RESTING HEART RATE AS A BIOMARKER OF BIOLOGICAL AGING: A REVIEW AND SYNTHESIS
Abstract
Research objectives: The objective of this study was to synthesise evidence on resting heart rate (RHR) and heart rate variability (HRV) as biomarkers of biological aging, with a focus on their relationships to multisystem physiological decline across cardiovascular, metabolic, autonomic, and inflammatory domains.
Methods: A structured literature search was conducted. Included publications comprised population-based cohorts, mechanistic studies, biomarker analyses, and autonomic assessments evaluating associations between RHR, HRV, biological aging markers, morbidity, and mortality.
Key findings: Elevated RHR consistently aligned with signatures of accelerated aging, including adverse cardiometabolic profiles, reduced autonomic flexibility, and increased inflammatory activation. Higher RHR was associated with older brain age, diminished functional resilience, and biomarker patterns characteristic of inflammaging, such as heightened interleukin-6 and tumour necrosis factor-α. Lower RHR corresponded to slower biological aging trajectories. HRV analyses complemented these findings, linking reduced parasympathetic activity and lower variability with diminished physiological adaptability and greater aging burden.
Conclusions: RHR emerges as a robust, multidimensional biomarker that integrates signals of cumulative physiological decline and reliably identifies individuals exhibiting accelerated biological aging. Its consistent associations with molecular, functional, and clinical indicators of aging highlight its value as a practical, noninvasive tool for assessing multisystem health status.
References
Altini, M., & Plews, D. (2021). What Is behind Changes in Resting Heart Rate and Heart Rate Variability? A Large-Scale Analysis of Longitudinal Measurements Acquired in Free-Living. Sensors, 21(23), 7932. https://doi.org/10.3390/s21237932
Anselmino, M., Ohrvik, J., Rydén, L., & Euro Heart Survey Investigators. (2010). Resting heart rate in patients with stable coronary artery disease and diabetes: A report from the euro heart survey on diabetes and the heart. European Heart Journal, 31(24), 3040–3045. https://doi.org/10.1093/eurheartj/ehq368
Cao, Y., Li, S., Zha, Y., Yan, X., Jia, J., Luo, Y., & Chi, A. (2025). Effects of different incremental treadmill exercise protocols on the autonomic nervous system in healthy college students: A comparative study based on heart rate variability analysis. Frontiers in Physiology, 16, 1579929. https://doi.org/10.3389/fphys.2025.1579929
Chen, X., Barywani, S. B., Hansson, P.-O., Östgärd Thunström, E., Rosengren, A., Ergatoudes, C., Mandalenakis, Z., Caidahl, K., & Fu, M. L. (2019). Impact of changes in heart rate with age on all-cause death and cardiovascular events in 50-year-old men from the general population. Open Heart, 6(1), e000856. https://doi.org/10.1136/openhrt-2018-000856
Cui, X., Mandalenakis, Z., Thunström, E., Fu, M., Svärdsudd, K., & Hansson, P.-O. (2021). The impact of time-updated resting heart rate on cause-specific mortality in a random middle-aged male population: A lifetime follow-up. Clinical Research in Cardiology, 110(6), 822–830. https://doi.org/10.1007/s00392-020-01714-w
