AUTHOR=Cimmino Fabiano , Petrella Lidia , Cavaliere Gina , Negri Mariarosaria , Pivonello Claudia , Napolitano Giuliana , Crispino Marianna , Trinchese Giovanna , Colao Annamaria , Mollica Maria Pina TITLE=High-Fat Diet Anticipates Age-Related Sarcopenia Through Increased Oxidative Stress and Inflammation JOURNAL=British Journal of Biomedical Science VOLUME=Volume 83 - 2026 YEAR=2026 URL=https://www.frontierspartnerships.org/journals/british-journal-of-biomedical-science/articles/10.3389/bjbs.2026.15743 DOI=10.3389/bjbs.2026.15743 ISSN=2474-0896 ABSTRACT=BackgroundAgeing, a physiological process, and obesity, a pathological condition, are both associated with several metabolic alterations including energy imbalance, altered body composition, chronic low-grade inflammation, lipotoxicity, glucotoxicity, insulin resistance and mitochondrial dysfunctions. During ageing mitochondrial capacity declines and oxidative stress increases. However, the biphasic model of age-associated mitochondrial functions indicates that, before the ageing-associated decrease in mitochondrial respiration, this parameter increases in the transition from young adult to middle-aged, with a concomitant mild increase in ROS production that stimulates an antioxidant response, limiting the ageing-associated damages. Ageing-associated body composition changes can lead to sarcopenia, one of the most debilitating dysfunctions in the elderly. The sarcopenia is a known geriatric syndrome characterized by the loss of muscle mass and strength and mitochondria dysfunctions. These alterations of the disease can be exacerbated by obesity. Here, in an experimental animal model of diet-induced obesity, we evaluated the time-course changes in body composition, inflammatory and oxidative stress parameters, mitochondrial functions and antioxidant responses.MethodsMale Wistar rats at 60 days of age were divided into two experimental groups: the first group received a standard diet; the second group received a high-fat diet (HFD). The animals from both groups were fed with the appropriate diet for 1, 3, 6, 12, or 24 weeks (n = 6 for each group and time point). At each time point, the animals were sacrificed and dissected to obtain the organs and tissues needed for analysis.ResultsOur results clearly showed the contribution of high-fat diet in anticipating and worsening the metabolic and inflammatory alterations associated with age, in particular, highlighting the role of mitochondria in attempting the regulation of physiological alterations typical of aging.ConclusionIn the HFD group the antioxidant defences fail their job because of the additional inflammation and oxidative stress due to the diet. HFD is related to decreased animals’ activity. Thus, cannot be excluded that the reduced physical activity may contribute, at least in part, to the impaired mitochondrial functions in the skeletal muscle of HFD rats. Altogether, our results clearly highlighted the contribution of HFD in anticipating and worsening the metabolic and inflammatory alterations associated with aging, including sarcopenia.