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Paper summary: The hoverfly and the wasp: A critique of the hallmarks of aging as a paradigm

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.

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