humans. There is already at least one person at Longecity who's tried Dasatinib/quercetin. He has observed peeling of cutaneous lesions that suggest the treatment worked as intended. With more than one company trying to commercialize senescent cell clearance and existing drugs that work at some level, I think the future is bright on this front.
Hi,
This is really great news. Some wondered if this would translate into meaningful gains, I believe it may help but it will be therapeutic in nature (it will reduce inducible senescence (pathological aging) because SASP is inflammation-excess state). Senescent cells secrete inflammatory cytokines (TNF-alpha and IL-6) that help drive pathological advancement of disease. Senescence cell clearance, like senolytics gives, 15-30% improvement in Average Lifespan and Healthspan, but nill on Maximum Lifespan extension. Maximum Lifespan (MLSP) extension is only through total damage removal or delaying. Thus, humans having senescent cell clearance will die before 122, and no later than ~122.
The reason for that is because you have to account Total Damage Accrual from a point in the person's life. Total crosslinks, total protein carbonyls, total AGEs, total amyloid, aggregate, adducts, mtDNA oxidative lesions, total lipofuscin, total oxidized redox disulfides, total lipid peroxidation chain propagation by aldehydes and propagators (MDA Malondialdehyde/TBARS, 4-HNE, Acrolein), total giant senescent mitochondria and a crap load of others.
These damages reduce the body's functioning and brings gene network dysfunction/unstability.
Studies on MLSP demonstrated replicative senescence is caused by telomere loss, and telomere loss is - not - a clock counter but rather a dysfunction marker. By size, it is a marker. But, it is not a clock, that 'counts down' per se. Short telomeres equals demethylation and instability. One study demonstrated that mitochondrial DNA loss dictates rate of telomere loss and MLSP. And the level of substrate respiration (state 3, state 4, glutamate/malate/succinate) mitochondrial innermembrane ETC Complex I Reactive Oxygen Species production (ROS, super oxide and hydrogen peroxide (H2O2) transformed to hydroxyl radical through iron-Fenton reaction) is what drives this. Also called OXPHOS Complexes (Oxidative Phosphorylation) that make redox NADPH be used as electron donor through ETC and allow mitochondria to produce cell energy ATP.
That is also why mitochondrial innermembrane phospholipid fatty acids PI (Peroxidizability Index) and DBI (Double-Bond Index) is causal to MLSP. Mitochondrial Innermembrane is right next to mtDNA. High PI and DBI equals short lifespan MLSP despite mitochondrial Glutathione and Thioredoxin trying its best to scavenge membrane Hydroperoxides formation from hydroxyl radical stealing hydrogen atom from unsaturated fatty acids (initiating lipid peroxidation propagation forming highly mutational reactive aldehydes (MDA, MDA-TBARS), alkenals (4-HNE), methylglyoxals (creating glucosepane, MDA-Lys, CML, pentosidine, CEL, furosine from Amadori).
All of this damage damages extremely precious mitochondrial DNA, which make the mitochondrias dysfunctional, clogging lysosome for mitophagy, and being incapable of keeping mitochondrial membrane potential (leading to Cytochrome C loss through mitochondrial permeability pores) and mitochondrial ATP OXPHOS respiration. Soon the cell becomes senescent as she loses nuclear chromosome telomeric DNA.
That means to go above Maximum Human Lifespan, these damages must be completely blocked
- from Early Age Only - (starting from Total Damage Accrual in young age only), either through mitochondrial membrane protection against mitochondrial ROS production via redox chemistry, membrane PI DBI phospholipid modulation of hydroperoxide formation, mtDNA replacement or by removal of damages as they come (abating/delaying).
