Abstract
Sarcopenia is one of the most striking effects of age, the causes and the pathogenic mechanisms being largely unknown. Unfortunately, there is limited information on the effect of aging on muscle protein breakdown in basal conditions. The present study aimed at investigating if skeletal muscle ubiquitn mRNA levels and proteasome activities vary with age in healthy individuals. Ub mRNA levels were measured by northern blot analysis whereas proteasome activities were determined by evaluating the cleavage of specific fluorogenic substrates in the rectus abdominis muscle of 14 healthy male individuals. Patients were divided in three groups according to the age: (1) 20–30 years (N = 3); (2) 31–64 years (N = 5); (3) ≥65 years (N = 6). Quantitation of the ubiquitin mRNA levels (expressed in arbitrary units) (mean (SD) showed no differences among the three groups of age (20–30 years: 1352 ± 441; 31–64 years: 1324 ± 439; ≥65 years: 884 ± 400; P = 0.33). The correlation between age and muscle ubiquitin mRNA levels was not statistically significant (r = −0.4, P = 0.26). The three proteasome activities, chymotrypsin-like (CTL), trypsin-like (TL) and peptidyl-gutamyl-peptidase (PGP), expressed as nkatal × 10−3/mg protein, were similar in the three groups of patients stratified according to the age. There was no correlation between age with either CTL (r = 0.22, P = 0.4), PGP (r = 0.002, P = 0.9), and TL (r = 0.28, P = 0.33) activities. In conclusion, the present study shows that the skeletal muscle proteasome activities do not differ with age in healthy male individuals.
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Balagopal P, Rooyackers OE, Adey DB, Ades PA, Nair KS (1997) Effects of aging on in vivo synthesis of skeletal muscle myosin heavy-chain and sarcoplasmic protein in humans. Am J Physiol 273:E790–E800
Bardag-Gorce F, Farout L, Veyrat-Durebex C, Briand Y, Briand M (1999) Changes in 20S proteasome activity during aging of the LOU rat. Mol Biol Rep 26:89–93
Bossola M, Muscaritoli M, Costelli P, Bellantone R, Pacelli F, Busquets S, Argiles J, Lopez-Soriano FJ, Civello IM, Baccino FM, Rossi Fanelli F, Doglietto GB (2001) Increased muscle ubiquitin mRNA levels in gastric cancer patients. Am J Physiol Regul Integr Comp Physiol 280:R1518–R1523
Bossola M, Muscaritoli M, Costelli P, Grieco G, Bonelli G, Bellantone R, Doglietto GB, Rossi Fanelli F, Baccino FM (2003) Increased muscle proteasome activity correlates whit disease severity in gastric cancer patients. Ann Surg 237:384–389
Cai D, Lee KKH, Li M, Tang MK, Chan KM (2004) Ubiquitin expression is up-regulated in human and rat skeletal muscles during aging. Arch Bioch Biophys 425:42–50
Chai J, Wu Y, Sheng Z (2002) The relationship between skeletal muscle proteolysis and ubiquitin-proteasome proteolytic pathway in burned rats. Burns 28:527–533
Clavel S, Coldefy AS, Kurkdjian E, salles J, Margaritis G, Derijard B (2006) Atrophy-related ubiquitin ligases, atrogin-1 and MuRF1 are upregulated in aged rat tibialis anterioris muscle. Mech Ageing Dev 127:794–801
Costelli P, Baccino FM (2003) Mechanisms of skeletal muscle depletion in wasting syndromes: role of ATP-ubiquitin-dependent proteolysis. Curr Opin Clin Nutr Metab Care 6:407–412
Costelli P, Tullio RD, Baccino FM, Melloni E (2001) Activation of Ca (2+)-dependent proteolysis in skeletal muscle and heart in cancer cachexia. Br J Cancer 84:946–950
DeRuisseau KC, Kavazis AN, Powers SK (2005) Selective downregulation of ubiquitin conjugation cascade mRNA occurs in the senescent rat soleus muscle. Exp Gerontol 40:526–531
Edstrom E, Altun M, Hagglund M, Ulfhake B (2006) Atrogin-1/MAFbx and MurF1 are downregulated in aging-related loss of skeletal muscle. J Gerontol A Biol Sci Med Sci 61:663–674
