Problems of ageing and longevity
Оцінка маркерів мітохондріальної дисфункції та метаболічних змін у людей старшого віку: зв’язок із біологічним старінням та станом здоров’я
By М. Yena.
Abstract
Aging is a complex multifactorial process characterized by the progressive accumulation of molecular and cellular damage, a decline in the functional reserve of the organism, and an increased risk of age-related diseases. Mitochondrial dysfunction is considered one of the key mechanisms determining the rate of biological aging and is manifested by impaired oxidative phosphorylation, reduced efficiency of adenosine triphosphate (ATP) synthesis, alterations in redox homeostasis, accumulation of mitochondrial DNA (mtDNA) damage, and disturbances in mitochondrial biogenesis, dynamics, and mitophagy.The aim of this review was to systematize current scientific evidence on biomarkers of mitochondrial dysfunction and associated metabolic alterations in older adults and to determine their potential relationships with biological aging, functional status, and the risk of developing age-related diseases. Particular attention was given to mitochondrial DNA copy number, mtDNA mutational burden and heteroplasmy, circulating cell-free mitochondrial DNA (cf-mtDNA), growth differentiation factor 15 (GDF-15), fibroblast growth factor 21 (FGF-21), markers of oxidative stress and antioxidant defense, alterations in lactate–pyruvate and NAD+/NADH homeostasis, as well as molecular regulators of mitochondrial biogenesis, dynamics, and mitophagy.Analysis of current research indicates that age-related alterations in mitochondrial function are closely associated with reduced physical performance, sarcopenia, frailty, insulin resistance, metabolic disturbances, cardiovascular diseases, and neurodegenerative disorders. GDF-15 and FGF-21 appear to be among the most promising circulating biomarkers of mitochondrial stress; however, their diagnostic value is limited by insufficient specificity and their dependence on comorbid conditions. Mitochondrial DNA copy number may also reflect the degree of molecular aging; nevertheless, its levels are influenced by blood cell composition, metabolic status, inflammatory processes, and lifestyle factors.The available evidence demonstrates that no single mitochondrial or metabolic parameter can be regarded as a universal biomarker of biological age. The greatest potential lies in an integrated multimarker approach combining measures of mitochondrial function, metabolic profile, oxidative stress, systemic inflammation, and clinical and functional status. The development and subsequent validation of such integrated biomarker panels may enable a more accurate assessment of the rate of biological aging, facilitate the early identification of individuals at increased risk of frailty and multimorbidity, and contribute to the development of personalized strategies aimed at promoting healthy longevity.




