Reporting on the Second Interventions in Aging Conference
This report captures the state of the research community in a nutshell: progress in the sense that ever more scientists are willing to make the treatment of aging the explicit goal of their research, but, unfortunately, there is still a long way to go in improving the nature of that research. It is still near entirely made up of projects that cannot possibly produce a robust and large impact on human life span. The only course of action likely to extend life by decades in the near future is implementation of the SENS vision for rejuvenation therapies - to repair the molecular damage that causes aging. Everything else on the table is some form of tinkering with the operation of metabolism in order to slightly slow down the accumulation of that damage, such as via capturing some of the calorie restriction response or boosting autophagy. In any machinery, repair is a vastly better strategy for improving function and extending working life span, and our biology is no exception.
In March 2017, the Second Interventions in Aging Conference was held in Cancun, Mexico. The meeting, similar to the earlier event in 2015, was focused on interventional strategies. One notable difference was that this year's meeting was much more directed toward potential interventions to target human aging. The field has been very successful over the last decade in identifying interventions that extend lifespan and healthspan in animal models such as yeast, flies, worms, mice and, to some extent, primates. However, the primary goal is to employ knowledge from basic aging research to develop novel medical strategies aimed at extending human healthspan. Aging is the biggest risk factor for a wide range of chronic diseases that, to date, medical strategies have treated as separate entities, and as they arise. Yet, aging is driven by a limited number of coordinated pathways that can be modulated, and evidence suggests that interventions delaying aging will protect against multiple age-related diseases simultaneously. Discoveries in basic aging research thus point towards a broad-spectrum, preventative, medical strategy for aging-related disease.
There were seven research topics each addressed thematically at the meeting. All were chosen because they embody different strategies to target human aging. Each session combined talks from Platform speakers with those chosen from submitted abstracts. The first and largest theme was targeted toward Organismal Aging, or understanding the intrinsic pathways that govern aging of the entire organism. The interesting aspect of these presentations is that they address strategies to modify aging that touch back to research from the early days of aging research while simultaneously pointing to novel strategies for future interventions: new mechanisms linking growth hormone signaling to aging; using mammalian models to re-evaluate the role of reactive oxygen species; new evidence for links between progeria and normal aging, interpreting these strategies in the context of possible interventions that may affect both normal and "premature" aging; linking NFκB signaling to sarcopenia, a major driver of frailty in aging; mechanisms linking calorie restriction to lifespan extension in primates; strategies to examine the impact of aging pathways in elderly human populations.
The second theme was focused on using Stem Cells to target aging, with exciting presentations on aging of epithelial stem cells in flies and mice, on links between metabolism, autophagy and aging in the hematopoietic system, and on how adult stem cells self-organize into functional configurations. The third theme, addressing Cellular Mechanisms of Longevity Assurance, focused on pathways suspected to modulate aging, including autophagy, mitochondrial function and aging with emphasis on the role of small mitochondrial peptides, and the hypoxia pathway. Theme 4 centered on Epigenetics, which is not only becoming a target for intervention in aging, but is rapidly becoming a leading candidate for providing biomarkers of biological age: mechanisms leading to transgenerational inheritance of epigenetic marks that impact lifespan; links between the epigenome and activation of somatic retrotransposons, and how this activation may drive senescence and aging; further promoting the epigenetic clock as a marker of accelerated and delayed aging.
Theme 5 was designed to take a Systems Aging viewpoint. Such a holistic understanding of the aging process is in a sense the ultimate goal of the research. Is it possible to understand such a complex process as aging not just one gene and pathway at a time but in totality? The final theme centered on Signaling and Metabolism, hitting the major metabolic pathways that are linked to aging and that can be targeted with interventional strategies. These include the mTOR pathway and rapalogs; dietary restriction and links through mTOR to regulation of mRNA splicing; NAD metabolism and sirtuins; mitochondrial roles in regulating aging and metabolism.
