SENS has funded a lot of really great research in the field, which you can view here.
Lifespan is involved in advocacy, and have been successful in hosting conferences and providing a platform for information sharing in the field. They have also crowdfunded some research.
Both the research and advocacy components are crucial for helping to expand the longevity field.
(2) Complexity of aging
Yes, the causes of aging are complicated—that is, how the damage accumulates—is complicated. But treating aging doesn’t actually require understanding how the damage accrues, using the SENS (strategies for engineering negligible senescence) approach. It only requires how to ameliorate the various types of damage (hallmarks of aging).
Bear in mind that overwhelming evidence in the past 20 years has suggested that all aging-related processes are, looking upstream, a result of the hallmarks of aging and that there is no other cellular phenomenon besides these 7-10 processes (depending on how they are classified) responsible for the aging process that cannot be reduced to them. In the past 20 years, no new hallmarks have been discovered and researchers are fairly confident that these are the only hallmarks there are to discover.
“The basic point we’re making there is to contrast the regenerative approach with the more traditional idea of trying to make metabolism create molecular and cellular damage more slowly. In order to do the latter, we would need to understand our biology massively better than we do at present, so as to avoid creating unforeseen side-effects. By contrast, with the regenerative approach we don’t need to know much about how damage comes about: it’s enough just to characterize the damage itself, so as to figure out ways to repair it. We’re effectively sidestepping our ignorance of metabolism. Rejuvenation biotechnologies are simply regenerative therapies that pre-empt the diseases and disabilities of old age. They consist of molecular, cellular or whole-organ interventions that restore the structure of the target to something like how it was in early adulthood.”
Bear in mind that overwhelming evidence in the past 20 years has suggested that all aging-related processes are, looking upstream, a result of the hallmarks of aging and that there is no other cellular phenomenon besides these 7-10 processes (depending on how they are classified) responsible for the aging process that cannot be reduced to them.
Is there any polling about how many of the anti-aging researchers believe this thesis?
To the best of my knowledge, there has not been polling of this question to anti-aging researchers (geroscientists) specifically.
However, if you watch lectures by anti-aging researchers, and the major conferences such as ARDD, EARD, CSHL Mechanisms of Aging and so on, most of them seem to use this paradigm when discussing aging and many even have a slide on the hallmarks of aging. All of the big names such as David Sinclair, Brian Kennedy, Lynne Cox, Judith Campisi, Alex Zhavarankov, and many others all mention the hallmarks of aging.
If you want further evidence, consider that the original paper, The Hallmarks of Aging (2013) published in the journal Cell is the most highly cited academic paper in the entire field—with over 6800+ citations. Although it was Aubrey de Grey who first conceived of the Hallmarks (which he called the ‘7 deadly SENS’ and categorised them slightly differently in his 2007 book, Ending Aging) it has now become the framework used by researchers in the field, and even included in academic courses—such as the lectures I was invited to give to clinical neuroscience students here at Oxford University about aging and neurodegeneration.
So it’s fair to say that it is now the consensus that the hallmarks of aging is the predominant view of the field, even though this was not the case 10-15 years ago when other theories of aging such as the free radical theory of aging held more weight.
such as the lectures I was invited to give to clinical neuroscience students here at Oxford University about aging and neurodegeneration.
If you are in a position to be invited to such talks, it might be worthwhile to put information about your identity into your post. Maybe as part of a epistemic status tag on the top.
The thing that’s very unclear to me is why SENS has so little funding if that’s framework is now consensus.
It seems like while the metformin trial study seems like good value for money in contrast to typical NIH funding, funding it with a decade worth of SENS funds wouldn’t be good value for money if SENS works. Why doesn’t SENS succeed at having a 8 or 9 figure budget? Which arguments are keeping the billionaire money from funding it stronger while the metformin trial study did get it’s money?
Which arguments are keeping the billionaire money from funding it stronger while the metformin trial study did get it’s money?
