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The brain is one of the most sensitive organs damaged during aging due to its susceptibility to the aging-related oxidative stress. Hence, in this study, the sensory nerve pathway integrity and the memory were evaluated and related to the redox state, the antioxidant enzymes function, and the protein oxidative damage in the brain cortex (Cx) and the hippocampus (Hc) of young (4-month-old) and old (24-month-old) male and female Wistar rats. Evoked potentials (EP) were performed for the auditory, visual, and somatosensory pathways. In both males and females, the old rat groups’ latencies were larger in almost all waves when compared to the young same-sex animals. The novel object test was performed to evaluate memory. The superoxide dismutase and catalase antioxidant activity, as well as the protein oxidative damage, and the redox state were evaluated. Magnetic resonance (MR) imaging was used to obtain the diffusion tensor imaging, and the brain volume, while MR spectroscopy was used to obtain the brain metabolite concentrations (glutamine, glutamate, Myo-inositol, N-acetyl-aspartate, creatine) in the Cx and the Hc of young and old females. Our data suggest that, although there are limited variations regarding memory and nerve conduction velocity by sex, the differences concerning the redox status might be important to explain the dissimilar reactions during brain aging between males and females. Moreover, the increment in Myo-inositol levels in the Hc of old rats and the brain volume decrease suggest that redox state alterations might be correlated to neuroinflammation during brain aging. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11357-021-00353-x.

Osteosarcopenic obesity (OSO) has been associated with increase immobility, falls, fractures, and other dysfunctions, which could increase mortality risk during aging. However, its etiology remains unknown. Recent studies revealed that sedentarism, fat gain, and epigenetic regulators are critical in its development. One effective intervention to prevent and treat OSO is exercise. Therefore, in the present study, by keeping rats in conditions of sedentarism and others under a low-intensity exercise routine, we established an experimental model of OSO. We determined the degree of sarcopenia, obesity, and osteopenia at different ages and analyzed the miRNA expression during the lifespan using miRNA microarrays from gastrocnemius muscle. Interestingly microarrays results showed that there is a set of miRNAs that changed their expression with exercise. The pathway enrichment analysis showed that these miRNAs are strongly associated with immune regulation. Further inflammatory profiles with IL-6/IL-10 and TNF-α/IL-10 ratios showed that exercised rats presented a lower pro-inflammatory profile than sedentary rats. Also, the body fat gain in the sedentary group increased the inflammatory profile, ultimately leading to muscle dysfunction. Exercise prevented strength loss over time and maintained skeletal muscle functionality over time. Differential expression of miRNAs suggests that they might participate in this process by regulating the inflammatory response associated with aging, thus preventing the development of OSO.

Aging is a complex and detrimental process, which disrupts most organs and systems within the organisms. The nervous system is morphologically and functionally affected during normal aging, and oxidative stress has been involved in age-related damage, leading to cognitive decline and neurodegenerative processes. Sulforaphane (SFN) is a hormetin that activates the antioxidant and anti-inflammatory responses. So, we aimed to evaluate if SFN long-term treatment was able to prevent age-associated cognitive decline in adult and old female and male rats. Memory was evaluated in adult (15-month-old), and old (21-month-old) female and male Wistar rats after three months of SFN treatment. Young rats (4-month-old) were used as age controls. The antioxidant response induction, the redox state (GSH/GSSG), and oxidative damage were determined in the brain cortex (Cx) and hippocampus (Hc). Our results showed that SFN restored redox homeostasis in the Cx and Hc of adult rats, thus preventing cognitive decline in both sexes; however, the redox responses were not the same in males and females. Old rats were not able to recover their redox state as adults did, but they had a mild improvement. These results suggest that SFN mainly prevents rather than reverts neural damage; though, there might also be a range of opportunities to use hormetins like SFN, to improve redox modulation in old animals.

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.

Nutritional status, in particular overweight and obesity, as well as sedentarism and high-fat diet consumption, are important risk factors to develop chronic diseases, which have a higher impact on the elderly’s health. Therefore, these nutritional problems have become a concern to human healthspan and longevity. The fatty acids obtained thru the diet or due to fatty acid synthesis during obesity accumulate within the body generating toxicity and cell death. Fat is not only stored in adipose tissue, but it can also be stored in skeletal muscle. Palmitic acid (PA) has been reported as one of the most important saturated free fatty acids; it is associated to chronic oxidative stress and increased mitochondrial ROS production causing cell death by apoptosis. In skeletal muscle, palmitate has been associated with various pathophysiological consequences, which lead to muscle deterioration during aging and obesity. Since molecules that modify redox state have been proven to prevent cellular damage by inducing a hormetic response, the aim of this study was to evaluate if tert-butylhydroquinone (tBHQ) could activate an antioxidant hormetic response that would be able to protect L6 myoblasts from palmitate toxic effect. Our results provide evidence that tBHQ is able to protect L6 myoblasts against the toxicity induced by sodium palmitate due to a synergistic activation of different signaling pathways such as Nrf2 and NF-κB.

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.