Reasons for the degeneration of ageing skeletal muscle: a central role for IGF-1 signalling
- 675 Downloads
This paper examines two major possibilities for the striking loss of skeletal muscle mass and strength that occurs in very old animals and humans. It is concluded that muscle regeneration is not significantly impaired with age. Instead, it seems that individual myofibres undergo atrophy, with selective death of the fast type 2B myofibres, due to the combined effects of many age-related changes the main causes being: nutrition(under-nutrition and lack of vitamin D),decreased hormone levels (e.g growth hormone, testosterone), reduced physical activity, and a loss of nerves that innervate the muscles. The discussion focusses on the central role of a local muscle form of insulin-like growth factor-I (IGF-I) in muscle hypertrophy, atrophy and motor neurone loss. Reduced IGF-Isignalling is involved in muscle atrophy and results from decreased muscle exercise, reduced growth hormone and insulin levels, reduced vitamin D, and treatment with drugs like corticosteroids, dexamethasone, and cyclosporin. In addition, elevated levels of inflammatory cytokines like TNF-α and IL-6can cause muscle wasting (cachexia) although this is usually associated with disease, andTNF-α may also act (at least in part) by inhibiting IGF-I signalling. The possible clinical prevention of age-related muscle wasting (and associated motor neurone loss) by the locally acting muscle isoform of IGF-I is discussed.
Unable to display preview. Download preview PDF.
- Borasio GD, Robberecht W, Leigh PN, Emile J, Guiloff RJ, Jerusalem F, Silani V, Vos PE, Wokke JHJ and Dobbins T (1998) A placebo-controlled trial of insulin-like growth factor-I in amyotrophic lateral sclerosis. Eur ALS Neurol 51: 583-586Google Scholar
- Broussard SR, Zhou J, Venters HD, Bluthe RM, Freund GG, Johnson RS, Dantzer R and Kelley KW(2001) At the interface of environmental-immune interactions: cytokine and growth factor receptors. J Anim Sci 79 (E Suppl): E268-E284Google Scholar
- Carlson BM, Dedkov EI, Borisov AB and Faulkner JA (2001) Skeletal muscle regeneration in very old rats. J Gerontol 56A: B1-B10Google Scholar
- Carlson BM and Faulkner JA (1998) Muscle regeneration in young and old rats: effects of motor nerve transection with and without marcaine treatment. J Gerontol 53: B52-57Google Scholar
- Chapman IM, MacIntosh CG, Morley JE and Horowitz M (2002) The anorexia of ageing. Biogerontology 3: 67-71 (this issue) Cleveland DW (1999) From Charcot to SOD1: Mechanisms of selective motor neuron death in ALS. Neuron 24: 515-520Google Scholar
- Faulkner JA, Brooks SV and Zerba E (1995) Muscle atrophy and weakness with aging: contraction-induced injury as an underlying mechanism. J Gerontol 50A: 124-129Google Scholar
- Gayan-Ramirez G, Vanderhoydonc F, Verhoeven G and Decramer M (1999) Acute treatment with corticosteroids decreases IGF-1 and IGF-2 expression in the rat diaphragm and gastrocnemius. Am J Respir Critical Care Med 159: 283-289Google Scholar
- Gonzalez-Cadavid NF, Taylor WE, Yarasheski K, Sinha-Hikim I, Ma K, Ezzat S, Shen R, Lalani R, Asa S, Mamita M, Nair G, Arver S and Bhasin S (1998) Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting. Proce Natl Acad Sci USA 95: 14938-14943CrossRefGoogle Scholar
- Grounds MD (1991) Towards understanding skeletal muscle regeneration. Pathol Res Practice 187: 1-22Google Scholar
- Ravaglia G, Forti P, Maioli F, Nesi B, Pratelli L, Cucinotta D, Bastagli L and Cavelli G (2000) Body composition, Sex steroids, IGF-I, and bone-mineral status in aging men. J Gerontol Med Sci 55A: M516-M521Google Scholar
- Sjogren K, Liu JL, Blad K, Skrtic S, Vidal O, Wallenius V, LeRoith D, Tornell J, Isaksson OG, Jansson JO and Ohlsson C (1999) Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice. Proc Natl Acad Sci USA 96: 7088-7092PubMedCrossRefGoogle Scholar
- Tawa NEJ and Goldberg AL (1994) Protein and Amino Acid Metabolism in Muscle. In: Engel AG and Franzini-Armstrong G (eds) Myology (2nd Edition), Vol 1, pp 683-707. McGraw Hill, New YorkGoogle Scholar