A gerophysiology perspective on healthy ageing
Résumé
Improvements in public health and health care have resulted in significant increases in lifespan globally, but also to a significant increase in chronic disease prevalence. This has led to focus on healthy aging bringing a shift from a pathology centered to an intrinsic capacity and function centered view. In parallel, the emerging field of geroscience has promoted the exploration of the biomolecular drivers of ageing towards a transverse vision by proposing an integrated set of molecular hallmarks. In this review, we propose to take a step further in this direction, highlighting a gerophysiological perspective that considers the notion of homeostasis/allostasis to robustness/fragility respectively. While robustness is associated with homeostasis achieved by an optimal structure/function relationship in all organs, successive repair processes occurring after daily injuries and infections result in accumulation of scar healing leading to progressive tissue degeneration, allostasis and frailty. Considering biological aging as the accumulation of scarring at the level of the whole organism emphasizes three body transverse and shared key elements– mesenchymal stroma cells/immunity/metabolism i.e. SIM and play down parenchyma cells. This SIM tryptich drives tissue and organ fate and appears as a shared and common reservoir to regulate the age-related evolution of body functions. It provides the basis of a gerophysiology perspective, possibly representing a better way to decipher healthy ageing, not only by defining a composite biomarker(s) but also by developing new preventive/curative strategies.
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