Lifestyle-Associated Biomarkers of Cellular and Whole-Organism Aging: A Practical Roadmap for Human Geroscience Trials
9 affiliations
- 1Department of Science and Engineering, College of Nanotechnology, SUNY Albany, Albany, NY 12222, USA
- 2Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008 Kazan, Russia
- 3Division of Medical and Biological Sciences, Tatarstan Academy of Sciences, 420111 Kazan, Russia
- 4Advanced Biotherapeutics Ltd., 20–22, Wenlock Road, London N1 7GU, UK
- 5Uppsala Inc., 67 Shady Brook Drive, Colora, MD 21917, USA
- 6Preventive Medicine Center (PMC), 1000 Asylum Avenue, #2109, Hartford, CT 06105, USA
- 7Pyunkang Korean Medicine Hospital, 21 Seon-ro 1-gil, Seocho-gu, Seoul 06733, Republic of Korea
- 8Department Pharmacology, Faculty of Pharmacy, University of Debrecen, Nagyerdei krt. 98, 4032 Debrecen, Hungary
- 9HUN-REN-UD Pharmamodul Research Group, Faculty of Pharmacy, University of Debrecen, Nagyerdei krt. 98, 4032 Debrecen, Hungary
Abstract
Aging is a multidimensional biological process that is not adequately captured by chronological age alone. Geroscience—the study of biological mechanisms that drive age-related functional decline and disease susceptibility—therefore requires biomarker frameworks that can identify biological aging trajectories and assess whether lifestyle-associated interventions meaningfully influence aging-related pathways. In this review, we propose a practical, mechanism-based framework for studying lifestyle-associated effects on cellular and whole-organism aging in humans. We examine major biomarker domains, including DNA-methylation-based epigenetic aging clocks, cellular senescence-associated measures, senescence-associated secretory phenotype factors, inflammaging mediators, oxidative stress indicators, mitochondrial function, metabolic and nutrient-sensing pathways, proteomic and metabolomic signatures, microbiome-associated markers, and functional measures of frailty, mobility, cognition, and resilience. We also discuss criteria for biomarker selection in exploratory and multicenter trials, emphasizing biological relevance, analytical validity, responsiveness to intervention, feasibility, reproducibility, and clinical interpretability. Finally, we outline a practical study-design roadmap integrating biospecimen collection, repeated assessments, core and exploratory biomarker panels, and functional endpoints. A biomarker-guided geroscience strategy may provide a practical route for connecting mechanistic aging biology with clinically relevant human studies designed to preserve healthspan and functional independence.
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BibTeX
@article{rose2026lifestyleassociated,
title = {{Lifestyle-Associated Biomarkers of Cellular and Whole-Organism Aging: A Practical Roadmap for Human Geroscience Trials}},
author = {Stephen C. Rose and Albert A. Rizvanov and Donald D. Haines and Fred M. Cowan and Robert H. Silverstein and Fadia F. Mahmoud and Valeriya V. Solovyeva and Kristina V. Kitaeva and Seo Hyo-Seok and Arpad Tosaki},
journal = {Biomolecules},
year = {2026},
month = oct,
doi = {10.3390/biom16101504},
url = {https://www.mdpi.com/2218-273X/16/10/1504},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Lifestyle-Associated Biomarkers of Cellular and Whole-Organism Aging: A Practical Roadmap for Human Geroscience Trials
AU - Stephen C. Rose
AU - Albert A. Rizvanov
AU - Donald D. Haines
AU - Fred M. Cowan
AU - Robert H. Silverstein
AU - Fadia F. Mahmoud
AU - Valeriya V. Solovyeva
AU - Kristina V. Kitaeva
AU - Seo Hyo-Seok
AU - Arpad Tosaki
PY - 2026
DA - 2026/10/01
JO - Biomolecules
DO - 10.3390/biom16101504
UR - https://www.mdpi.com/2218-273X/16/10/1504
AB - Aging is a multidimensional biological process that is not adequately captured by chronological age alone. Geroscience—the study of biological mechanisms that drive age-related functional decline and disease susceptibility—therefore requires biomarker frameworks that can identify biological aging trajectories and assess whether lifestyle-associated interventions meaningfully influence aging-related pathways. In this review, we propose a practical, mechanism-based framework for studying lifestyle-associated effects on cellular and whole-organism aging in humans. We examine major biomarker domains, including DNA-methylation-based epigenetic aging clocks, cellular senescence-associated measures, senescence-associated secretory phenotype factors, inflammaging mediators, oxidative stress indicators, mitochondrial function, metabolic and nutrient-sensing pathways, proteomic and metabolomic signatures, microbiome-associated markers, and functional measures of frailty, mobility, cognition, and resilience. We also discuss criteria for biomarker selection in exploratory and multicenter trials, emphasizing biological relevance, analytical validity, responsiveness to intervention, feasibility, reproducibility, and clinical interpretability. Finally, we outline a practical study-design roadmap integrating biospecimen collection, repeated assessments, core and exploratory biomarker panels, and functional endpoints. A biomarker-guided geroscience strategy may provide a practical route for connecting mechanistic aging biology with clinically relevant human studies designed to preserve healthspan and functional independence.
SN - 2218-273X
ER -