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Cited by 51Epigenetics and DNA MethylationGenetics, Aging, and Longevity in Model OrganismsTelomeres, Telomerase, and Senescence

A blood-based epigenetic clock for intrinsic capacity predicts mortality and is associated with clinical, immunological and lifestyle factors

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Fuentealba, Matías, Rouch, Laure, Guyonnet, Sophie, Lemaitre, Jean-Marc, de Souto Barreto, Philipe, Vellas, Bruno, Andrieu, Sandrine, Furman, David·2025·Nature Aging
DOI 10.1038/s43587-025-00883-5PMC PMC12270914

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Abstract

Age-related decline in intrinsic capacity (IC), defined as the sum of an individual’s physical and mental capacities, is a cornerstone for promoting healthy aging by prioritizing maintenance of function over disease treatment. However, assessing IC is resource-intensive, and the molecular and cellular bases of its decline are poorly understood. Here we used the INSPIRE-T cohort (1,014 individuals aged 20–102 years) to construct the IC clock, a DNA methylation-based predictor of IC, trained on the clinical evaluation of cognition, locomotion, psychological well-being, sensory abilities and vitality. In the Framingham Heart Study, DNA methylation IC outperforms first-generation and second-generation epigenetic clocks in predicting all-cause mortality, and it is strongly associated with changes in molecular and cellular immune and inflammatory biomarkers, functional and clinical endpoints, health risk factors and lifestyle choices. These findings establish the IC clock as a validated tool bridging molecular readouts of aging and clinical assessments of IC.

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  • Methylation barcodes and epigenetic clocks represent the latest advancements in the field.

    “Methylation barcodes and epigenetic clocks represent the latest advancements in the field [58,59,60].”

    From Genetic Insights into the Economic Toll of Cell Line Misidentification: A Comprehensive Review (2026) · cites this paper as [60]

    The Main section describes the development of a DNA methylation-based epigenetic clock, and Results > DNAm-based predictor of IC compares it with established clocks (page numbers not supplied). This supports the epigenetic-clock part of the sentence, but the paper does not discuss methylation barcodes or establish that both are the latest advancements in the field. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

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Authors
Fuentealba, M., Rouch, L., Guyonnet, S., Lemaitre, J.-M., de Souto Barreto, P., Vellas, B., Andrieu, S., & Furman, D.
Affiliations
  • Buck Institute for Research on Aging (US)
  • Université Toulouse III - Paul Sabatier (FR)
Corresponding author
Furman, David
ORCID
Venue
Nature Aging
Publisher
Springer Science and Business Media LLC
Published
2025-06-04
Volume
5
Issue
7
Pages
1207-1216
ISSN
2662-8465 (ISSN-L)
DOI
10.1038/s43587-025-00883-5
PMC
PMC12270914
OpenAlex
W4411036731
Cited by
51
References
7
Citations by year
2026: 37 · 2025: 14
FWCI
15.33
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Aging (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • HAL (submittedVersion, cc-by)
Funders
  • European Commission (MP0022856)
  • Agence Nationale de la Recherche (ANR-23-IAHU-0011)
  • National Institutes of Health (1u01ag086214-01, 1r03od036497-01)
  • Centers for Disease Control and Prevention (R03 OD036497)
  • National Institute on Aging (U01 AG086214)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
Keywords
intrinsic capacity, epigenetic clocks, DNA methylation, all-cause mortality, healthy aging, functional capacity, immunological markers, inflammatory markers, lifestyle factors, Framingham Heart Study, cognitive function, locomotion, vitality
MeSH terms
Adult, Aged, Aged, 80 and over, Aging, Female, Humans, Life Style, Male, Middle Aged, Mortality, Risk Factors, Cohort Studies, Biomarkers, DNA Methylation, Epigenesis, Genetic, Young Adult

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