Genetic Aging: Mechanisms, Determinants and Their Role in Human Disease

Abstract

Aging is a universal biological phenomenon characterize by a time-dependent, decline in organismal function, manifested by a gradual increase in risk of disease and death (leading to increased vulnerability to disease and mortality). Age-related genetic and epigenetic changes… are critically implicated in major chronic and degenerative diseases, including cancer, cardiovascular diseases, neurodegenerative conditions, and metabolic syndromes. In this narrative review, we discuss key findings related to molecular mechanisms of aging and maturation processes influenced by intrinsic and extrinsic factors, and we highlight how these interconnected pathways contribute to human disease. An extensive electronic literature search was performed (Google Scholar databases) to include English language articles from 2015 to 2025. Studies have been chosen according to their relevance, scientific value and contribution to explaining genetic mechanisms of aging. The available evidence from the studies reviewed suggests that genetic aging is caused by a still-interacting series of processes, among which are genomic instability, telomere shortening, DNA damage accumulation, epigenomic dysregulation, mitochondrial dysfunction and changes in nutrient-sensing pathways. These phenomena are highly influenced by environmental, lifestyle and social modifications which lead to cellular senescence, tissue degeneration and increased susceptibility to diseases. Furthermore, knowledge from model organisms especially the nematode Caenorhabditis elegans has provided evidence for conserved function of insulin/insulin-like growth factor-1 signaling in life and health span regulation. In Overview, genetic aging may be interpreted as a multicomponent and dynamic process combining the individual genotype with epigenetic or environmental factors. A deeper understanding of these mechanisms is essential for identifying biomarkers of biological aging and developing interventions that enhance healthy aging and reduce age associated disease burden.