preprints.org > medicine and pharmacology > other > doi: 10.20944/preprints202409.1180.v1 (registering DOI)

Preprint Hypothesis Version 1 This version is not peer-reviewed

Version 1 : Received: 15 September 2024 / Approved: 16 September 2024 / Online: 16 September 2024 (10:15:07 CEST)

Late-life diseases result from the poorly understood process of senescence (aging), that is largely genetically determined. According to a recently proposed evolutionary physiology-based account, the multifactorial model, senescence is largely caused by evolved but non-adaptive programmatic mechanisms specified by the wild-type (i.e. normal) genome. These act together with disruptions to wild-type function (due e.g. to infectious pathogens, mechanical injury and malnutrition) in a variety of combinations to generate diverse late-life diseases. Here the utility of this model is explored by testing its capacity to provide an account of one complex, late-life disease, osteoarthritis (OA), and a framework for understanding OA etiology suggested. In this framework, the core OA disease mechanism is a futile endochondral ossification quasi-program (non-adaptive developmental program), in which hypertrophic articular chondrocytes alter joint architecture. Programmatic changes prime chondrocytes for quasi-program activation, which can be triggered by secondary causes of OA (e.g. joint mechanical injury). A suggested evolutionary cause of this priming, involving antagonistic pleiotropy, is selection to maximize early life tissue repair benefits at the expense of late-life programmatic costs.

antagonistic pleiotropy; chondrocyte; evolutionary medicine; hyperfunction; osteoarthritis; programmatic theory

Medicine and Pharmacology, Other

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