Biomarkers

A biomarker of aging is a biological parameter of an organism that, either alone or in some multivariate composite, will in the absence of disease better predict functional capability at a late age than will chronological age. ^[1] Aging biomarkers are a combination of biological parameters used to assess age-related changes, track the physiological aging process, and predict the transition into a pathological status. ^[2] The current lack of standards and consensus on the properties of a reliable aging biomarker hinders their further development and validation for clinical applications. ^[3]

Aging biomarkers have been developed for cellular, organ, and organismal levels of aging and comprise six pillars: physiological characteristics, medical imaging, histological features, cellular alterations, molecular changes, and secretory factors. ^[2] Biomarkers of ageing based on DNA methylation data have enabled accurate age estimates for any tissue across the entire life course, and these epigenetic clocks link developmental and maintenance processes to biological ageing. ^[4] Biomarkers centered on function, resilience, and frailty are available at present, with proven predictive value for morbidity and mortality, whereas molecular parameters hold promise for the future. ^[5]

With the rapid expansion of aging biology research, the identification and evaluation of longevity interventions in humans have become key goals, and biomarkers of aging are critically important tools for achieving these objectives over realistic time frames. ^[3] Omic-based biomarkers of aging could predict aging-related outcomes and serve as surrogate endpoints for the evaluation of interventions promoting healthy aging and longevity. ^[6] Identifying biomarkers of age that classify people as biologically older or younger than their chronological age is becoming of paramount importance, as such people are at higher or lower risk for many age-associated diseases. ^[7]

A 3-round Delphi expert consensus identified 14 potential biomarkers of aging for use as outcome measures in intervention studies, spanning physiological, inflammatory, functional, and epigenetic domains. ^[8] The consensus biomarkers include physiological markers such as insulin-like growth factor 1, inflammatory markers such as high-sensitivity C-reactive protein and interleukin-6, functional measures such as muscle strength, hand grip strength, gait speed and blood pressure, and epigenetic clocks based on DNA methylation. ^[8] No consensus exists on how biomarkers of aging should be validated before their translation to the clinic, and systematic validation could accelerate their use in gerotherapeutic clinical trials. ^[6] Clinical translation of biomarkers of aging remains limited, and key recommendations include linking them to clinically actionable insights, improving affordability and availability, and validating biomarkers that are robust and responsive at the level of individuals.