Factors contributing to neuromuscular impairment and sarcopenia during aging

Drastic increase of myosin light chain MLC-2 in senescent skeletal muscle indicates fast-to-slow fibre transition in sarcopenia of old age

“…Using a combination of two-dimensional gel electrophoresis, mass spectrometry, immunoblotting and confocal microscopy, this study has clearly revealed that the expression of the slow MLC-2 isoform of myosin light chain is drastically increased in aged skeletal muscle. This finding supports the idea that muscle aging is associated with a transformation to a more aerobicoxidative metabolism in a slower twitching fibre population (Edstrom et al, 2007).…”

“…The activity level of the younger rat population was enhanced as compared to the older cohort. Both human and rat muscles share common age-related changes (Edstrom et al, 2007), making 26-month-old Wistar rat muscle a suitable model system to study age-dependent adaptations in sarcopenia (Doran et al, 2007b). Rat muscle aging is associated with fibre degeneration, altered fibre type size, changed fibre proportions, the incomplete recruitment of distinct fibre groupings and overall contractile weakness (Larsson and Edstrom, 1986;Alnaqeeb and Goldspink, 1987;Edstrom and Larsson, 1987;Larsson et al, 1991;Cutlip et al, 2007).…”

“…Muscle wasting in the elderly is probably not simply due to one specific sarcopenia-inducing gene or limitations in rates of cellular turn-around, but more likely triggered by a multi-factorial aetiology (Thompson, 2009). Striking histological alterations in aged skeletal muscles include an extensive variability in fibre diameter, an increased number of centrally located nuclei, grouped atrophying fibres and a higher frequency of longitudinal splitting (Edstrom et al, 2007). Previous studies into muscle aging have clearly documented the complexity of pathological changes (Faulkner et al, 2007), including a severe decline in contractile efficiency (Prochniewicz et al, 2007), mitochondrial abnormalities (Chabi et al, 2008), metabolic alterations (Vandervoort and Symons, 2001), a progressive decline in energy intake (Thomas, 2007), a drastically decreased regenerative capacity (Lorenzon et al, 2004), disturbed ion homeostasis (O'Connell et al, 2008a), uncoupling between neuronal excitation and muscle contraction (Delbono et al, 1995), decreased capillarisation (Degens, 1998), oxidative stress (Squier and Bigelow, 2000), a partially diminished cellular stress response (Kayani et al, 2008), impaired protein synthesis of myofibrillar components (Balagopal et al, 1997), increased apoptosis (Marzetti and Leeuwenburgh, 2006), denervationassociated atrophy (Carlson, 2004) and an altered equilibrium of growth factors and hormones important for the maintenance of proper muscle function (Lee et al, 2007).…”

DIGE analysis of rat skeletal muscle proteins using nonionic detergent phase extraction of young adult versus aged gastrocnemius tissue

“…Most physiological and histological studies of fibre aging indicate that sarcopenia is due to a multi-factorial pathology. Skeletal muscle aging is associated with a wide variety of cellular, biochemical and physiological alterations, including (i) grouped atrophying fibres, increased numbers of centrally located nuclei and variability in fibre diameter [9], (ii) metabolic alterations [43], (iii) mitochondrial disturbances and an increased susceptibility to apoptosis [44], (iv) a decreased regenerative capacity [45], (v) disturbed luminal ion binding and cycling [46], (vi) excitation-contraction uncoupling [47], (vii) oxidative stress [48], (viii) a blunted cellular stress response [49], (ix) impaired protein synthesis of myofibrillar components [50], ( (x) denervation-associated atrophy [51], (xi) an altered equilibrium of growth factors and hormones involved in fibre maintenance [52], and (xii) a severe decline in contractile efficiency [53]. Our proteomic map of alterations in protein expression in the aqueous versus detergent-extracted fractions from aged muscle agrees with the idea of complex biochemical changes in sarcopenia.…”

“…Although longitudinal studies indicate that contractile function may be preserved in single human muscle fibres [7], it has clearly been established that significant alterations occur at the whole-muscle level [8]. The age-related reduction in cross-sectional muscle area correlates relatively well with the decreased specific force of senescent muscles [9]. A variety of cross-sectional studies agree that the tissue mass of the aged musculature decreases dramatically.…”