This page is a summary of the paper "Paper summary: The hoverfly and the wasp: A critique of the hallmarks of aging as a paradigm" [1][2], and my thoughts. The paper is a critique for famous paper "The hallmarks of aging" [3].
The "hoverfly and the wasp" means that the paper "The hallmarks of aging" mimics like "The hallmarks of cancer" to fool people. The paper says "The hallmarks of aging" is a mimicry of paradigm. But actually the content of this paper is not related to "hoverfly" and "wasp" at all.
This resembles an exercise in mimicry: as the hoverfly mimics the wasp to fool predators into believing that it has a sting, the hallmarks of aging puts on a resemblance to the hallmarks of cancer, to give the impression of a paradigm where one does not exist.
I don't like analogy in paper. I don't find any benefit of that. It's just make me hard to understand it. There is another analogy in the "Concluding remarks" section. I think analogy is an enemy of objectivity.
In this context, the scheme is akin to a folding screen bearing a hallmarks of aging diagram that blocks the view of the true state of undress of the field. Shivering behind the screen is the ailing damage maintenance paradigm.
Introduction The paper cites "The Structure of Scientific Revolutions" - Thomas Kuhn, and introduces a traditional paradigm before "The hallmarks of aging".
An emerging paradigmatic crisis in the aging field
- Arrival of the hallmarks of aging
A number of companies (e.g., Life Biosciences) have been set up to focus specifically on the hallmarks of aging.
- Measuring the hallmarks of aging against the hallmarks of cancer
- (i) Cellular damage is assumed (as is traditional) to be the main causal common denominator of aging, but this is not certain.
- (ii) The list of hallmarks is somewhat arbitrary.
- Introduction of similar less cited paper "The Seven Pillars of Aging" [4] but not mimicing "The hallmarks of cancer".
Biogerontology is in many ways still a relatively immature field, certainly far less mature than oncology.
- (iii) Support for definition of hallmarks as primary vs secondary causes is sometimes lacking.
- The "deregulated nutrient" can be a primary hallmarks.
Identification of wild-type insulin/IGF-1/mTOR signaling as a cause of multiple diseases of aging and shorter lifespan in animal models. Here wild-type gene action and signaling is clearly identified as a primary cause of aging, not the deregulation of these pathways, and certainly not deregulation resulting from damage.
- (iv) Claims about how upstream causes give rise to downstream outcomes are often unproven.
- (v) How the secondary/tertiary causes give rise to aging is unclear
An alternative view is that interventions that markedly extend lifespan do not do so by slowing the overall aging process, but rather by inhibiting determinants of multiple senescent pathologies - or etiologies of multimorbidity. Potential examples here are mTOR hyper-activity specified by wild-type gene function , and senescent cell accumulation.
- The hoverfly and the wasp: pseudo-hallmarks and pseudo-paradigm
- Saying "The hallmarks of aging" mimics!
- What might an operative paradigm look like?
First, the main classes of primary cause of pathology in earlier life: mechanical damage (injury; c.f. mechanical senescence), molecular damage (including inherited and acquired mutations) and infectious pathogens. Second, the far less well understood classes of mechanism by which the wild-type genome determines aging rate.
- Suggesting an alternative paradigm templates: multiple primary mechanisms template.
- DNA damage is an important driver of cancer in mammals, but not in aging in C. elegans.
- Concluding remarks
In fact, the traditional framework of mechanistic theories that has guided biogerontology for 30 years is in a state of paradigmatic crisis and transition. In this context, the scheme is akin to a folding screen bearing a hallmarks of aging diagram that blocks the view of the true state of undress of the field. Shivering behind the screen is the ailing damage maintenance paradigm.