What works in mice, doesn't always work in humans. Just because this strategy improved healthspans and lifespans for mice, doesn't mean it'll work in humans, or to the same degree. And they still have to discover and test drugs that can do this for natural-born adult humans; the mice used in this study were genetically engineered. Maybe it's just not possible to do this in an adult human, and instead will only work for designer babies that were genetically engineered from the get-go. And even if they manage to develop a drug that can eliminate senescent cells in an adult human body, it's going to take many years to put it to market. And it might not work on those who are already middle-aged or older. It might only be beneficial for those who are already young.
Don't get your hopes up.
@MissKaioshin
Always trollin it seems. Looks like you just copied and pasted your response from reddit to fightaging. It makes me wonder why you spend your personal time that way. There was a study on trolls posted on reddit a while back and how it makes them feel better. I can't remember if it was the attention they receive as they don't feel valued in their personal lives or if it was they feel more powerful online being able to have an effect on people whereas in their personal life they feel helpless. I am naturally curious so I am going to have to look it up and see what conclusion they found. Anyways best of luck with your trolling.
BTW if it is depression there are many articles on r/Nootropics regarding how to increase your BDNF which helps with depression. Also selegiline definitely has helped a lot of people and it likely extends lifespan. Of course talk to your doctor before you try anything.
@CANanonymity
Looking at treatments possible in the next 5 years, I think that a treatment for senile systemic amyloidosis, telomerase gene therapy, and thymus rejuvenation, in addition to the anti-aging therapies that are already available, would be able to allow some of the supercentenarians (110+) to be able to make it past 122.
The way I see it statistically if you decrease all causes of aging by 20% than you should have a parallel move in mortality rates to the right by 20%. Similarly to what happened in C. Elegans when they paused epigenetic drift.
One thing that I think is important to point out, and that actually makes the results that much more impressive is that while the treatment successfully killed heart, kidney, eye, and fat senescent cells, it failed to kill senescent cells in the colon and liver(and possibly other organs?). So it's possible we would see even more impressive results if we can successfully target those cells as well. Anyone want to speculate as to why the treatment failed in those organs? My best guess would be that the senescent cells in these organs don't secrete p16 or at least secrete a lot less of it then the senescent cells that were successfully targeted. When you look at this research and the past research in the field, it seems pretty clear that there's unlikely to be a one size fits all drug, but instead different drugs targeting different senescent cell profiles.
MissKaioshin is a troll simply ignore them they clearly are depressed. Let us move beyond the opinion of someone not working in the field and discuss the actual facts of the matter rather than waste time with negative speculation.
The MMTP has been in discussion with Oisin Biotech and I believe their solution to Senescent cells is promising and offers an alternative to small molecule approaches such as Scripps/Mayo are mining. If all goes to plan we will work with Oisin this year and get them some useful data.
Meanwhile we will apply life and health studies to D&Q at Leipzig University. Ultimately we want to combine senolytics with other approaches eg, stem cells. I am frequently seeing these interventions are increasing lifespan ~18% so it seems obvious to reap greater increases we need to combine approaches.
Let us Hope Yale shortly finds some candidate AGE cleavers which we can test and combine too.
@Empirical: You're making a good remark, there's still room for improvement in this treatment alone.
@Empirical
Yes this appears to be exactly the case. Certain small molecules in particular have affinity for particular types of cells. A combination of D&Q worked on liver cells for example:
"A single dose of D+Q (D: 5 mg kg−1 body weight and Q: 50 mg kg−1 by oral gavage here and in the following studies), a drug ratio that was most effective in senescent MEFs (data not shown), reduced SA-βgal+ cells (Fig.(Fig.3C)3C) and p16 mRNA (Fig.(Fig.3D)3D) in fat from old mice within 5 days. D+Q also reduced p16-positive cells in liver from old mice (Fig.(Fig.3E-F).3E-F). As with AP20187, the drug that activates selective killing of cells expressing p16 in transgenic INK-ATTAC mice (Baker et al., 2011), not all senescent cells were removed by D+Q., yet functional improvement was seen"
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4531078/
Now it seems likely we will find other Senolytics that favor other cell populations and one could in theory create a combination or regime that could be used to target more cells. Or the other approach is something like Oisin is using which is potentially more flexible in how it works and with less chance of off target effects. I cannot elaborate on that as this is something Oisin would need to explain. Needless to say there are solutions and we will be testing them to see what the data shows be it positive or negative for lifespan.