I can't help but think most of the research on aging, considering its complexity, is pathetic. Without SENS, I would have no hope. I think SENS circumvents the inherent complexity in a clever way, not being so stubborn or fixed about how to reach a certain outcome. I feel there's still a long road ahead of us, though.
I expect a fair number of them are also "healthspanners". Our goal is to increase healthy years not lifespan, such a broken rationale. Oh and look here we are:
"The field has been very successful over the last decade in identifying interventions that extend lifespan and healthspan in animal models such as yeast, flies, worms, mice and, to some extent, primates. However, the primary goal is to employ knowledge from basic aging research to develop novel medical strategies aimed at extending human healthspan."
*sigh* such a lack of vision. So they know we can increase lifespan and healthspan but the primary goal is healthspan, it's very sad actually that these researchers just dont get on the bus and admit that BOTH is the goal.
@Steve - there seems to be a lot of frustration that aging researchers won't lead public opinion into supporting aging research. But is it really their job? They are funded by cautious politicians. They naturally want to under promise and then over deliver to avoid disappointing their finders, which is why Aubrey and his 1000 year lifespan claim is such an annoyance.
If people did the things that benefited everyone in the medium term rather than themselves in the short term then the world might be a better place. It would also be weird, as those people wouldn't be rational humans.
Maybe it will be like self driving cars, which a decade and a half ago seemed impossible to the public, but now seem inevitable.
I know Jim and I and our team are working to change the situation. I think we are doing ok so far, its just annoying seeing healthspan touted as the holy grail. Still we will keep on pushing and wash away these ideas and get everyone on the bus sooner or later!
Steve, if you follow a SENS model approach to regeneration and repair, there is likely no way to achieve healthspan improvements without also improving lifespan (at least median if not maximum). But both academics and companies have to play the healthspan card for political reasons. Amongst our SENS community, we can be fairly confident that most of us use healthspan in the so-called "dog whistle" version of the word - we know we are talking lifespan.
@jim: It has been argued that it is their job, though there are other groups that might have as a large an impact should they get organized:
https://www.fightaging.org/archives/2004/06/the-curious-case-of-the-catatonic-biogerontologists/
I have read the fight aging blog for a while, and I have filmed many of the major scientists in the
field, including Guarantee, Sinclair, Aubrey, Kennedy, Kenyon, Austad, the Conboys, to name some. I know what they say and don't say. Here is my point: having delved into the subject
for 10 years, it is becoming clear - that, for instance, in the case of stem cells and Conboys' work - stem cells don't age like normal cells - they can be made to act young again, given the
proper environment. THE BODY WILL DO THE HEAVY LIFTING. A recent paper from Salk hints
at that again, epigenetic signally marks can be undone, by the body. If you remove (or back up) certain elements of damage, things that are going wrong might stop going wrong or even reverse themselves. The body will make the thousands of choices needed to do the job.
I believe this applies to NAD (and beta lapachone) and mtor pathway vis a vis rebooting the immune system.
I won't go on; suffice to say that tweaking key pathways may itself help the body reverse aging.
It is not clear that only damage removal can accomplish this. I am personally optimistic. A real issue is the PR game, public perception and its effect on funding. I sometimes drink with scientists off the record and I think this represents some of the thinking. To me this blog is at times a bit shortsighted as well, though a good resource for papers.
The mainstream research community, as always, is frustrating. We can't expect much from them, we must somehow fund the useful research ourselves, with our money and our advocacy to possible crowdfunders.
If these scientists were mechanics they'd be spending billions of dollars studying how engine oil quality breaks down over time to see whether they could adjust the metabolism of the car to make it run slightly longer on sludge before it broke down. Meanwhile, Aubrey de Grey would be standing to the side saying "Just change the damn oil"
I love this analogy, Link !
@Gary I know some researchers use healthspan as a "dog whistle" and yes I follow a repair approach to aging ala SENS ala Hallmarks of aging style.
@Link that is a great analogy.