I guess one reason is that billionaires don’t have time to do their research in detail, to see for themselves whether de Grey and Sens are worthy, but rely on reputation and opinions of popular names in the field. And the reputation of SENS seems to have suffered a bit initially, when many scientists found their proposals for rejuvenation too bold or futuristic https://en.wikipedia.org/wiki/Aubrey_de_Grey#Criticism
SENS Research Foundation aren’t the only source of funding for research into the hallmarks of aging. The research into the hallmarks of aging labs at NUS, the Buck Institute, Oxford, Harvard and many other institutions is largely funded through the traditional route of national medical research councils. SENS Research Foundation funds some of the research, but by no means most of it. That said, they have a good track record of selecting some of the most important projects to fund despite a small budget of $5-10 million. For a point of comparison, the National Institute of Aging which as a $3 billion budget allocates around $100 million to geroscience.
The thing that’s very unclear to me is why SENS has so little funding if that’s framework is now consensus
Because they choose the most neglected (long-term/difficult/high-risk high-reward) projects within the Hallmark framework (I talked extensively about this in my posts if you want to take a peek).
Why wouldn’t billionaires (outside of Thiel and Greeves) that donate money for improving health outcomes want to fund long-term/difficult/high-risk high-reward projects?
Do you know whether SENS request a grant from OpenPhil?
Yes, and there are some signs that more billionaires (at least, the progressive-minded ones) are taking this seriously. For example, Elon Musk in an interview 3 weeks ago (timestamp: 24:03) mentioned the feasibility of ‘stop[ping] aging’ when asked about the biggest threats to the future of humanity, for the first time on the public record.
Our program officer Nick Beckstead offers the following forecast to make the above more precise/accountable: By January 1, 2067, there will be no collection of medical interventions for adults that are healthy apart from normal aging, which, according to conventional wisdom in the medical community, have been shown to increase the average lifespan of such adults by at least 25 years (compared with not taking the interventions). (Subjective probability: ≥93%)
However, I would strongly disagree with this timeline, based on my knowledge of the field, today. I would go so far as to say that some combination of therapies available today—including metformin, senolytics, blood plasma exchange and epigenetic reprogramming—could already extend lifespan 25 years (compared to not taking the therapies) if personalised and multi-omics-biomarker-optimised. It’s just that we need more research to know how, when, where and how much of these therapies are required for each individual. With another 46 years of research in a field that is already expanding, I have no doubt that 25-year lifespan extension will be available by 2067.
They also made a big mistake, in my opinion, by overevaluating the amount of funding that geroscience (i.e. research that is relevant to the development of anti-aging therapies) receives:
The NIH reports spending $2.7 billion per year on aging research in 2015.16 In the 2015 budget request, $510 million per year is tagged as “neuroscience” and $177 million per year is tagged as “aging biology.”17 We have heard in various conversations that this research is mainly relevant to addressing particular symptoms associated with widely-recognized diseases (e.g., Alzheimer’s disease), rather than on understanding the basic mechanisms that cause aging. This is plausible to us, but we haven’t seen any convincing evidence for it and we do not take it for granted.
It is clear to almost everyone working in the field that the amount of funding going towards geroscience—i.e. targeting aging therapeutically—is drastically lower than that of age-related diseases—which employ completely different research methods and experimental protocols (i.e. do not perform lifespan studies with geroprotective interventions prior to disease onset). A list of most of the researchers working in the field is here (last updated April 2020) though I don’t think OpenPhil cared to look deeply enough into the field to recognise the lack of researchers and funding for geoscience in particular.
There are other flaws in their analysis. For example, they mentioned the large funding that Google-backed Calico receives, here:
Some aging-focused companies working in this area that we became aware of in the course of this investigation include Calico ($500 million in disclosed investment and agreed upon potential for $1B more);24
However, as Aubrey de Grey explains in this interview, Calico—despite having a huge budget—have a poor organisational structure that has so far precluded any meaningful research advances in the field.
As Aubrey de Grey puts it in the interview (from ~1:14:00 onwards):
They [Calico] have created a vast valley of death internally....they’ve got this paradise of research where they’ve hired fanastically good researchers in large numbers paid large salaries to find stuff out; to increase our understanding of what aging is. And on the other end they’ve got these people who know all these people who know all about how to turn proof of concept into a product—and they’ve got zero in the middle. They’ve got nothing that turns knowledge into proof of concept.
So overall, I believe OpenPhil are inaccurate in their assessment of the geroscience field based on their ‘medium’ depth investigation into it. There are numerous other examples of statements in their write-up that demonstrate a poor or incomplete knowledge of the state of the field—both scientifically and economically. I can go into these if you like, and I’ll probably write up a post about this in the future.