If you want to keep track of what we are doing visit us at http://www.majormouse.org
Very good news :D
Oh I meant to say MMTP aims to launch a fundraiser on lifespan.io mid March, we will have a press release soon and will escalate our presence very shortly. We are also keen to engage with the community so if you run a longevity/scientific blog or group get in touch if you would like to do an interview about our work or perhaps an article. info@majormouse.org
Glad to hear about your upcoming plans, Steve! I'll be waiting for your fundraiser.
It's hard to believe that this research had to be funded philanthropically by the Paul F. Glenn foundation because the National Institute on Aging rejected Kirkland and van Deursen's research grant back in 2011 as one of three reviewers thought that "senescent cells were too rare to do much damage".
http://www.nytimes.com/2011/11/22/science/research-on-senescent-cells-is-denied-nih-grant.html
If the Glenn foundation hadn't stepped in this research could still be stuck at the point it was back in 2011 - a demonstration in a mouse model that accumulated senescent cells more rapidly, and could be stuck there for an indefinite period.
Well done to the Glenn foundation, and well done to the SENS Foundation for funding similar breakout research in other 'stuck' areas.
I still can't believe that the SENSRF are the only people investigating allotopic expression of mitochondrial genes (bar the ND4 gene being commercialized by Gensight and also Spark Therapeutics).
@Santi
Hi Santi !
I should have been more precise when I meant no increase of maximum lifespan in elders but only young. Like you suggested supercentenarians getting the combined therapies could indeed go above MLSP of 122. But, because they are supercentenarians and have accrued the highest damage load (and that is where I should have been more precise), the supercentenarians actual lifespan extension - above - 122 years MLSP will be rather small, say, about an extra 30 years whih would allow them to reach ~150 years old. With luck, they might make it to 160-175 years old (the age of giant tortoise) because they may have found supercentenarians who supposedly beat Jeanne Calment's 122 years and 164 days MLSP standard. Like recently a still living Brazilian centenarian man claims to be 131 years old. He is being sought by Guiness World records for oldest human ever and his government (late 1800s birth certificate act visa papers) to verify the validity of his claim. Same goes for a living Haitian centenarian woman claiming to be 120 years old, thus current oldest human 2 years shy from beating Jeanne Calment's record, who immigrated from Haiti to here where I live. Thus, these superextracentenarians above 120 have a chance of, at most, 50 years extra, making them reach 175 tops by using all combined biorejuvenation therapies starting from massive Total Damage Accrual at their extra-late age stage.
This is in total contrast with Young people, who have very low Total Damage Accrual so far in their young life, who will benefit exponentially from all combined therapies. As Aubrey de Grey said, and his longevity velocity escape paper showed, young people (below 40 years old) will have the chance to reach dramatically higher MLSP : we are talking about 350 years and higher, Many Centuries Lifespan, and de Grey went on to go say as far as 4-digit lifespan (a 1000 years old !).
That is something impossible for the - already - and current extremely aged elder population between 80 and 120 years old. Simply by the fact of their too-lateness point in life and massive Total Damage Accrual from the long life they lived up till now. It will be extreme 'Catch-Up/Patch-Up' damage accrual game in centenarians, impossible to win at it.
A Technology Review article which further confirms that this approache dates back from 2011: https://www.technologyreview.com/s/600705/in-new-anti-aging-strategy-clearing-out-old-cells-increases-life-span-of-mice-by-25-percent/
Part of the article stuck out to me:
"Developing an anti-aging treatment also remains difficult because the FDA does not recognize aging as a disease. And since humans live longer than 70 years on average, a clinical study would take decades"
How would this development (and whatever drug or therapy they devise for humans) move from the lab and into trials, without it taking decades, like the author here proposes? Just check for better and increased health?
