Age-related deficit in load-induced skeletal muscle growth.

The growth response of ankle flexor and extensor muscles to two models of increased loading, functional overload (FO) and hind-limb reloading following hind-limb suspension, was measured by wet weight in Fisher 344-Brown Norway rats at ages ranging from 6 to 30 months. In response to FO, there was a 40% decrease in absolute growth of the plantaris beginning in middle age. Interestingly, the growth response to FO of 30-month old rats maintained on a 40% calorie-restricted diet improved by more than twofold relative to 30-month old rats on a normal chow diet. Recovery of muscle mass upon reloading following disuse was significantly impaired (reduced 7-16%) in predominantly fast, but not slow, muscles of 30-month relative to 9-month old rats. Initial investigation of the Akt signaling pathway following FO suggests a reduction or delay in activation of Akt and its downstream targets in response to increased loading in old rats.

[1]  K. Eguchi,et al.  Effects of Reduced Joint Mobility on Sarcomere Length, Collagen Fibril Arrangement in the Endomysium, and Hyaluronan in Rat Soleus Muscle , 2004, Journal of Muscle Research & Cell Motility.

[2]  D. Bolster,et al.  Resistance Exercise Increases Muscle Protein Synthesis and Translation of Eukaryotic Initiation Factor 2Bϵ mRNA in a Mammalian Target of Rapamycin-dependent Manner* , 2005, Journal of Biological Chemistry.

[3]  J. Faulkner,et al.  Muscle atrophy and weakness with aging: contraction-induced injury as an underlying mechanism. , 1995, The journals of gerontology. Series A, Biological sciences and medical sciences.

[4]  E. Pistilli,et al.  Molecular regulation of apoptosis in fast plantaris muscles of aged rats. , 2006, The journals of gerontology. Series A, Biological sciences and medical sciences.

[5]  R E Grindeland,et al.  Interactive effects of growth hormone and exercise on muscle mass in suspended rats. , 1994, The American journal of physiology.

[6]  K. Esser,et al.  Regulation of translation factors during hindlimb unloading and denervation of skeletal muscle in rats. , 2001, American journal of physiology. Cell physiology.

[7]  E. Ravussin,et al.  Energy restriction and aging , 2004, Current opinion in clinical nutrition and metabolic care.

[8]  H. Degens,et al.  Skeletal muscle function and hypertrophy are diminished in old age , 2003, Muscle & nerve.

[9]  M. McConkey,et al.  Caloric restriction protects mitochondrial function with aging in skeletal and cardiac muscles. , 2006, Rejuvenation research.

[10]  V R Edgerton,et al.  The plasticity of skeletal muscle: effects of neuromuscular activity. , 1991, Exercise and sport sciences reviews.

[11]  S. Dodd,et al.  Life-long calorie restriction in Fischer 344 rats attenuates age-related loss in skeletal muscle-specific force and reduces extracellular space. , 2003, Journal of applied physiology.

[12]  K. Nair,et al.  Effects of caloric restriction on mitochondrial function and gene transcripts in rat muscle. , 2002, American journal of physiology. Endocrinology and metabolism.

[13]  David J. Kosek,et al.  Efficacy of 3 days/wk resistance training on myofiber hypertrophy and myogenic mechanisms in young vs. older adults. , 2006, Journal of applied physiology.

[14]  B. Strotman,et al.  Age-related differences in apoptosis with disuse atrophy in soleus muscle. , 2005, American journal of physiology. Regulatory, integrative and comparative physiology.

[15]  F. Booth,et al.  Temporal alterations in protein signaling cascades during recovery from muscle atrophy. , 2003, American journal of physiology. Cell physiology.

[16]  S. Kimball,et al.  highlighted topics Exercise Effects on Muscle Insulin Signaling and Action Invited Review: Role of insulin in translational control of protein synthesis in skeletal muscle by amino acids or exercise , 2002 .

[17]  S. Spindler.  Calorie Restriction Enhances the Expression of Key Metabolic Enzymes Associated with Protein Renewal during Aging , 2001, Annals of the New York Academy of Sciences.

[18]  E. Spangenburg,et al.  Exercise increases SOCS‐3 expression in rat skeletal muscle: potential relationship to IL‐6 expression , 2006, The Journal of physiology.

[19]  N. LeBrasseur,et al.  Contraction-mediated mTOR, p70S6k, and ERK1/2 phosphorylation in aged skeletal muscle. , 2004, Journal of applied physiology.

[20]  S. Gordon,et al.  Impaired overload‐induced muscle growth is associated with diminished translational signalling in aged rat fast‐twitch skeletal muscle , 2006, The Journal of physiology.