Ferrington DA, Husom AD, Thompson L (2005) Altered proteasome structure, function, and oxidation in aged muscle. FASEB J 19:644–646
Filippatos GS, Anker SD, Kremastinos DT (2005) Pathophysiology of peripheral muscle wasting in cardiac cachexia. Curr Opin Clin Nutr Metab Care 8:49–54
Husom AD, Peters EA, Kolling EA, Fugere NA, Thompson LV, Ferrington DA (2004) Altered proteasome function and subunit composition in aged muscle. Arch Biochem Biophys 421:67–76
Kandarian SC, Stevenson EJ (2002) Molecular events in skeletal muscle during disuse atrophy. Exerc Sport Sci Rev 30:111–116
Kanehisa H, Miyatani M, Azuma K, Kuno S, Fukunaga T (2004) Influences of age and sex on abdominal muscle and subcutaneous fat thickness. Eur J Appl Physiol 91:534–537
Klaude M, Fredriksson K, Tjader I, Hammarqvist F, Ahlman B, Rooyackers O, Wernerman J 2007. Proteasome proteolytic activity in skeletal muscle is increased in patients with sepsis. Clin Sci (Lond) 112:499–506
Ottenheijm CA, Heunks LM, Li YP, Jin B, Minnaard R, van Hees HW, Dekhuijzen PN (2006) Activation of the ubiquitin-proteasome pathway in the diaphragm in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 174:997–1002
Radak Z, Naito H, Kaneko T, Kaneko T, Tahara S, Nakamoto H, Takahashi R, Cardozo-Pelaez F, Goto S (2002a) Exercise training decreases DNA damage and increases DNA repair and resistance against oxidative stress of proteins in aged rat skeletal muscle. Eur J Physiol 445:273–278
Radak Z, Takahashi R, Kumiyama A, Nakamoto H, Ohno H, Ookawara T, Goto S (2002b) Effect of aging and late onset dietary restriction on antioxidant enzymes and proteasome activities, and protein carbonylation of rat skeletal muscle and tendon. Exp Gerontol 37:1421–1428
Raj DS, Shah H, Shah VO, Ferrando A, Bankhurst A, Wolfe R, Zager PG (2003) Markers of inflammation, proteolysis, and apoptosis in ESRD. Am J Kidney Dis 42:1212–1220
Rooyackers OE, Adey DB, Ades PA, Nair KS (1996) Effect of age on in vivo rates of mitochondrial protein synthesis in human skeletal muscle. Proc Natl Acad Sci USA 93:15364–15369
Selsby JT, Judge AR, Yimlamai T, leeuwenburgh C, Dodd SL (2005) Life long calorie restriction increases heat shock proteins and proteasome activity in soleus muscles of Fisher 344 rats. Exper gerontol 40:37–42
Sreekumaran K (2005) Aging muscle. Am J Clin Nutr 81:953–963
Volpi E, Mittendorfer B, Wolfe SE, Wolfe RR (1999) Oral aminoacids stimulate muscle protein anabolism in the elderly despite higher first pass splanchnic extraction. Am J Physiol Endocrinol Metab 277:E513–E520
Volpi E, Sheffield-Moore M, Rasmussen B, Wolfe R (2001a) Basal muscle amino acid kinetics and protein synthesis in healthy young and older men. JAMA 286:1206–1212
Volpi E, Mittendorfer B, Rasmussen BB, Wolfe RR (2001b) The response of muscle protein anabolism to combined hyperaminoacidemia and glucose-induced hyperinsulinemia is impaired in the elderly. J Clin Endocrinol Metabol 85: 4481–4490
Welle S, Thornton C, Jozefowics R, Statt M (1993) Myofibrillar protein synthesis in young and old men. Am J Physiol Endocrinol Metab 264:E693–E698
Whitman SA, Wacker MJ, Richmond SR, Godard MP (2005) Contributions of the ubiquitin-proteasome pathway, apoptosis to human skeletal muscle wasting with age. Pflugers Arch 450:437–446
Yarakeshi KE, Zachwiweja J, Bier DM (1993) Acute effects of resistance exercise on muscle protein synthesis rate in young and elderly men and women. Am J Physiol 265:E210–E214
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Bossola, M., Pacelli, F., Costelli, P. et al. Proteasome activities in the rectus abdominis muscle of young and older individuals. Biogerontology 9, 261–268 (2008). https://doi.org/10.1007/s10522-008-9135-9
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DOI: https://doi.org/10.1007/s10522-008-9135-9