"The physician is constantly referring to the biologist for a scientific basis for geriatrics, and finding that it is not there" Alex Comfort1.

Abstract

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 I explore the utility of this model by testing its capacity to provide an account of one complex, late-life disease, osteoarthritis (OA), and suggest a framework for understanding OA etiology. In this cartilage-focused framework, a core OA disease mechanism is a futile (non-adaptive) developmental program of endochondral ossification, in which hypertrophic articular cartilage chondrocytes alter joint architecture. Programmatic changes prime chondrocytes for futile program activation, which can be triggered by secondary causes of OA (e.g. joint mechanical injury). I suggest that an 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.