[21]  B. Ulfhake,et al.  Behavioral impairments of the aging rat , 2007, Physiology & Behavior.

[22]  R. Fielding,et al.  Age-associated decrease in contraction-induced activation of downstream targets of Akt/mTor signaling in skeletal muscle. , 2006, American journal of physiology. Regulatory, integrative and comparative physiology.

[23]  J. Holloszy.  Mortality rate and longevity of food-restricted exercising male rats: a reevaluation. , 1997, Journal of applied physiology.

[24]  G. Yancopoulos,et al.  Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo , 2001, Nature Cell Biology.

[25]  R. Armstrong,et al.  Importance of satellite cells in the strength recovery after eccentric contraction-induced muscle injury. , 2003, American journal of physiology. Regulatory, integrative and comparative physiology.

[26]  F. Gorin,et al.  Prolonged recovery and reduced adaptation in aged rat muscle following eccentric exercise , 1995, Mechanisms of Ageing and Development.

[27]  S. McKiernan,et al.  Early‐onset calorie restriction conserves fiber number in aging rat skeletal muscle , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[28]  B. Hass,et al.  Growth curves and survival characteristics of the animals used in the Biomarkers of Aging Program. , 1999, The journals of gerontology. Series A, Biological sciences and medical sciences.

[29]  B. Merry.  Molecular mechanisms linking calorie restriction and longevity. , 2002, The international journal of biochemistry & cell biology.

[30]  D J Glass,et al.  Identification of Ubiquitin Ligases Required for Skeletal Muscle Atrophy , 2001, Science.

[31]  B. Strotman,et al.  Satellite cell regulation of muscle mass is altered at old age. , 2004, Journal of applied physiology.

[32]  E. Carmeli,et al.  Recovery of muscles of old rats after hindlimb immobilisation by external fixation is impaired compared with those of young rats , 2001, Experimental Gerontology.

[33]  M. Järvinen,et al.  Organization and distribution of intramuscular connective tissue in normal and immobilized skeletal muscles , 2004, Journal of Muscle Research & Cell Motility.

[34]  F. Booth,et al.  Myogenic regulatory factors during regeneration of skeletal muscle in young, adult, and old rats. , 1997, Journal of applied physiology.

[35]  R. Hepple,et al.  Long‐term caloric restriction abrogates the age‐related decline in skeletal muscle aerobic function , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[36]  C. K. Lee,et al.  Microarray profiling of gene expression in aging and its alteration by caloric restriction in mice. , 2001, The Journal of nutrition.

[37]  E. Blough,et al.  Lack of skeletal muscle hypertrophy in very aged male Fischer 344 x Brown Norway rats. , 2000, Journal of applied physiology.

[38]  S. Gordon,et al.  Diminished overload-induced hypertrophy in aged fast-twitch skeletal muscle is associated with AMPK hyperphosphorylation. , 2005, Journal of applied physiology.

[39]  D. Williamson,et al.  Immediate Response of Mammalian Target of Rapamycin (mTOR)‐Mediated Signalling Following Acute Resistance Exercise in Rat Skeletal Muscle , 2003, The Journal of physiology.

[40]  R. de Cabo,et al.  Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[41]  T. Prolla,et al.  Lessons learned from gene expression profile studies of aging and caloric restriction , 2005, Ageing Research Reviews.

[42]  J. Tidball,et al.  Expression of a muscle‐specific, nitric oxide synthase transgene prevents muscle membrane injury and reduces muscle inflammation during modified muscle use in mice , 2003, The Journal of physiology.

[43]  D. Bolster,et al.  Regulation of protein synthesis associated with skeletal muscle hypertrophy by insulin-, amino acid- and exercise-induced signalling , 2004, The Proceedings of the Nutrition Society.

[44]  F. Booth.  Regrowth of atrophied skeletal muscle in adult rats after ending immobilization. , 1978, Journal of applied physiology: respiratory, environmental and exercise physiology.

[45]  G. Barja,et al.  Minireview: the role of oxidative stress in relation to caloric restriction and longevity. , 2005, Endocrinology.

[46]  J. Faulkner,et al.  Contraction-induced injury: recovery of skeletal muscles in young and old mice. , 1990, The American journal of physiology.

[47]  F. Booth,et al.  Responsiveness of cell signaling pathways during the failed 15-day regrowth of aged skeletal muscle. , 2004, Journal of applied physiology.

[48]  J. Tidball,et al.  Macrophages promote muscle membrane repair and muscle fibre growth and regeneration during modified muscle loading in mice in vivo , 2007, The Journal of physiology.