Demir, V., Yılmaz, S., Ede, H., & Turan, Y. (2019). Correlation of Resting Heart Rate with the Severity and Complexity of Coronary Artery Disease: A Single-Center Retrospective Study. International Journal of Preventive Medicine, 10(1). https://doi.org/10.4103/ijpvm.IJPVM_347_18
Department of Research and Innovation, Edem Medical Center, Strilky, Ukraine, Bashkirtsev, O., Sagan, V., National Technical University of Ukraine «Igor Sikorsky Kyiv Polytechnic Institute, Kyiv, Ukraine, Mawi International, Clearwater, Florida, USA, Gaevska, V., Department of Research and Innovation, Edem Medical Center, Strilky, Ukraine, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine, Zimba, O., Danylo Halytsky Lviv National Medical University, Lviv, Ukraine, & Department of Research and Innovation, Edem Medical Center, Strilky, Ukraine. (2021). BIOLOGICAL AGE ESTIMATION BASED ON HEART RATE VARIABILITY: A PILOT STUDY. Proceedings of the Shevchenko Scientific Society. Medical Sciences, 65(2). https://doi.org/10.25040/ntsh2021.02.21
Eggenberger, P., Annaheim, S., Kündig, K. A., Rossi, R. M., Münzer, T., & De Bruin, E. D. (2020). Heart Rate Variability Mainly Relates to Cognitive Executive Functions and Improves Through Exergame Training in Older Adults: A Secondary Analysis of a 6-Month Randomized Controlled Trial. Frontiers in Aging Neuroscience, 12, 197. https://doi.org/10.3389/fnagi.2020.00197
Elliott, M. L., Caspi, A., Houts, R. M., Ambler, A., Broadbent, J. M., Hancox, R. J., Harrington, H., Hogan, S., Keenan, R., Knodt, A., Leung, J. H., Melzer, T. R., Purdy, S. C., Ramrakha, S., Richmond-Rakerd, L. S., Righarts, A., Sugden, K., Thomson, W. M., Thorne, P. R., … Moffitt, T. E. (2021). Disparities in the pace of biological aging among midlife adults of the same chronological age have implications for future frailty risk and policy. Nature Aging, 1(3), 295–308. https://doi.org/10.1038/s43587-021-00044-4
Forte, G., Favieri, F., & Casagrande, M. (2019). Heart Rate Variability and Cognitive Function: A Systematic Review. Frontiers in Neuroscience, 13, 710. https://doi.org/10.3389/fnins.2019.00710
Garger, D., Meinel, M., Dietl, T., Hillig, C., Garzorz‐Stark, N., Eyerich, K., De Angelis, M. H., Eyerich, S., & Menden, M. P. (2023). The impact of the cardiovascular component and somatic mutations on ageing. Aging Cell, 22(10), e13957. https://doi.org/10.1111/acel.13957
Gaye, B., Valentin, E., Xanthakis, V., Perier, M.-C., Celermajer, D. S., Shipley, M., Marijon, E., Song, R. J., Empana, J.-P., Ramachandran, V. S., & Jouven, X. (2024). Association between change in heart rate over years and life span in the Paris Prospective 1, the Whitehall 1, and Framingham studies. Scientific Reports, 14(1), 20052. https://doi.org/10.1038/s41598-024-70806-8
Gonzales, T. I., Jeon, J. Y., Lindsay, T., Westgate, K., Perez-Pozuelo, I., Hollidge, S., Wijndaele, K., Rennie, K., Forouhi, N., Griffin, S., Wareham, N., & Brage, S. (2023). Resting heart rate is a population-level biomarker of cardiorespiratory fitness: The Fenland Study. PLOS ONE, 18(5), e0285272. https://doi.org/10.1371/journal.pone.0285272
Goorakani, Y., Sedigh Rahimabadi, M., Dehghan, A., Kazemi, M., Chijan, M. R., Bijani, M., Shahraki, H. R., Davoodi, A., Farjam, M., & Homayounfar, R. (2020a). Correlation of resting heart rate with anthropometric factors and serum biomarkers in a population-based study: Fasa PERSIAN cohort study. BMC Cardiovascular Disorders, 20(1), 319. https://doi.org/10.1186/s12872-020-01594-y
