ReviewThe biochemistry of aging muscle
Introduction
The body of knowledge accumulated in the last few decades concerning the biochemistry of aging muscle is enormous. This knowledge is being used to develop therapies to improve the physical condition of the elderly and to try and retard the age-related loss of muscle mass. A variety of intrinsic and extrinsic factors appear to be involved in the aging skeletal muscle. Changes in intrinsic factors associated with aging muscle include hormones, growth factors and systems associated with energy such as glucose or fatty acid metabolism, whereas extrinsic factors include diet, exercise, injuries, and sedentary lifestyles (Carmeli and Reznick, 1994). The external and internal causal factors involved in muscle aging are shown in Fig. 1.
Skeletal muscle wasting, common in both elderly humans and animals is often referred to as ‘sarcopenia of old age’. The term sarcopenia is defined as a loss of skeletal mass and function that occurs with advancing age (Morley et al., 2001). Sarcopenia is a generic term for the overall loss of muscle mass, strength and quality (structural composition, innervation, contractility, capillary density, fatiguability and glucose metabolism). Sarcopenia results in muscle weakness leading to an increased prevalence for falls, greater morbidity and loss of functional autonomy (Carmeli et al., 2000, Vandervoot and Symons, 2001). There have been several proposals regarding the underlying biochemical mechanisms for age-related sarcopenia (Short and Nair, 1999). These include: reduction in mediating factors involved in activation of progenitor myoblasts (Carlson, 1995, Crisona et al., 1998); decreased muscle protein synthesis (Viner et al., 1999, Nair, 2000); role of reactive oxygen species (Leeuwenburgh et al., 1998, Richmonds et al., 1999); metabolic consequences of alteration in enzyme activities, nitrogen imbalance, and impaired glucose metabolism (Johnson and Hammer, 1993, Tsao et al., 1996); imbalance between degradation and removal of ‘old’ damaged muscle proteins (Nair, 1995). Recently, the role of mitochondria in muscle degeneration and sarcopenia has been proposed (Wanagat et al., 2001).
Section snippets
Changes in levels of enzymatic activities and protein turnover (synthesis, degradation and repair capacities) in aging muscle
Aging affects the metabolic capacities of skeletal muscle, in particular there are changes in the activities of specific enzymes. Studies on aged human Vastus lateralis muscle showed declines in glycogenolytic and glycolytic enzyme activities resulting in reduced respiratory capacities (Kleine, 1976). Reduced-pyruvate carboxylase enzymatic activities associated with the citric acid cycle were also observed in aging muscle. Since the activities of pyruvate carboxylase are diminished to a greater
Changes in energy reserve systems and in mitochondrial function in aging muscle
There are three major systems making ATP available for muscle contraction:
- 1.
The most immediate system operates in the first 5–10 s of muscle contraction and it is based on the availability of creatine phosphate (CrP) and creatine phosphokinase (CPK).
- 2.
The fast anerobic/glycolytic system operates in the first 2 min of muscle contraction when oxygen supply to the muscle is still very limited and in short supply.
- 3.
The slow aerobic system begins taking over after the first 2 min and basically operates using
Ion content and regulation in aging muscle
Several mechanisms have been implicated to explain the functional decline of aged skeletal muscles. These involve changes in the excitation–contraction coupling process, changes in transient Ca2+ levels, alterations in chloride and potassium channels, and a slowing down of contraction times (Dunn and Radda, 1991, Tricarico and Camerino, 1995, Morimoto and Goto, 2000). For example, the elevated protein kinase C levels observed during aging have been associated with a reduction of chloride
Oxidative stress, free radicals and muscle aging
It has been suggested that aging could be caused by the accumulated deleterious effects of reactive oxygen species (ROS) throughout the lifespan (Harman, 1981). It is somewhat paradoxical that oxygen, the essential element for life, may also be harmful to the organism and indeed, the phenomenon is known as ‘the oxygen paradox’. Addition of a single electron to the oxygen molecule through a reduction process, easily occurring in the tissues, leads to the sequential creation of a series of
Diet, caloric restriction and gene expression
An excellent and comprehensive review was written few years ago on the subject of dietary restriction and its effects on aging and longevity (Yu, 1996). Dietary restriction (DR) provides the single most accepted modality that can intervene with aging processes (Hansen et al., 1999, Zainal et al., 2000, Gazdag et al., 2000).
It was shown in experimental studies in the 1930s that DR in rats can extend the mean lifespan by 30–50% in comparison with rats allowed to feed ad libidum (see: McCay et
Exercise and immobilization
Several studies discussed the effect of physical exercises on sarcopenia (Navarro-Arevalo et al., 1999, Porter, 2001) and on production of oxygen radicals, which is associated with a remarkably-enhanced rate of oxygen utilization. Physical exercise has been shown to increase accumulation of free radicals as a response to the need of oxygen. It is now well accepted that certain exercise regimens may play different roles in the production of oxygen free radicals and heat shock proteins (HSPs) (
Acknowledgements
This research was supported by grants from the Jan M. and Eugenia Krol Foundation, Lakewood, NJ, USA, and from the Technion—Vice-President for Research, and the S. Smernoff Gerontology Research Fund.
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