Youtube allows you to link to specific timestamps when you click on the share button.
Yes, and there are some signs that more billionaires (at least, the progressive-minded ones) are taking this seriously.
I think there are two separate issues. One is about aging being taking seriously and the other is about SENS being taken seriously.
However, as Aubrey de Grey explains in this interview, Calico—despite having a huge budget—have a poor organisational structure that has so far precluded any meaningful research advances in the field.
I think you have the wrong link. In any case Aubrey de Grey basically here that hiring credentialed people is not enough to get results but that if he would organize the research it would produce better results. While that might be true it’s hard to assess.
I would go so far as to say that some combination of therapies available today—including metformin, senolytics, blood plasma exchange and epigenetic reprogramming—could already extend lifespan 25 years (compared to not taking the therapies) if personalised and multi-omics-biomarker-optimised.
That sounds like the people in the 1970s that they thought they could cure cancer by the end of the decade if they declare war on it.
Youtube allows you to link to specific timestamps when you click on the share button.
Thanks for the tip.
I think you have the wrong link. In any case Aubrey de Grey basically here that hiring credentialed people is not enough to get results but that if he would organize the research it would produce better results. While that might be true it’s hard to assess.
Sorry, here is the link. It’s not that hard to assess, given he has many informal chats with people affiliated with Calico. His point is that Calico has a huge budget but terrible internal structure that has essentially created an internal valley of death—many good aging researchers on good salaries, and many good pharma guys, but no-one who is actually developing and translating the technologies to solve aging (i.e. by repairing the hallmarks of aging).
That sounds like the people in the 1970s that they thought they could cure cancer by the end of the decade if they declare war on it.
It’s not an apt comparison for at two reasons:
Scientists were nowhere near understanding cancer in mice let alone curing it in 1970. By contrast, with anti-aging technologies such as senolytics we can already delay cancer (which kills 80% of mice typically) and extend healthy lifespan 30%.
Solving cancer is a potentially harder than slowing aging, since it involves intervening in the process further downstream i.e. when more damage has accumulated, rather than nipping it in the bud.
If you want further evidence, consider that the original paper, The Hallmarks of Aging (2013) published in the journal Cell is the most highly cited academic paper in the entire field—with over 6800+ citations. Although it was Aubrey de Grey who first conceived of the Hallmarks (which he called the ‘7 deadly SENS’ and categorised them slightly differently in his 2007 book, Ending Aging) it has now become the framework used by researchers in the field, and even included in academic courses—such as the lectures I was invited to give to clinical neuroscience students here at Oxford University about aging and neurodegeneration.
SENS and Hallmarks shouldn’t be mixed as was done here and in the OP; although both sometimes overlap, they’re separate and distinct. Aubrey de Grey was the first to categorize aging damage and strategies to repair that damage (SENS) back in 2002 and published Ending Aging in 2007 to further popularize it. But he didn’t publish Hallmarks, and Hallmarks doesn’t always overlap with SENS (e.g., no cure for cancer, ignores crosslinks). Hallmarks also advocates lots of messing-with-metabolism (gerontology rather than the engineering/maintenance/damage repair approach), which is a big no-no from the SENS perspective. And while Hallmarks is popular in academia, SENS is not, unfortunately. It all boils down to this: the SENS approach has a decent chance of reaching LEV in the not-too-distant future, whereas Hallmarks doesn’t and never claimed to.
(1) Charity recommendations
I would recommend donating to SENS Research Foundation or Lifespan.io.
SENS has funded a lot of really great research in the field, which you can view here.
Lifespan is involved in advocacy, and have been successful in hosting conferences and providing a platform for information sharing in the field. They have also crowdfunded some research.
Both the research and advocacy components are crucial for helping to expand the longevity field.
(2) Complexity of aging
Yes, the causes of aging are complicated—that is, how the damage accumulates—is complicated. But treating aging doesn’t actually require understanding how the damage accrues, using the SENS (strategies for engineering negligible senescence) approach. It only requires how to ameliorate the various types of damage (hallmarks of aging).
