A team of international researchers has developed a new biological age "clock" that estimates how well someone is aging, not just how "old" they or their various organs might be. The IC Clock, which is described in a study in Nature Aging, measures intrinsic capacity (IC), the sum of six key functions that determine healthy aging: mobility, cognition, mental health, vision, hearing and nutrition/vitality.
"Maintaining function during the aging process is what matters to older adults. Function should inform medical care instead of focusing on getting patients to some disease-free state," said senior author David Furman, PhD , Buck associate professor and director of the Buck Bioinformatics and Data Science Core. The World Health Organization (WHO) developed the concept of intrinsic capacity and recognized its decline with aging as a condition in 2022 in the International Classification of Diseases ICD-11.
The IC Clock was developed by scientists at the Buck, IHU HealthAge (France) in collaboration with the French INSERM and Universite de Montpellier, reflecting a growing alliance between US and European researchers to advance the science of healthy longevity. Collaborators began developing the IC Clock by utilizing data from the INSPIRE-T cohort consisting of 1000 individuals (age 20 to 102) in and around Toulouse, France with follow-up over 4 years out of 10 so far. In addition to data based on physical and cognitive function as well as lifestyle factors, researchers also had access to biospecimens including blood, urine, saliva, and dental plaque that are collected annually.
The IC Clock uses DNA methylation, a molecular signal found in blood or saliva, to assess IC non-invasively. After training the new model on data from the INSPIRE-T cohort, the team validated it using the Framingham Heart Study, a long-term, ongoing cardiovascular cohort study of residents of the city of Framingham, Massachusetts. Furman says the IC Clock, which factors in all of the currently recognized hallmarks of aging, outperformed all first- and second-generation aging clocks in predicting overall mortality. He also noted that the research found links between higher IC Clock scores and better immune system performance, reduced inflammation and healthier lifestyle choices, suggesting that this measure taps into the core biology of aging and could be useful in the assessment of longevity-promoting interventions.
Furman's team is developing a dried-blood spot solution for the IC Clock, which would reduce the need for labor intensive clinic visits, making the IC Clock useful for assessing functional decline in low-and-middle income countries. "If we can offer a scalable, affordable molecular level tool to assess functional decline, the IC Clock could help clinicians, researchers, and policy makers better identify at-risk individuals and tailor interventions that promote a longer healthier life," he said.
While WHO has adopted a decline in IC as a diagnostic for aging, the US FDA has yet to tackle the issue, creating what some see as a bottleneck in efforts to get clinical treatments approved to address biological aging. Furman thinks the IC Clock could provide a way to end the long-standing argument as to whether aging should be classified as a disease. "We hope the IC Clock will ultimately enable the FDA to approve treatments that would improve health and function in older adults."
The IC Clock will be utilized in the XPRIZE Healthspan competition . The Buck and colleagues from Hospital-University Institute HealthAge at the University of Toulouse, have been named semifinalists for the 7-year, $101 million global competition, which is aimed at revolutionizing how we approach human aging. Competing teams are tasked with developing and testing modalities that restore muscle, cognition, and immune function by a minimum of 10 years, with an ambitious goal of 20 years, in persons aged 50-80 years, in one year or less.
The Buck-Toulouse team is proposing a hybrid intervention that combines taking a daily ketone ester with a personalized intervention called ICOPE-INTENSE, which spans exercise, cognitive training, nutrition and more. The IC Clock will be used to track and analyze responses among participants. ICOPE-INTENSE is the most robust non-drug intervention to date designed to improve Intrinsic Capacity.
CITATION: A Novel Blood-Based Epigenetic Clock for Intrinsic Capacity Predicts Mortality and is Associated with Clinical, Immunological and Lifestyle Factors
DOI: 10.1038/s43587-025-00883-5
Coauthors: Buck postdoc Matias Fuentealba is the first author of the paper. Other collaborators include Laure Rouch, Sophie Guyonnet, Philipe de Souto Barreto, Sandrine Andrieu and Bruno Vellas, IHU HealthAge, Toulouse, France; and Jean-Marc Lemaitre, INSERM IRMB UMR1183, Hôpital Saint Eloi, Université de Montpellier, Montpellier, France
Acknowledgments:
The INSPIRE-T study was supported by grants from the Region Occitanie/PyrénéesMéditerranée (Reference number: 1901175), the European Regional Development Fund (ERDF) (Project number: MP0022856), the Inspire Chairs of Excellence funded by: Alzheimer Prevention in Occitania and Catalonia (APOC), EDENIS, KORIAN, Pfizer, Pierre-Fabre, and the IHU HealthAge which received funding from the French National Research Agency (ANR) as part of the France 2030 program (reference number: ANR-23-IAHU-0011). This work was supported by the National Institutes of Health (NIH) through grants U01 AG086214 and R03 OD036497.
About the Buck Institute for Research on Aging
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