Thread by @PtitPhiSciences

New paper on the evolution of #aging out! The first systematic review of the presence of the various known mechanisms of aging across the tree of life, the goal being to provide #geroscience and #biogerontology with a more solid framework. 1/10
frontiersin.org/articles/10.33…

The evolution of aging has been addressed at a general or theoretical level by major scientists, but no one had tried yet to address the basic question of the order of apparition of the various mechanisms of aging during evolution, with a focus on human aging. 2/10

The paper is based on a common hypothesis on the order of clades from cellular organisms to bilaterians. It also starts with the well-known hallmarks of aging but proposes a more precise decomposition into 20 specific hallmarks of aging (instead of the 9 generic hallmarks). 3/10

The method is: investigate the presence of these mechanisms of mammalian aging we know in the earliest organisms of a given clade -e.g, is there aging by genetic mutations, epigenetic alterations, loss of proteostasis, etc., in E. coli, S. cerevisiae, choanoflagellates, etc. 4/10

The result is surprising. For instance, there is strong evidence that the oldest mechanism of aging is the loss of proteostasis, and it is very likely that aging by accumulation of mutations is the most recent mechanism of aging (present only in bilaterians). See figure. 5/10

A major result of the paper is also that the critical mechanisms of aging in senescent multicellular organisms are likely not to originate in the aging of individual cells, but rather, in the organization of cells into an organism. 6/10

The paper thus distinguishes between unicellular aging (typically, loss of proteostasis or loss of mitochondrial integrity) and metacellular aging (typically, transcriptional alterations or inflammation). 7/10

Strikingly enough, the evidence is rather consistent that early multicellular organisms were not senescent, because they had solved the problem of the degradation of individual cells (by ways of renewal of tissues that are few and simple in structure). 8/10

Multicellular senescence is likely to have appeared with increasing complexity. 9/10

A general suggestion for strategies in #geroscience is that interventions targeting the aging of individual cells are likely to have a less important postponing effect that interventions targeting the alteration of metacellular aging 10/10