Bear in mind that overwhelming evidence in the past 20 years has suggested that all aging-related processes are, looking upstream, a result of the hallmarks of aging and that there is no other cellular phenomenon besides these 7-10 processes (depending on how they are classified) responsible for the aging process that cannot be reduced to them. In the past 20 years, no new hallmarks have been discovered and researchers are fairly confident that these are the only hallmarks there are to discover.
Here’s Aubrey de Grey’s explanation of the SENS approach:
“The basic point we’re making there is to contrast the regenerative approach with the more traditional idea of trying to make metabolism create molecular and cellular damage more slowly. In order to do the latter, we would need to understand our biology massively better than we do at present, so as to avoid creating unforeseen side-effects. By contrast, with the regenerative approach we don’t need to know much about how damage comes about: it’s enough just to characterize the damage itself, so as to figure out ways to repair it. We’re effectively sidestepping our ignorance of metabolism. Rejuvenation biotechnologies are simply regenerative therapies that pre-empt the diseases and disabilities of old age. They consist of molecular, cellular or whole-organ interventions that restore the structure of the target to something like how it was in early adulthood.”
Is there any polling about how many of the anti-aging researchers believe this thesis?
To the best of my knowledge, there has not been polling of this question to anti-aging researchers (geroscientists) specifically.
However, if you watch lectures by anti-aging researchers, and the major conferences such as ARDD, EARD, CSHL Mechanisms of Aging and so on, most of them seem to use this paradigm when discussing aging and many even have a slide on the hallmarks of aging. All of the big names such as David Sinclair, Brian Kennedy, Lynne Cox, Judith Campisi, Alex Zhavarankov, and many others all mention the hallmarks of aging.
If you want further evidence, consider that the original paper, The Hallmarks of Aging (2013) published in the journal Cell is the most highly cited academic paper in the entire field—with over 6800+ citations. Although it was Aubrey de Grey who first conceived of the Hallmarks (which he called the ‘7 deadly SENS’ and categorised them slightly differently in his 2007 book, Ending Aging) it has now become the framework used by researchers in the field, and even included in academic courses—such as the lectures I was invited to give to clinical neuroscience students here at Oxford University about aging and neurodegeneration.
So it’s fair to say that it is now the consensus that the hallmarks of aging is the predominant view of the field, even though this was not the case 10-15 years ago when other theories of aging such as the free radical theory of aging held more weight.
If you are in a position to be invited to such talks, it might be worthwhile to put information about your identity into your post. Maybe as part of a epistemic status tag on the top.
The thing that’s very unclear to me is why SENS has so little funding if that’s framework is now consensus.
It seems like while the metformin trial study seems like good value for money in contrast to typical NIH funding, funding it with a decade worth of SENS funds wouldn’t be good value for money if SENS works. Why doesn’t SENS succeed at having a 8 or 9 figure budget? Which arguments are keeping the billionaire money from funding it stronger while the metformin trial study did get it’s money?
I guess one reason is that billionaires don’t have time to do their research in detail, to see for themselves whether de Grey and Sens are worthy, but rely on reputation and opinions of popular names in the field. And the reputation of SENS seems to have suffered a bit initially, when many scientists found their proposals for rejuvenation too bold or futuristic https://en.wikipedia.org/wiki/Aubrey_de_Grey#Criticism
SENS Research Foundation aren’t the only source of funding for research into the hallmarks of aging. The research into the hallmarks of aging labs at NUS, the Buck Institute, Oxford, Harvard and many other institutions is largely funded through the traditional route of national medical research councils. SENS Research Foundation funds some of the research, but by no means most of it. That said, they have a good track record of selecting some of the most important projects to fund despite a small budget of $5-10 million. For a point of comparison, the National Institute of Aging which as a $3 billion budget allocates around $100 million to geroscience.
Because they choose the most neglected (long-term/difficult/high-risk high-reward) projects within the Hallmark framework (I talked extensively about this in my posts if you want to take a peek).
Why wouldn’t billionaires (outside of Thiel and Greeves) that donate money for improving health outcomes want to fund long-term/difficult/high-risk high-reward projects?
Do you know whether SENS request a grant from OpenPhil?
Yes, and there are some signs that more billionaires (at least, the progressive-minded ones) are taking this seriously. For example, Elon Musk in an interview 3 weeks ago (timestamp: 24:03) mentioned the feasibility of ‘stop[ping] aging’ when asked about the biggest threats to the future of humanity, for the first time on the public record.
