“Oxidative stress” and muscle aging: influence of age, sex, fiber composition and function

Aim of this research was to study human muscle aging and the influence of oxidative stress correlated with physiological factors (age, sex, fiber composition and function) by measuring the antioxidant enzymes activities: total and mitochondrial superoxide dismutase (total and MnSOD), catalase (CAT), glutathione peroxidase(GSHPx) the levels of glutathione and glutathione disulfide (GSH and GSSG) and redox index. We also measured the lipid peroxide amount . As about age-related changes, we studied 120 samples (18-91 year-old) and we noted the presence of a correlation between age and ROS-mediated damages. Futhermore, it seems that 65 years could be the age at which ROS-dependent damage becomes crucial and begins to show up. Our data about sex-dependent changes showed how males may be potentially more vulnerable to oxidative damage than females. Study about fiber composition in old group (65-90 year-old) reported that subjects with +40% type II fibers not only have lipoperoxide levels lower but also detossifing system against superoxide anion more efficent than –40% type II fibers group. We also study aging process in muscle with different functions (“active”: characterized by rapid and coordinated changes during contraction, “inactive”: generating low levels of tension and maintaining this for a great duration). We observed that ROS-mediated oxidative mechanisms are different in “inactive” vs. “active” muscles. Basic Appl Myol 14(1): 37-44, 2004 The nature of mechanisms underlying aging is at present not well understood. Aging is a complex process involving morphologic and biochemical changes in single cells and in the whole organism. Various theories are advanced about the possible causes of aging; many of which agree and each of which is supported by scientific evidence [1], one of these focuses the attention on oxidative damage induced by reactive oxygen species (ROS) [2]. It has been suggested that aging could be caused by the accumulated deleterious effects of ROS throughout the life span [3]. ROS production is a process that stimulates several defensive enzymatic and nonenzymatic systems. However, a small quantity of ROS escapes elimination by antioxidant defenses and survives to damage proteins [4,5], lipids [6,7], nucleic acids [8,9] and carbohydrates [10]. The amount of ROS increases during aging as a result of functional decline of the mitochondria [11,12]. Multiple damage may explain the decrease in respiration rate and in the activities of different respiratory chain complexes in human skeletal muscle [13,14]. The skeletal muscles are particularly vulnerable to oxidative stress because they are constituted in postmitotic cells which are liable to accumulate oxidative damage over time and they use a large amount of oxygen. The effects of aging on skeletal muscle antioxidant systems may be quite different from those in liver, kidney, brain and heart [15]: recent evidence reported a marked enhancement in rat muscle antioxidant enzymes in old age [16]; however, few data are available on human skeletal muscle aging. There is also significant difference between sexes in aging. Rikans and coauthors [17] reported that cytosolic superoxide dismutase (CuZnSOD) and glutathione peroxidase (GSHPx) activities displayed sex-dependent variations in rat liver. In human aging there are also sex defferences: in women estrogens protect cultured neurons against lipid peroxidation induced both by FeSO4 and amyloid â– peptide [18]. Recently, it was also demonstrated the antioxidant effect of estrogens against cardiovascular diseases [19], hepatic fibrosis [20] “Oxidative stress” and muscle aging 38 At the cellular level, muscle aging determines crosssectional area decline, fiber denervation and fiber number loss, mainly of type II fibers [21,22]. Type II fibers show an age related reduction in both number and size [23]; on the other hand, type I fibers increase with aging or are little affected [24,25,26]. The combination of these findings indicates a large proportion of the agedependent loss in muscle mass as the result of the decline in type II fiber size [27]. With any reported body changes it must be considered whether neuromuscular responses are also a natural outcome of aging or simply a reflection of the agerelated decline in physical activity. In a review on muscle fiber type transitions Pette and Staron [28] suggested that age-related changes may be muscle specific. Regarding a possible heterogeneity of age-related changes in muscle and the involvement of muscles in different functions, it seems appropriate to compare the aging process in functional separate muscles [29]. In this research we analyzed human muscle aging and the influence of oxidative stress correlated with physiological factors: age, sex, fiber composition and function. We measured the superoxide anion (O2) dismutating capability (total SOD and mitochondrial SOD), hydrogen peroxide (H2O2) detossifing system: catalase (CAT) and GSHPx, the reducing capacity of cell: levels of glutathione and glutathione disulfide (GSH and GSSG) and redox index. We also measured the lipid peroxide (LPO) amount as a marker of lipids damage. Marzani et al. “Oxidative stress” and muscle aging Materials And Methods