Towards Healthy Longevity: Comprehensive Insights from Molecular Targets and Biomarkers to Biological Clocks

Author:

Yusri Khalishah12ORCID,Kumar Sanjay12,Fong Sheng34ORCID,Gruber Jan125,Sorrentino Vincenzo126ORCID

Affiliation:

1. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore

2. Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore

3. Department of Geriatric Medicine, Singapore General Hospital, Singapore 169608, Singapore

4. Clinical and Translational Sciences PhD Program, Duke-NUS Medical School, Singapore 169857, Singapore

5. Science Division, Yale-NUS College, Singapore 138527, Singapore

6. Department of Medical Biochemistry, Amsterdam UMC, Amsterdam Gastroenterology Endocrinology Metabolism and Amsterdam Neuroscience Cellular & Molecular Mechanisms, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands

Abstract

Aging is a complex and time-dependent decline in physiological function that affects most organisms, leading to increased risk of age-related diseases. Investigating the molecular underpinnings of aging is crucial to identify geroprotectors, precisely quantify biological age, and propose healthy longevity approaches. This review explores pathways that are currently being investigated as intervention targets and aging biomarkers spanning molecular, cellular, and systemic dimensions. Interventions that target these hallmarks may ameliorate the aging process, with some progressing to clinical trials. Biomarkers of these hallmarks are used to estimate biological aging and risk of aging-associated disease. Utilizing aging biomarkers, biological aging clocks can be constructed that predict a state of abnormal aging, age-related diseases, and increased mortality. Biological age estimation can therefore provide the basis for a fine-grained risk stratification by predicting all-cause mortality well ahead of the onset of specific diseases, thus offering a window for intervention. Yet, despite technological advancements, challenges persist due to individual variability and the dynamic nature of these biomarkers. Addressing this requires longitudinal studies for robust biomarker identification. Overall, utilizing the hallmarks of aging to discover new drug targets and develop new biomarkers opens new frontiers in medicine. Prospects involve multi-omics integration, machine learning, and personalized approaches for targeted interventions, promising a healthier aging population.

Funder

National University of Singapore

Amsterdam UMC/University of Amsterdam

Publisher

MDPI AG

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