The stress of aging

Although the evolutionary theories of aging are quite well established, our knowledge about how we age isstill very limited. The abundance and heterogeneity of available mechanistic theories of aging implicitly suggestthat this phenomenon is overly complex and unlikely to be explained by a single pathway. Moreover, although aging remains a unique process, it is characterized by heterogeneous manifestations, not only determininginter-individual variations, but even intra-individual diversities. Such heterogeneity renders the innernature of the aging process of difficult evaluation in older persons due to the potential biases introduced bymultiple age-related social, biological, and clinical factors (and responsible for the evidence-based issue ingeriatrics). Moving from the difficulties in translating anti-aging preclinical interventions into clinical trials, an alternative approach is illustrated. We encourage moving to a holistic evaluation of aging by adopting specificand consequent modifications in the design and conduction of clinical research. Such approach is today commonlyapplied in the clinical setting where the complexity of older patients often requires multidimensional interventionsto adequately target the geriatric syndromes. Consistently, interventions targeting the aging processmay result ineffective if too focused on a single underlying causalmechanism and/or failing to capture the complexityof the phenomenon. In this context, frailty (a geriatric syndrome characterized by age-related declinesoccurring acrossmultiple physiologic systems) may indeed represent a clinically relevant threshold throughoutthe continuum of the aging process and a promising benchmark to test multidomain interventions againstage-related conditions.