International Journal of Bioscience and Biochemistry · Mar 2026

The role of mitochondrial dysfunction in aging and disease: Biochemical mechanisms

By O'Brien D

One observation that continues to puzzle gerontologists is deceptively simple: why do mitochondria-the organelles our cells depend on for virtually all aerobic energy production-seem to deteriorate in such a predictable, almost programmatic fashion as organism’s age? This research set out to explore the biochemical underpinnings of age-associated mitochondrial decline by measuring key indicators of mitochondrial function across four distinct participant groups representing healthy young adults, healthy middle-aged individuals, healthy elderly persons, and patients diagnosed with age-related degenerative diseases, all recruited at two Irish academic medical centers between February 2020 and October 2021. We enrolled 194 participants and obtained peripheral blood mononuclear cell samples for assessment of mitochondrial membrane potential, reactive oxygen species generation kinetics, mitochondrial DNA copy number, respiratory chain complex activities, and circulating biomarkers of mitochondrial stress including cell-free mitochondrial DNA and growth differentiation factor 15 concentrations. Our exploratory analysis revealed a progressive and statistically significant decline in mitochondrial membrane potential with advancing age among healthy participants (Pearson r=-0.71, p

doi.org/10.33545/26646536.2026.v8.i3a.185Open accessMechanisms