Methods for assessing biological age: relevance, clock types, and clinical significance

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

Over the past century, humanity has witnessed an unprecedented increase in life expectancy, which has naturally led to global population aging. Paradoxically, despite the impressive achievements of modern medicine, the prevalence of age-related noncommunicable diseases continues to steadily increase. The fundamental goal of longevity medicine interventions is not simply to increase the number of years lived, but to significantly extend the healthy lifespan (Healthspan), slow the rate of biological aging, and improve quality of life, regardless of an individual’s chronological age. In this context, aging biomarkers represent critical tools for achieving these goals. Biological age is considered by the modern scientific community as the most promising integrated indicator combining biomarker signatures and possessing clinical and prognostic significance in longevity medicine. Epigenetic clocks, based on a thorough analysis of DNA methylation patterns, are currently recognized as the gold standard for quantitative assessment of biological age. Among the most thoroughly studied and validated models are the Horvath clock, the Hannum clock, the PhenoAge formula, the GrimAge formula, and the DunedinPACE formula, each with specific advantages in different clinical contexts. At the same time, the dynamics of many biomarkers throughout the life cycle are distinctly nonlinear and exhibit complex patterns of interaction with a nonlinear increase in mortality and the risk of developing age-associated pathologies. Therefore, the implementation of artificial intelligence technologies for multimodal data analysis opens up fundamentally new prospects for the creation of highly accurate and personalized models for assessing biological age.

About the authors

K. S. Belan

Atlas Medical Center

Author for correspondence.
Email: kirbelan@gmail.com
ORCID iD: 0009-0001-7183-8965

Head of Direction of Preventive Medicine

Russian Federation, Moscow

K. A. Lemberg

Atlas Medical Center

Email: lemberg.ka@atlasclinic.ru
ORCID iD: 0009-0000-9887-8759

General Director

Russian Federation, Moscow

I. R. Fatkhutdinov

Atlas Medical Center

Email: IR_FATHUTDINOV@protek.ru
ORCID iD: 0000-0002-8485-8543

Chief Physician

Russian Federation, Moscow

K. K. Antonov

Atlas Medical Center

Email: antonov.kk@atlasclinic.ru
ORCID iD: 0009-0001-0185-0045

Dr. Sci. (Med.), Head of the Atlas Clinics

Russian Federation, Moscow

N. V. Gryazeva

Central State Medical Academy of the Administrative Directorate of the President of the Russian Federation

Email: tynrik@yandex.ru
ORCID iD: 0000-0003-3437-5233

Dr. Sci. (Med.), Professor, Department of Dermatovenereology and Cosmetology

Russian Federation, Moscow

References

  1. Martinez R., Morsch P., Soliz P., et al. Life expectancy, healthy life expectancy, and burden of disease in older people in the Americas, 1990-2019: a population-based study. Rev Panam Salud Publica. 2021;45:e114. https://doi.org/10.26633/RPSP.2021.114
  2. Ansah J.P., Chiu C.T. Projecting the chronic disease burden among the adult population in the United States using a multi-state population model. Front Public Health. 2023;10:1082183.
  3. Crimmins E.M. Lifespan and Healthspan: Past, Present, and Promise. Gerontologist. 2015;55(6):901–11. https://doi.org/10.1093/geront/gnv130
  4. Bischof E., Scheibye-Knudsen M., Siow R.C., et al. Longevity medicine: upskilling the physicians of tomorrow. The Lancet Healthy Longevity. 2021;2(4):e187–8.
  5. Pokushalov E., Ponomarenko A., Shrainer, E., et al. Biomarker-Guided Dietary Supplementation: A Narrative Review of Precision in Personalized Nutrition. Nutrients. 2024;16:4033. https://doi.org/10.3390/nu16234033
  6. López-Otín C., Blasco M.A., Partridge L., et al. Hallmarks of aging: An expanding universe. Cell. 2023;186(2):243–78. https://doi.org/10.1016/j.cell.2022.11.001
  7. Gladyshev V.N., Kritchevsky S.B., Clarke S.G., et al. Molecular damage in aging. Nat. Aging 2021;1:1096–106. 10.1038/s43587-021-00150-3
  8. Moqri M., Herzog C., Poganik J.R.; Biomarkers of Aging Consortium; Biomarkers of aging for the identification and evaluation of longevity interventions. Cell. 2023;186(18):3758–75. https://doi.org/10.1016/j.cell.2023.08.003
  9. Hartmann A., Hartmann C., Secci R., et al. Ranking Biomarkers of Aging by Citation Profiling and Effort Scoring. Front Genet. 2021;12:686320. https://doi.org/10.3389/fgene.2021.686320
  10. Lyu Y.X., Fu Q., Wilczok D., et al. Longevity biotechnology: bridging AI, biomarkers, geroscience and clinical applications for healthy longevity. Aging (Albany NY). 2024;16(20):12955–76. doi: 10.18632/aging.206135
  11. Levine M.E., et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY). 2018;10(4):573–91.
  12. Zheng Z., Li J., Liu T., et al. DNA methylation clocks for estimating biological age in Chinese cohorts. Protein Cell. 2024;15(8):575–93. https://doi.org/10.1093/procel/pwae011
  13. Yusri K., Kumar S., Fong S., et al. Towards Healthy Longevity: Comprehensive Insights from Molecular Targets and Biomarkers to Biological Clocks. Int J Mol Sci. 2024;25(12):6793. https://doi.org/10.3390/ijms25126793
  14. Sabbatinelli J., Giuliani A., Kwiatkowska K.M., et al. DNA Methylation-derived biological age and long-term mortality risk in subjects with type 2 diabetes. Cardiovasc Diab. 2024;23:250. https://doi.org/10.1186/s12933-024-02351-7
  15. Kurbanov D.B., Ahangari F., Adams T., et al. Epigenetic age acceleration in idiopathic pulmonary fibrosis revealed by DNA methylation clocks. Am J Physiol Lung Cell Mol Physiol. 2025;328(3):L456–62. https://doi.org/10.1152/ajplung.00171.2024
  16. Yaskolka Meir A., Keller M., Hoffmann A. et al. The effect of polyphenols on DNA methylation-assessed biological age attenuation: the DIRECT PLUS randomized controlled trial. BMC Med 2023;21:364. https://doi.org/10.1186/s12916-023-03067-3
  17. Bell C.G., Lowe R., Adams P.D., et al. DNA methylation aging clocks: challenges and recommendations. Genome Biol. 2019;20:249. https://doi.org/10.1186/s13059-019-1824-y

Supplementary files

Supplementary Files
Action
1. JATS XML

Согласие на обработку персональных данных

 

Используя сайт https://journals.rcsi.science, я (далее – «Пользователь» или «Субъект персональных данных») даю согласие на обработку персональных данных на этом сайте (текст Согласия) и на обработку персональных данных с помощью сервиса «Яндекс.Метрика» (текст Согласия).