Sarcopenia is a syndrome characterized by a progressive and generalized skeletal muscle mass and strength loss, as well as a poor physical performance, which as strongly been associated with aging. Sedentary lifestyle in the elderly contributes to this condition; however, physical activity improves health, reducing morbidity and mortality. Recent studies have shown that metformin (MTF) can also prevent muscle damage promoting muscular performance. To date, there is great controversy if MTF treatment combined with exercise training improves or nullifies the benefits provided by physical activity. This study is aimed at evaluating the effect of long-term moderate exercise combined with MTF treatment on body composition, strength, redox state, and survival rate during the life of female Wistar rats. In this study, rats performed moderate exercise during 20 of their 24 months of life and were treated with MTF for one year or for 6 months, i.e., from 12 to 24 months old and 18 to 24 months old. The body composition (percentage of fat, bone, and lean mass) was determined using a dual-energy X-ray absorption scanner (DXA), and grip strength was determined using a dynamometer. Likewise, medial and tibial nerve somatosensory evoked potentials were evaluated and the redox state was measured by HPLC, calculating the GSH/GSSG ratio in the gastrocnemius muscle. Our results suggest- that the MTF administration, both in the sedentary and the exercise groups, might activate a mechanism that is directly related to the induction of the hormetic response through the redox state modulation. MTF treatment does not eliminate the beneficial effects of exercise throughout life, and although MTF does not increase muscle mass, it increases longevity.

The loss of skeletal muscle mass and strength is known as sarcopenia; it is characterized as a progressive and generalized muscle disorder associated with aging. This deterioration can seriously compromise the elderly’s health and reduce their quality of life. In addition to age, there are other factors that induce muscle mass loss, among which are sedentary lifestyle, chronic diseases, inflammation, and obesity. In recent years, a new clinical condition has been observed in older adults that affects their physical capacities and quality of life, which is known as osteosarcopenic obesity (OSO). Osteoporosis, sarcopenia, and obesity coexist in this condition. Physical exercise and nutritional management are the most widely used interventions for the treatment and prevention of sarcopenia. However, in older adults, physical exercise and protein intake do not have the same outcomes observed in younger people. Here, we used a low‐intensity exercise routine for a long period of time (LIERLT) in order to delay the OSO appearance related to sedentarism and aging in female Wistar rats. The LIERLT routine consisted of walking at 15 m/min for 30 min, five days a week for 20 months. To evaluate the effects of the LIERLT routine, body composition was determined using DXA‐scan, additionally, biochemical parameters, inflammatory profile, oxidative protein damage, redox state, and serum concentration of GDF‐11 at different ages were evaluated (4, 8, 12, 18, 22, and 24 months). Our results show that the LIERLT routine delays OSO phenotype in old 24‐month‐old rats, in a mechanism involving the decrease in the inflammatory state and oxidative stress. GDF‐11 was evaluated as a protein related to muscle repair and regeneration; interestingly, rats that perform the LIERLT increased their GDF‐11 levels.