Adv Gerontol. 2026;39(4):579-586. doi: 10.34922/AE.2026.39.4.012.
ABSTRACT
The aim of the study was to evaluate the association between markers of metabolic stress (FGF21, GDF15, and lactate) and mitochondrial stress (p-AMPK, PGC-1α, and PINK1) and clinically significant atherosclerosis in elderly and senile individuals. This pilot comparative cross-sectional study included 310 patients aged 60-89 years. There were 162 patients with clinically verified atherosclerosis and 148 controls without clinically manifested or hemodynamically significant atherosclerotic lesions according to the available clinical and instrumental assessment. Serum levels of FGF21, GDF15, and lactate were measured using enzyme immunoassay and biochemical methods. The expression of p-AMPK, PGC-1α, and PINK1 was assessed by immunocytochemistry of buccal epithelial cells as a non-invasive model of the systemic cellular stress response. In patients with atherosclerosis, there were higher serum levels of FGF21, GDF15, and lactate, lower expression of p-AMPK and PGC-1α, and higher expression of PINK1 compared with age-matched control subgroups (p<0,001). There were the most pronounced changes in patients aged 75-89 years with atherosclerosis. In this subgroup, there were the strongest correlations between FGF21 and PINK1 (r=0,67), GDF15 and p-AMPK (r=-0,61), and FGF21 and PGC-1α (r=-0.63; p<0,001). In multivariable models, there was an independent association between reduced PGC-1α expression and increased FGF21 and GDF15 levels, older age, lower eGFR, type 2 diabetes, and higher BMI. There was also an independent association between increased PINK1 expression and GDF15, lactate, older age, lower eGFR, type 2 diabetes, and higher BMI. In elderly and senile individuals, clinically significant atherosclerosis is associated with a more pronounced profile of metabolic and mitochondrial stress. There are potential research indicators of vascular-metabolic aging among the studied markers; however, their clinical application requires further validation in prospective studies accounting for comorbidity, kidney function, inflammation, and pharmacotherapy.
PMID:42935338 | DOI:10.34922/AE.2026.39.4.012