Integrating evolutionary theory into a framework for the mechanistic evaluation of candidate anti-aging interventions.

Abstract

Despite decades of research into the molecular hallmarks of aging, geroscience lacks a unifying framework that both coherently integrates evolutionary accounts of aging and is directly useful for intervention assessment. Here, we propose the 'Aging Onion', a layered, two-axis framework developed to help interpret the diversity of phenotypes associated with aging, and informed by the mechanistic emphases foregrounded by the Disposable Soma and Hyperfunction traditions. In this framework, persistent activity of growth and developmental programmes, alongside insufficient somatic maintenance, define two broad biological axes through which we attempt to interpret age-related degeneration, and intervention responses. To examine the utility of this framework, we focus on nutrient sensing as an initial benchmark domain. Within this space, caloric restriction is a conserved reference intervention, while rapamycin provides a narrower pharmacological comparator acting primarily through TOR-centred signalling. We ask whether the proposed axes of the Aging Onion can help ground the mechanistic divergence between these interventions in aging-relevant biology and thereby interpret their differing efficacies. We conclude by outlining future directions for testing whether this framework can be operationalised in broader intervention assessment, and for determining whether its layered logic generalises beyond nutrient sensing to other domains of aging biology, including population-genetics approaches.