Critiquing the Hallmarks of Aging

The biggest problem I see with the Hallmarks of Aging paper is not really the fault of its authors, but rather that a sizable part of the research community now takes that list of aging associated mechanisms as a guide to points of intervention in aging. Unlike the SENS view of aging, a list of mechanisms in aging that preceded the Hallmarks paper by more than a decade, the Hallmarks were not established to be a list of root causes of aging, and were never intended to be taken as such.

In the case of SENS, wherein a great deal of thought has gone into identifying mechanisms that are root causes of aging, one can proceed logically from the mechanisms to building treatments that target those mechanisms. In the case of the Hallmarks, that a specific hallmark exists does not in and of itself justify a strong focus on targeting it; it can be a downstream consequence of the underlying causes of aging, and thus targeting it will not yield meaningful results.

As the main cause of disease and death in the modern world, senescence (i.e. aging; not to be confused with replicative or cellular senescence) is one of the major biological and medical challenges of the 21st century. It would therefore be invaluable to understand the central biological mechanisms of senescence and how they give rise to late-life disease, including cardiovascular disease, many forms of cancer, chronic obstructive pulmonary disease (COPD), dementia, and many other maladies.

With the goal of representing common denominators of aging in different organisms, in 2013 researchers described nine hallmarks of aging. Since then, this representation has become a major reference point for the biogerontology field. The template for the hallmarks of aging account originated from landmark papers defining first six and later ten hallmarks of cancer. Here we assess the strengths and weaknesses of the hallmarks of aging account.

As a checklist of diverse major foci of current aging research, the hallmarks of aging has provided a useful shared overview for biogerontology during a time of transition in the field. It also seems useful in applied biogerontology, to identify interventions (e.g. drugs) that impact multiple symptomatic features of aging. However, while the hallmarks of cancer provide a paradigmatic account of the causes of cancer with profound explanatory power, the hallmarks of aging do not.

A worry is that as a non-paradigm the hallmarks of aging have obscured the urgent need to define a genuine paradigm, one that can provide a useful basis for understanding the mechanistic causes of the diverse aging pathologies. We argue that biogerontology must look and move beyond the hallmarks to understand the process of aging.


Mainstream medicine has always been behind the curve on this stuff.

Posted by: Abelard Lindsey at May 20th, 2021 9:36 AM

"A worry is that as a non-paradigm the hallmarks of aging have obscured the urgent need to define a genuine paradigm, one that can provide a useful basis for understanding the mechanistic causes of the diverse aging pathologies."

I never saw an explanation by Pedro de Magalhaes of why don't he think that SENS is such a basis, after all these years (and he knows about SENS almost from the beginning).

Posted by: Antonio at May 20th, 2021 1:24 PM

Hello, I have some questions about this:

-What is your opinion about David's Sinclair theory? As I understand, he says there is only one cause that causes all the others, and that is epigenome instability.

-Are there more teories about the causes of aging? I know these 3: Aubrey de Grey, Hallmarks and David Sinclair

-Are there any debate among Aubrey and the people of Hallmarks, or Aubrey an Sinclair, or Hallmarks and Sinclair? If not, why? And what can we do to make it happen? I think that would push the field of antiaging forward



Posted by: Josep at May 21st, 2021 4:51 AM

@Josep: I think that Sinclair sees epigenetic patterns as a good point of intervention, not a cause of aging in the same way the Russian programmaged aging folk see it. His materials point to cycles of DNA damage and repair as a major cause of systemic and characteristic epigenetic change. Sinclair is a relentless publicist, and one only has to look at his history with resveratrol and sirtuins to see that one shouldn't take anything he says seriously unless it is in a scientific paper.

Posted by: Reason at May 21st, 2021 7:19 AM

-Who is the Russian folk?
-What about the other questions?

Thanks for answering


Posted by: Josep at May 21st, 2021 7:30 AM

" why don't he think that SENS is such a basis" - if you want to understand, you need to look at results from clinical studies done in humans, not endless theoretical papers published by sens - sens preached "removed the damage" idea, which was running into issues with beta amyloid clearance (= no results). then unity failure to prove that removing senescent cells are better than a steroid treatment, clearly indicated how "fundamental" sens's ideas are ... therefore a lot of "credibility" for sens ... also some senescent cells are actually beneficial ... so just use this info and you will understand "why".

Posted by: sw at May 21st, 2021 11:10 AM

@May none of pre-cancer ("senescent" cells) are beneficial. It's just evolution used their signal in fetus develpment and skin repair as signal to begin creating skin. Regenerating telomeres is uncomaparably better way to avoid them in the first place, but when they are in the body they block highly efficiently all telomerase expression, so cancer cells must express it >10 times more than level needed to maintain their length just to overcome this switching off effect of senescent cells.

Posted by: SilverSeeker at May 22nd, 2021 3:21 AM
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