Goorakani, Y., Sedigh Rahimabadi, M., Dehghan, A., Kazemi, M., Chijan, M. R., Bijani, M., Shahraki, H. R., Davoodi, A., Farjam, M., & Homayounfar, R. (2020b). Correlation of resting heart rate with anthropometric factors and serum biomarkers in a population-based study: Fasa PERSIAN cohort study. BMC Cardiovascular Disorders, 20(1), 319. https://doi.org/10.1186/s12872-020-01594-y
Grassi, G., Arenare, F., Quarti-Trevano, F., Seravalle, G., & Mancia, G. (2009). Heart rate, sympathetic cardiovascular influences, and the metabolic syndrome. Progress in Cardiovascular Diseases, 52(1), 31–37. https://doi.org/10.1016/j.pcad.2009.05.007
Hernández-Vicente, A., Hernando, D., Santos-Lozano, A., Rodríguez-Romo, G., Vicente-Rodríguez, G., Pueyo, E., Bailón, R., & Garatachea, N. (2020). Heart Rate Variability and Exceptional Longevity. Frontiers in Physiology, 11, 566399. https://doi.org/10.3389/fphys.2020.566399
Imahori, Y., Vetrano, D. L., Xia, X., Grande, G., Ljungman, P., Fratiglioni, L., & Qiu, C. (2022). Association of resting heart rate with cognitive decline and dementia in older adults: A population-based cohort study. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, 18(10), 1779–1787. https://doi.org/10.1002/alz.12495
Jensen, M. T. (2019). Resting heart rate and relation to disease and longevity: Past, present and future. Scandinavian Journal of Clinical and Laboratory Investigation, 79(1–2), 108–116. https://doi.org/10.1080/00365513.2019.1566567
Jensen, M. T., Suadicani, P., Hein, H. O., & Gyntelberg, F. (2013). Elevated resting heart rate, physical fitness and all-cause mortality: A 16-year follow-up in the Copenhagen Male Study. Heart, 99(12), 882–887. https://doi.org/10.1136/heartjnl-2012-303375
Kim, J. (2018). ASSOCIATION BETWEEN TINNITUS AND MENTAL HEALTH AMONG KOREAN ADOLESCENTS: THE KOREA NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY. CENTRAL EUROPEAN JOURNAL OF PUBLIC HEALTH, 26(1), 65–70. https://doi.org/10.21101/cejph.a4514
Lohman, T., Bains, G., Berk, L., & Lohman, E. (2021). Predictors of Biological Age: The Implications for Wellness and Aging Research. Gerontology and Geriatric Medicine, 7, 23337214211046419. https://doi.org/10.1177/23337214211046419
MacDonald, E. A., Rose, R. A., & Quinn, T. A. (2020). Neurohumoral Control of Sinoatrial Node Activity and Heart Rate: Insight From Experimental Models and Findings From Humans. Frontiers in Physiology, 11, 170. https://doi.org/10.3389/fphys.2020.00170
Maduro, P. A., Maduro, L. A. R., Lima, P. E., Silva, A. C. C., Silva, R. D. C. M. D., Rocha, A. S. L., Ribeiro, M. J. S., Matoso, J. M. D., Bavaresco Gambassi, B., & Schwingel, P. A. (2025). Cardiac Autonomic Modulation and Cognitive Performance in Community-Dwelling Older Adults: A Preliminary Study. Neurology International, 17(5), 74. https://doi.org/10.3390/neurolint17050074
Manimaran, G., Puthusserypady, S., Dominguez, H., & Bardram, J. E. (2025). Cardiovascular Risk Assessment via Sleep Patterns and ECG-Based Biological Age Estimation. Journal of Clinical Medicine, 14(10), 3339. https://doi.org/10.3390/jcm14103339
Mao, M., Liu, R., Dong, Y., Wang, C., Ren, Y., Tian, N., Tang, S., Hou, T., Cong, L., Wang, Y., Du, Y., & Qiu, C. (2023). Resting heart rate, cognitive function, and inflammation in older adults: A population-based study. Aging Clinical and Experimental Research, 35(11), 2821–2829. https://doi.org/10.1007/s40520-023-02576-8
