Ageing was never a singular problem in biology: implications for mechanisms, measurements and interventions.

Abstract

Biological ageing is often approached through its underlying mechanisms and their therapeutic potential. Yet age-related decline arises from multiple processes shaped by evolutionary constraints and finite investment in somatic maintenance. Coupling among these processes is heterogeneous: some are tightly linked through shared signalling networks, others are indirectly related and some retain substantial autonomy. Interventions that modulate biomarkers of biological age or individual hallmarks typically produce partial, tissue-selective effects rather than uniform reversal of ageing in humans. This pattern is more consistent with a distributed network of partially independent processes with key nodes of regulatory integration than with a single upstream mechanism. Because molecular, cellular, tissue and organismal levels retain partial autonomy, human ageing can be viewed as a multilevel phenomenon. Geroscience may therefore advance by mapping this network and identifying interventions that target central regulatory hubs and affect multiple downstream processes, thereby preserving function, extending healthspan and reducing the burden of ageing.