There are extensive ongoing efforts to slow or even reverse human aging, such as with epigenetic cellular reprogramming, thymus rejuvenation or senolytics. In parallel, new and diverse metrics—known as biological clocks—have been discovered and shown to track the pace of aging in an individual and their organs, tissues and cells. These clocks have multiple potential use cases, including identifying people at high risk of disease, serving as a foundation for prevention or early detection, and determining whether lifestyle factors or an intervention can modulate the aging process. This review provides a critical appraisal of the progress that is being made with biological clocks and how they might ultimately help understand pathobiology, reduce the burden of disease and extend healthspan.
Across cultures, humans have long sought to extend lifespan and delay
aging. Once viewed as speculative, rejuvenation and longevity are now
mainstream scientific pursuits, enabled by converging advances in
molecular biology, genomics, high-throughput proteomics, single-cell
technologies and artificial intelligence (AI). Average human lifespan has
nearly doubled over the past century, but healthspan, the years lived in
good health, has not increased at the same rate. Consequently, more
people across the globe are with age-related cardiovascular disease,
cancer, dementia and frailty.
At the same time, aging research advanced to demonstrate that
aging is not a single, uniform process but a collection of overlapping
molecular and physiological changes that unfold, at different rates,
within an individual. One of the most important advances is the abil-
ity to use biological clocks to quantify the aging process at the whole
organism, organ and cellular levels. From the first epigenetic clocks
built on DNA methylation patterns to plasma proteomic clocks for
individual organs and cells, AI-based readouts of the retina and emerg–
ing multi-omic and electronic health record (EHR)-based metrics, the
field now possesses a sizeable toolkit for tracking how each person
ages. These research tools reveal nonlinear and asynchronous trajec-
tories of aging and functional decline, linking lifestyle and exposures
to molecular changes. They have the potential to identify individuals at
elevated risk for specific diseases years before symptoms, and to serve
as early endpoints for trials of geroprotective interventions. While
there are multiple caveats and a lack of readiness for use in medical
practice, molecular clocks lay the foundation for tracking the aging
process for people in the future.