Nanchen, D., Stott, D. J., Gussekloo, J., Mooijaart, S. P., Westendorp, R. G. J., Jukema, J. W., Macfarlane, P. W., Cornuz, J., Rodondi, N., Buckley, B. M., Ford, I., Sattar, N., de Craen, A. J. M., & Group, on behalf of the P. (2013a). Resting heart rate and incident heart failure and cardiovascular mortality in older adults: Role of inflammation and endothelial dysfunction: the PROSPER study. European Journal of Heart Failure, 15(5), 581–588. https://doi.org/10.1093/eurjhf/hfs195
Nanchen, D., Stott, D. J., Gussekloo, J., Mooijaart, S. P., Westendorp, R. G. J., Jukema, J. W., Macfarlane, P. W., Cornuz, J., Rodondi, N., Buckley, B. M., Ford, I., Sattar, N., de Craen, A. J. M., & Group, on behalf of the P. (2013b). Resting heart rate and incident heart failure and cardiovascular mortality in older adults: Role of inflammation and endothelial dysfunction: the PROSPER study. European Journal of Heart Failure, 15(5), 581–588. https://doi.org/10.1093/eurjhf/hfs195
Ogliari, G., Mahinrad, S., Stott, D. J., Jukema, J. W., Mooijaart, S. P., Macfarlane, P. W., Clark, E. N., Kearney, P. M., Westendorp, R. G. J., De Craen, A. J. M., & Sabayan, B. (2015). Resting heart rate, heart rate variability and functional decline in old age. Canadian Medical Association Journal, 187(15), E442–E449. https://doi.org/10.1503/cmaj.150462
Ogliari, G., Mahinrad, S., Stott, D. J., Jukema, J. W., Mooijaart, S. P., Macfarlane, P. W., Clark, E. N., Kearney, P. M., Westendorp, R. G. J., de Craen, A. J. M., & Sabayan, B. (2015). Resting heart rate, heart rate variability and functional decline in old age. CMAJ: Canadian Medical Association Journal = Journal de l’Association Medicale Canadienne, 187(15), E442–E449. https://doi.org/10.1503/cmaj.150462
O’Hare, C., Kuh, D., & Hardy, R. (2018). Association of Early-Life Factors With Life-Course Trajectories of Resting Heart Rate: More Than 6 Decades of Follow-up. JAMA Pediatrics, 172(4), e175525. https://doi.org/10.1001/jamapediatrics.2017.5525
Olivieri, F., Biscetti, L., Pimpini, L., Pelliccioni, G., Sabbatinelli, J., & Giunta, S. (2024). Heart rate variability and autonomic nervous system imbalance: Potential biomarkers and detectable hallmarks of aging and inflammaging. Ageing Research Reviews, 101, 102521. https://doi.org/10.1016/j.arr.2024.102521
Park, E., Kim, H., Choi, I., Han, H., Han, K., Jung, H., & Im, G. (2020). Psychiatric Distress as a Common Risk Factor for Tinnitus and Joint Pain: A National Population-Based Survey. CLINICAL AND EXPERIMENTAL OTORHINOLARYNGOLOGY, 13(3), 234–240. https://doi.org/10.21053/ceo.2019.00563
Raisi-Estabragh, Z., Cooper, J., Judge, R., Khanji, M. Y., Munroe, P. B., Cooper, C., Harvey, N. C., & Petersen, S. E. (2020). Age, sex and disease-specific associations between resting heart rate and cardiovascular mortality in the UK BIOBANK. PLOS ONE, 15(5), e0233898. https://doi.org/10.1371/journal.pone.0233898
Raisi-Estabragh, Z., Salih, A., Gkontra, P., Atehortúa, A., Radeva, P., Boscolo Galazzo, I., Menegaz, G., Harvey, N. C., Lekadir, K., & Petersen, S. E. (2022). Estimation of biological heart age using cardiovascular magnetic resonance radiomics. Scientific Reports, 12(1), 12805. https://doi.org/10.1038/s41598-022-16639-9