Two scientific advisors from OpenPhil conducted a ‘medium’ depth investigation into anti-aging in 2017 and seemed to understand the problem, though were less optimistic about anti-aging timelines, and funding this research area. They made the following forecast:
However, I would strongly disagree with this timeline, based on my knowledge of the field, today. I would go so far as to say that some combination of therapies available today—including metformin, senolytics, blood plasma exchange and epigenetic reprogramming—could already extend lifespan 25 years (compared to not taking the therapies) if personalised and multi-omics-biomarker-optimised. It’s just that we need more research to know how, when, where and how much of these therapies are required for each individual. With another 46 years of research in a field that is already expanding, I have no doubt that 25-year lifespan extension will be available by 2067.
They also summarised what a few of the anti-aging approaches (senolytics, stem cell therapies) but neglected many of the most promising approaches such as plasma exchange, partial epigenetic reprogramming, and mTOR inhibition.
They also made a big mistake, in my opinion, by overevaluating the amount of funding that geroscience (i.e. research that is relevant to the development of anti-aging therapies) receives:
It is clear to almost everyone working in the field that the amount of funding going towards geroscience—i.e. targeting aging therapeutically—is drastically lower than that of age-related diseases—which employ completely different research methods and experimental protocols (i.e. do not perform lifespan studies with geroprotective interventions prior to disease onset). A list of most of the researchers working in the field is here (last updated April 2020) though I don’t think OpenPhil cared to look deeply enough into the field to recognise the lack of researchers and funding for geoscience in particular.
There are other flaws in their analysis. For example, they mentioned the large funding that Google-backed Calico receives, here:
However, as Aubrey de Grey explains in this interview, Calico—despite having a huge budget—have a poor organisational structure that has so far precluded any meaningful research advances in the field.
As Aubrey de Grey puts it in the interview (from ~1:14:00 onwards):
So overall, I believe OpenPhil are inaccurate in their assessment of the geroscience field based on their ‘medium’ depth investigation into it. There are numerous other examples of statements in their write-up that demonstrate a poor or incomplete knowledge of the state of the field—both scientifically and economically. I can go into these if you like, and I’ll probably write up a post about this in the future.
Youtube allows you to link to specific timestamps when you click on the share button.
I think there are two separate issues. One is about aging being taking seriously and the other is about SENS being taken seriously.
I think you have the wrong link. In any case Aubrey de Grey basically here that hiring credentialed people is not enough to get results but that if he would organize the research it would produce better results. While that might be true it’s hard to assess.
That sounds like the people in the 1970s that they thought they could cure cancer by the end of the decade if they declare war on it.
Thanks for the tip.
Sorry, here is the link. It’s not that hard to assess, given he has many informal chats with people affiliated with Calico. His point is that Calico has a huge budget but terrible internal structure that has essentially created an internal valley of death—many good aging researchers on good salaries, and many good pharma guys, but no-one who is actually developing and translating the technologies to solve aging (i.e. by repairing the hallmarks of aging).
It’s not an apt comparison for at two reasons:
Scientists were nowhere near understanding cancer in mice let alone curing it in 1970. By contrast, with anti-aging technologies such as senolytics we can already delay cancer (which kills 80% of mice typically) and extend healthy lifespan 30%.
Solving cancer is a potentially harder than slowing aging, since it involves intervening in the process further downstream i.e. when more damage has accumulated, rather than nipping it in the bud.
I dont’t know actually (for both questions). And I’m not sure how many billionaires like this there are.
SENS and Hallmarks shouldn’t be mixed as was done here and in the OP; although both sometimes overlap, they’re separate and distinct. Aubrey de Grey was the first to categorize aging damage and strategies to repair that damage (SENS) back in 2002 and published Ending Aging in 2007 to further popularize it. But he didn’t publish Hallmarks, and Hallmarks doesn’t always overlap with SENS (e.g., no cure for cancer, ignores crosslinks). Hallmarks also advocates lots of messing-with-metabolism (gerontology rather than the engineering/maintenance/damage repair approach), which is a big no-no from the SENS perspective. And while Hallmarks is popular in academia, SENS is not, unfortunately. It all boils down to this: the SENS approach has a decent chance of reaching LEV in the not-too-distant future, whereas Hallmarks doesn’t and never claimed to.