An international team of scientists has unveiled a new biological age estimator—a blood-based “epigenetic clock” that measures how well an individual is ageing rather than merely indicating their chronological age. This innovative metric, known as the Intrinsic Capacity Clock (or IC Clock), shifts the focus from chronological age to functional age, assessing a constellation of six vital domains that together constitute what the World Health Organization (WHO) refers to as intrinsic capacity (IC): mobility, cognition, mental health, sensory function (vision and hearing), and vitality, particularly about nutrition.
As outlined in a recent publication in Nature Aging, the IC Clock represents a significant advance in geroscience and healthy longevity. Rather than concentrating on age as a linear trajectory toward decline, this tool emphasises the preservation of function—something older adults consistently rank as more important than survival or disease avoidance. “Maintaining function during the ageing process matters to older adults,” notes Dr David Furman, PhD, the study’s senior author and Associate Professor at the Buck Institute, where he directs the Bioinformatics and Data Science Core. “Function should inform medical care instead of focusing on getting patients to some disease-free state.” Initially proposed by WHO, the concept of intrinsic capacity was formally recognised in 2022 in the International Classification of Diseases (ICD-11), marking a conceptual shift in how ageing-related decline is clinically identified and potentially treated.
The IC Clock is the result of a transatlantic collaboration between researchers at the Buck Institute for Research on Aging in California and the Hospital-University Institute HealthAge in Toulouse, France, in conjunction with the French research organisation INSERM and the Université de Montpellier. This partnership reflects a growing convergence of North American and European efforts to develop tools for enhancing a healthy lifespan. The foundation of the IC Clock lies in data from the INSPIRE-T cohort—a ten-year longitudinal study involving 1,000 participants aged between 20 and 102 years from the region around Toulouse. Over the first four years of data collection, researchers captured extensive information on each individual’s physical and cognitive function, lifestyle, and biological samples, including blood, saliva, urine, and dental plaque, which were collected annually.
What sets the IC Clock apart from earlier models is its basis in DNA methylation—chemical modifications that serve as molecular indicators of gene expression patterns associated with ageing. The research team demonstrated its superior predictive ability by training the IC Clock model on the INSPIRE-T dataset and validating it using data from the long-standing Framingham Heart Study in Massachusetts. Specifically, the IC Clock outperformed first- and second-generation epigenetic clocks in forecasting overall mortality. According to Furman, it is the only ageing clock that currently integrates all known hallmarks of ageing. Moreover, individuals with higher IC Clock scores exhibited better immune performance, lower markers of inflammation, and healthier behaviours, suggesting that this new measure captures core aspects of biological resilience and systemic integrity.
Crucially, the IC Clock is designed to be practical and scalable. Work is underway to develop a dried-blood spot version of the tool, which would allow for assessments without the need for invasive clinical procedures—particularly advantageous in low- and middle-income countries where healthcare infrastructure is often limited. “If we can offer a scalable, affordable molecular-level tool to assess functional decline,” Furman explained, “the IC Clock could help clinicians, researchers, and policymakers better identify at-risk individuals and tailor interventions that promote a longer, healthier life.” By moving beyond organ-specific diagnostics and toward a unified index of bodily function, the IC Clock could transform preventative care and the global discourse on ageing.
Despite the WHO’s recognition of declining intrinsic capacity as a clinical condition, regulatory frameworks in the United States—most notably the Food and Drug Administration (FDA)—have yet to catch up. The classification of ageing as a disease remains controversial, posing a significant barrier to the approval of interventions targeting ageing-related decline. Furman believes that the IC Clock may help resolve this impasse. “We hope the IC Clock will ultimately enable the FDA to approve treatments that would improve health and function in older adults,” he said, suggesting the clock could become a regulatory anchor for future geroprotective therapies.
Looking ahead, the IC Clock will be deployed in the high-profile XPRIZE Healthspan competition—a global challenge backed by $101 million in funding over seven years, aimed at revolutionising how ageing is managed and mitigated. The Buck-Toulouse consortium has already been named a semifinalist in this ambitious effort, which seeks to identify interventions capable of reversing 10 to 20 years of biological ageing in core domains, such as muscle strength, cognitive capacity, and immune function, within a single year, among adults aged 50 to 80. Their proposed hybrid intervention combines daily supplementation with a ketone ester and a personalised, non-pharmacological protocol called ICOPE-INTENSE. This latter regimen integrates tailored components of exercise, cognitive stimulation, dietary optimisation, and social support—all designed to enhance the pillars of intrinsic capacity. The IC Clock will be the primary biomarker throughout the study to monitor and quantify participants’ functional response to the intervention.
The IC Clock’s development marks a compelling shift in how we approach ageing—not as an inevitable march toward frailty and disease, but as a modifiable state that can be measured, monitored, and potentially improved. In highlighting the biological substrates of functional health and offering a scientifically validated tool to assess them, the IC Clock has the potential to inform clinical decisions, guide public health initiatives, and shape regulatory policies on a global scale. Whether it will ultimately usher in a new era of longevity-focused medicine depends on further validation and scalability and on societal willingness to redefine what it means to age well.
More information: David Furman et al, A blood-based epigenetic clock for intrinsic capacity predicts mortality and is associated with clinical, immunological and lifestyle factors, Nature Aging. DOI: 10.1038/s43587-025-00883-5
Journal information: Nature Aging Provided by Buck Institute for Research on Aging