Rodrigues, E., Lima, D., Barbosa, P., Gonzaga, K., Guerra, R. O., Pimentel, M., Barbosa, H., & Maciel, Á. (2022). HRV Monitoring Using Commercial Wearable Devices as a Health Indicator for Older Persons during the Pandemic. Sensors, 22(5), 2001. https://doi.org/10.3390/s22052001
Schumann, A., & Bär, K.-J. (2022). Autonomic aging – A dataset to quantify changes of cardiovascular autonomic function during healthy aging. Scientific Data, 9(1), 95. https://doi.org/10.1038/s41597-022-01202-y
Schumann, A., Gupta, Y., Gerstorf, D., Demuth, I., Olecka, M., Gaser, C., & Bär, K.-J. (2025, April 17). The autonomic age gap: A machine learning approach to assess biological-calendar age deviations. https://doi.org/10.1101/2025.04.16.25325919
Sebastiani, P., Thyagarajan, B., Sun, F., Schupf, N., Newman, A. B., Montano, M., & Perls, T. T. (2017). Biomarker signatures of aging. Aging Cell, 16(2), 329–338. https://doi.org/10.1111/acel.12557
Speed, C., Arneil, T., Harle, R., Wilson, A., Karthikesalingam, A., McConnell, M., & Phillips, J. (2023). Measure by measure: Resting heart rate across the 24-hour cycle. PLOS Digital Health, 2(4), e0000236. https://doi.org/10.1371/journal.pdig.0000236
Sugden, C., Du Preez, F. B., Olivier, L. R., & Deffur, A. (2023). Wearable-ome meets epigenome: A novel approach to measuring biological age with wearable devices. https://doi.org/10.1101/2023.04.11.536462
Thayer, J. F., Yamamoto, S. S., & Brosschot, J. F. (2010). The relationship of autonomic imbalance, heart rate variability and cardiovascular disease risk factors. International Journal of Cardiology, 141(2), 122–131. https://doi.org/10.1016/j.ijcard.2009.09.543
Vanderlei, L. C. M., Pastre, C. M., Hoshi, R. A., Carvalho, T. D. D., & Godoy, M. F. D. (2009). Noções básicas de variabilidade da frequência cardíaca e sua aplicabilidade clínica. Revista Brasileira de Cirurgia Cardiovascular, 24(2), 205–217. https://doi.org/10.1590/S0102-76382009000200018
Vazir, A., Claggett, B., Cheng, S., Skali, H., Shah, A., Agulair, D., Ballantyne, C. M., Vardeny, O., & Solomon, S. D. (2018). Association of Resting Heart Rate and Temporal Changes in Heart Rate With Outcomes in Participants of the Atherosclerosis Risk in Communities Study. JAMA Cardiology, 3(3), 200–206. https://doi.org/10.1001/jamacardio.2017.4974
Wang, Z., Chen, N., Cao, S., Gao, L., Geok, S. K., & Liu, J. (2025). The effects of balance training on physical fitness and skill-related performance in basketball players: A systematic review. BMC Sports Science, Medicine and Rehabilitation, 17(1), 108. https://doi.org/10.1186/s13102-025-01164-9
Yashin, A. I., Arbeev, K. G., Wu, D., Arbeeva, L. S., Kulminski, A., Akushevich, I., Culminskaya, I., Stallard, E., & Ukraintseva, S. V. (2013). How lifespan associated genes modulate aging changes: Lessons from analysis of longitudinal data. Frontiers in Genetics, 4. https://doi.org/10.3389/fgene.2013.00003
Zhang, Y., Xie, H., He, Z., Zhang, F., Li, L., Wang, N., & Mao, D. (2023). Medical Therapy of Hearing Impairment and Tinnitus with Chinese Medicine: An Overview. CHINESE JOURNAL OF INTEGRATIVE MEDICINE, 29(8), 761–768. https://doi.org/10.1007/s11655-022-3678-5
Views:
0
Downloads:
0
Copyright (c) 2025 Szymon Chmiela, Gabriela Kamińska, Natalia Bołtralik, Julia Dzięcioł, Zuzanna Banaś, Kinga Dzioba, Paulina Kisielewska, Weronika Dmoch, Julia Sawicka, Arkadiusz Moskwa

This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.

