A groundbreaking advancement in the science of aging has emerged from an international collaboration of researchers who have developed a sophisticated biological age “clock” known as the Intrinsic Capacity (IC) Clock. Unlike conventional aging clocks that primarily estimate chronological or organ-specific age, the IC Clock innovatively measures the overall functional capacity involved in the aging process. This novel clock, recently detailed in a study published in Nature Aging, focuses on intrinsic capacity—the aggregate of six critical domains that define healthy aging: mobility, cognition, mental health, vision, hearing, and nutrition/vitality. This comprehensive approach transcends the traditional emphasis on disease states to reflect how well an individual ages functionally, thus holding remarkable promise for personalized medicine and public health.
The concept of intrinsic capacity was pioneered by the World Health Organization (WHO) and officially integrated into the International Classification of Diseases (ICD-11) in 2022, marking a paradigm shift in how aging and its associated declines are clinically recognized. Rather than seeking to return older adults to an unattainable disease-free state, this framework prioritizes the preservation and enhancement of function, a goal that resonates strongly with the lived experiences and priorities of the aging population. In this context, the IC Clock is poised to become an essential tool, offering an objective molecular biomarker that quantitatively reflects the multidimensional aspects of physiological and cognitive function that decline with age.
The development of the IC Clock was spearheaded by experts at the Buck Institute for Research on Aging in the United States, in cooperation with the IHU HealthAge in France, alongside the French National Institute of Health and Medical Research (INSERM) and the University of Montpellier. This transatlantic partnership exemplifies the increasingly global nature of longevity science and highlights the collaborative effort required to tackle the complexity of aging. Central to the model’s development was the rich data set derived from the INSPIRE-T cohort, encompassing 1,000 individuals ranging in age from 20 to 102 years old. This longitudinal study, based in Toulouse, France, offers an unparalleled repository of clinical, functional, lifestyle, and biospecimen data collected annually over several years, including blood, urine, saliva, and dental plaque samples.
At the core of the IC Clock’s methodology lies the utilization of DNA methylation patterns—epigenetic modifications that serve as molecular fingerprints of biological aging processes. These methylation signatures, accessible through non-invasive blood or saliva samples, provide a dynamic readout of an individual’s intrinsic capacity status. By training the IC Clock model on the INSPIRE-T cohort data, researchers achieved a robust and fine-tuned predictor of functional aging. The clock was subsequently validated using the well-established Framingham Heart Study, a longitudinal cohort renowned for its contributions to cardiovascular and aging research, affirming the model’s predictive power across diverse populations.
Remarkably, the IC Clock not only correlates with biological age but also outperforms previous first- and second-generation epigenetic aging clocks when it comes to predicting all-cause mortality. This suggests that the IC Clock captures core biological processes and hallmarks that are tightly intertwined with lifespan and healthspan. Furthermore, higher IC Clock scores have been linked with enhanced immune function, reduced systemic inflammation, and favorable lifestyle factors such as diet and physical activity. These correlations bolster the clock’s utility as a biomarker that integrates functional, immunological, and environmental dimensions of aging, providing a holistic metric that could revolutionize geriatric assessment.
Recognizing the practical challenges of invasive sampling, the research team is advancing a dried blood spot (DBS) assay adaptation for the IC Clock. This innovation significantly minimizes the logistical and financial burdens associated with clinic-based blood draws, enabling broader deployment of the tool in low- and middle-income countries where healthcare access is limited. Such scalability is crucial for global aging research and public health initiatives, as it permits earlier detection of functional decline and facilitates individualized intervention, potentially mitigating disability and improving the quality of life in aging populations worldwide.
Despite the World Health Organization’s endorsement of intrinsic capacity decline as a diagnostic entity, regulatory acceptance—particularly by the United States Food and Drug Administration (FDA)—remains elusive. This gap poses a bottleneck in clinical translation efforts aimed at approving therapies that target biological aging processes. David Furman, PhD, senior author and director of the Buck Bioinformatics and Data Science Core, envisions the IC Clock as a decisive instrument capable of bridging this divide. By providing quantifiable, actionable endpoints tied directly to functional outcomes, the IC Clock could accelerate regulatory pathways and shift the discourse regarding aging—potentially reframing it as a treatable condition rather than an inevitable decline.
Looking forward, the IC Clock is slated for integration into the ambitious XPRIZE Healthspan competition, a seven-year global initiative with $101 million in prize money, dedicated to extending human healthspan. The competition challenges teams to restore key functional domains—muscle, cognition, and immune resilience—by at least a decade, with an aspirational target of 20 years, in individuals aged 50 to 80 years within a single year. The Buck Institute, in partnership with IHU HealthAge, has been named a semifinalist, proposing a hybrid intervention paradigm combining the metabolic regulator ketone esters with ICOPE-INTENSE, a comprehensive regimen involving exercise, cognitive training, and nutritional strategies targeted at enhancing intrinsic capacity.
ICOPE-INTENSE represents the most rigorous non-pharmacological intervention to date focused on functional preservation and enhancement in aging adults. The IC Clock’s role in this trial will be to provide a precise molecular and functional readout of therapeutic efficacy, enabling real-time tracking of intervention impact. Success in this arena could not only validate the clock but also catalyze adoption of precision aging medicine and usher in a new era in longevity research that focuses on extending healthy, functional years rather than mere lifespan.
This transformative research was supported by a robust network of funding, including grants from the European Regional Development Fund, the French National Research Agency as part of the France 2030 initiative, and the National Institutes of Health in the United States. The INSPIRE-T cohort continues to serve as a critical resource underpinning these advances in epigenetic biomarker discovery, underscoring the value of longitudinal, interdisciplinary studies in unraveling the complexities of aging biology.
In summary, the IC Clock stands as a milestone in aging research, offering a biologically grounded, clinically relevant, and scalable tool for assessing intrinsic capacity across diverse populations. By shifting the focus from static chronological age or isolated diseases to a dynamic measure of how well individuals maintain function, it promises to transform diagnostics, intervention strategies, and regulatory frameworks. The implications are profound, heralding a future in which aging is managed proactively, improving quality of life and healthspan on a global scale.
Subject of Research: People
Article Title: A Novel Blood-Based Epigenetic Clock for Intrinsic Capacity Predicts Mortality and is Associated with Clinical, Immunological and Lifestyle Factors
News Publication Date: 4-Jun-2025
Web References: http://dx.doi.org/10.1038/s43587-025-00883-5
References:
Furman, D. et al. A Novel Blood-Based Epigenetic Clock for Intrinsic Capacity Predicts Mortality and is Associated with Clinical, Immunological and Lifestyle Factors. Nature Aging (2025). DOI: 10.1038/s43587-025-00883-5
Keywords: Health and medicine, Bioinformatics, Computational biology, Immune system
