Adv Gerontol. 2026;39(3):472-482. doi: 10.34922/AE.2026.39.3.020.
ABSTRACT
The purpose of this review is to summarize and critically analyze data on markers of metabolic and mitochondrial stress in atherosclerosis in older and oldest-old patients, highlighting differences between circulating clinical biomarkers, metabolic-epigenetic indicators, and intracellular regulators of mitochondrial quality control, as well as the limitations of age-specific interpretation. An analytical narrative review of the literature was performed using PubMed, Scopus, and Web of Science for 2010-2025; the last control search was conducted on April 27, 2026. The keywords used were signaling molecules, FGF21, GDF15, endothelial dysfunction, mitochondrial dysfunction, lactate, endothelial aging, and cellular senescence. The analysis included 38 sources with a focus on clinical cohorts, age-stratified data, experimental studies on vascular aging, and publications with translational potential. The selection of markers was based on their representation of different levels of the pathological process: systemic stress response, metabolic-epigenetic remodeling, and intracellular mitochondrial quality control. The most clinically relevant circulating candidates are FGF21 (fibroblast growth factor 21) and GDF15 (growth differentiation factor 15). FGF21 is associated with atherosclerotic lesions and cardiovascular risk, but its increase should be interpreted as a reflection of an activated stress response rather than as an independent diagnostic criterion. GDF15 is associated with age, functional decline, comorbidity, and poor prognosis, but it is not a specific marker of atherosclerosis. Lactate and lactylation represent a promising metabolic-epigenetic mechanism linking glycolytic shift, cellular senescence, and vascular inflammation, but evidence of correspondence between circulating and tissue levels is still required. AMPK, PGC-1α, and PINK1/Parkin have predominantly mechanistic significance and should currently be considered intracellular regulators and therapeutic targets rather than clinically validated biomarkers. In atherosclerosis in older and oldest-old patients, markers of metabolic and mitochondrial stress should be assessed within a hierarchical evidence model and with mandatory consideration of age, comorbidity, and treatment-related confounders. FGF21 and GDF15 are the closest to clinical validation; lactate and lactylation represent a promising direction for translational research; AMPK, PGC-1α, and PINK1/Parkin form the pathogenic basis of mitochondrial quality control but require clinically reproducible assessment methods.
PMID:42502945 | DOI:10.34922/AE.2026.39.3.020