@Ham: maybe they could look at mortality at each age. In a few years they would also be able to see whether there are any accrued benefits, e.g. whether death rates at 70 in someone who started taking the drug at 65 are the same as death rates in someone who started taking the drug at 69.
I was thinking something along those lines, most likely. Though, the FDA has to be willing to accept it for a clinical trial to treat something first (which is why I think the metformin trial is so important), so we'll cross that bridge when we get there, I suppose.
Unity Biotechnolgy are going to test their senolytic drugs first against osteoarthritis and glaucoma. I think they will then try to expand the approval to general 'aging'. Alhtough I imagine there will be a triving off label use market in the interim.
The other good news is that the FDA recently gave approval to the group using metaformin to treat aging. Although that study probably won't achieve much in terms of results (it is slowing damage rather than removing it) at least it has cleared the way for Unity and other companies.
I found this article talking about this recent news. What do you all make of it?
https://www.crsociety.org/topic/11541-does-killing-senescent-cells-really-extend-rodent-lifespan/
@Ham: Michael already addressed that. The short lifespan of the controls is probably caused by the stress of being injected twice a week for half of their life. Humans will not have that problem.
He also address the maximal lifespan issue.
And, about the genetic engineering issue, everybody knows that this treatment can't be directly translated to humans. The importance of this study is that it demostrates that normal senescent cells levels shorten median lifespan, and thus, any therapy that removes them (whatever the method it uses) is a good (part of an) antiaging therapy.
@Michael said "To move the needle on maximum lifespan, you have to push back on all of the cellular and molecular damage of aging, not just one form." Are you sure about that? There have been demonstrated instances of Max lifespan in mice being increased by methods that (presumably) only addressed part of the damage of aging, like Mt damage. See:
https://www.fightaging.org/archives/2009/08/a-list-of-interesting-longevity-enhancement-methods-in-mice.php
KC: see my comment on that post, dated April 21, 2011 1:14 PM ;) .
The part about the controls' short lifespan being due to the stress of the injections is pure conjecture by the researchers. A big part of the attention this paper is getting is riding on that conjecture.
It seems unlikely that this is the first mouse study where the mice got injected twice weekly, so there should be other studies that we should be able to compare the controls against to at least have any confidence on that explanation.
@Michael. Thanks for replying. Read your comment. I readily admit your understanding of study methodology is superior to mine. (Though I'm surprised so many studies are flawed) And the idea of having to push back on all aging damage to affect max lifespan makes sense logically (To use a clunky analogy, even if the car's engine has a longer lifespan the car won't work for a much longer time period if the battery's lifespan remains unchanged.)
Given this, I assume it would have to mean those max lifespan extending interventions you mentioned that work in normal mice (CR, Met Restriction, GH Knockout, IGF-1 and Insulin Signalling Manipulation) reduce ALL major forms of fatal aging damage?
Still, since senescent cells affect so many tissues, I'd think/hope you might see a greater impact on mean LE from senescent cell clearance than some other interventions.
Hello everyone. Glad to be here. This is some interesting piece of research to be sure.
I can also see some interesting SF literature in the comments section.
What eludes me in this discussion though, is why everyone is getting so excited about this 25% increase in median life expectancy of mice, when one quick look through Wikipedia would show, that apparently there is a guy called Jake Perry, who managed to successfully keep a cat alive for 38 years, which is TRIPLE the average lifespan of a cat. And this result has proven to be repeatable to a certain degree, since another cat kept by the same man, has reached 34 years which is more than double the average.
25% increase in median lifespan, don't get me wrong. I'll take it any day. But it's not a record breaking achievement.
@Misiu: This is a result about median lifespan of a population, nothing to do with the lifespan of a single individual. As for the importance of the size of the increase, it is already explained in the second comment.