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Erschienen in: Zeitschrift für Gerontologie und Geriatrie 8/2017

14.08.2017 | Themenschwerpunkt

Anabole und molekulare Interventionen am Muskel

Sinnvolle Anti-Aging-Strategie?

verfasst von: PD Dr. Thomas Münzer

Erschienen in: Zeitschrift für Gerontologie und Geriatrie | Ausgabe 8/2017

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Zusammenfassung

Die maximale Lebensspanne des Menschen beträgt rund 115 Jahre. Altern ist ein sehr individueller und komplexer Prozess, der u. a. zu „frailty“ führen kann. Altern kann nicht mit medikamentösen Maßnahmen verhindert werden, obwohl der Mythos vom Jungbrunnen immer noch existiert. Frailty geht sehr stark mit dem Verlust von Muskelmasse und -funktion einher. Darum wurden in den letzten Jahren viele Studien mit Anabolika im Sinne einer Anti-Aging-Strategie durchgeführt. Ziel solcher Interventionen war es, den altersassoziierten Verlust von Muskelmasse und Kraft zu verhindern. Die am häufigsten eingesetzten Substanzen waren Dehydroepiandrosteron (DHEA), Wachstumshormon („growth hormone“, GH) und Testosteron (T). Während sich DHEA und GH als klinisch unwirksam herausgestellt haben, scheinen die Ergebnisse von T‑Interventionen erfolgversprechender. Die Anwendung von T sollte aber nach wie vor auf Studien beschränkt bleiben. Ein neueres Zielprotein für Interventionen ist Myostatin. Dieses Protein ist ein potenter Hemmer der Muskelsynthese. Antikörper gegen Myostatin haben positive Effekte auf die Muskelmasse und die Kraft. Bisher publizierte Daten zum Einsatz von Myostatinantagonisten sind allerdings widersprüchlich. Interventionen an regulatorischen Proteinen mit Effekt auf den intramitochondrialen, den intrazellulären Stoffwechsel oder den Kalziumeinstrom haben im Tierexperiment positive Effekte auf das Muskelwachstum und die Kraft gezeigt. Bis solche Konzepte klinisch therapeutisch eingesetzt werden können, sind weitere Studien nötig.
Literatur
2.
Zurück zum Zitat Samochowiec JK, Kühne M, Frick K (2015) Digital Ageing – Unterwegs in die alterslose Gesellschaft. GDI Gottlieb Duttweiler Institute, Rüschlikon Samochowiec JK, Kühne M, Frick K (2015) Digital Ageing – Unterwegs in die alterslose Gesellschaft. GDI Gottlieb Duttweiler Institute, Rüschlikon
3.
Zurück zum Zitat Herndon JH Jr., Jiang L, Kononov T, Fox T (2015) An open label clinical trial of a multi-ingredient anti-aging moisturizer designed to improve the appearance of facial skin. J Drugs Dermatol 14(7):699–704 PubMed Herndon JH Jr., Jiang L, Kononov T, Fox T (2015) An open label clinical trial of a multi-ingredient anti-aging moisturizer designed to improve the appearance of facial skin. J Drugs Dermatol 14(7):699–704 PubMed
4.
Zurück zum Zitat Butler RN, Fossel M, Harman SM, Heward CB, Olshansky SJ, Perls TT, Rothman DJ, Rothman SM, Warner HR, West MD, Wright WE (2002) Is there an antiaging medicine? J Gerontol A Biol Sci Med Sci 57(9):B333–B338 CrossRefPubMed Butler RN, Fossel M, Harman SM, Heward CB, Olshansky SJ, Perls TT, Rothman DJ, Rothman SM, Warner HR, West MD, Wright WE (2002) Is there an antiaging medicine? J Gerontol A Biol Sci Med Sci 57(9):B333–B338 CrossRefPubMed
9.
Zurück zum Zitat Blackman MR, Sorkin JD, Münzer T, Bellantoni MF, Busby-Whitehead J, Stevens TE, Jayme J, O’Connor KG, Christmas C, Tobin JD, Stewart KJ, Cottrell E, St Clair C, Pabst KM, Harman SM (2002) Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial. JAMA 288(18):2282–2292 CrossRefPubMed Blackman MR, Sorkin JD, Münzer T, Bellantoni MF, Busby-Whitehead J, Stevens TE, Jayme J, O’Connor KG, Christmas C, Tobin JD, Stewart KJ, Cottrell E, St Clair C, Pabst KM, Harman SM (2002) Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial. JAMA 288(18):2282–2292 CrossRefPubMed
10.
Zurück zum Zitat Nair KS, Rizza RA, O’Brien P, Dhatariya K, Short KR, Nehra A, Vittone JL, Klee GG, Basu A, Basu R, Cobelli C, Toffolo G, Dalla Man C, Tindall DJ, Melton LJ 3rd, Smith GE, Khosla S, Jensen MD (2006) DHEA in elderly women and DHEA or testosterone in elderly men. N Engl J Med 355(16):1647–1659. doi: 10.​1056/​nejmoa054629 CrossRefPubMed Nair KS, Rizza RA, O’Brien P, Dhatariya K, Short KR, Nehra A, Vittone JL, Klee GG, Basu A, Basu R, Cobelli C, Toffolo G, Dalla Man C, Tindall DJ, Melton LJ 3rd, Smith GE, Khosla S, Jensen MD (2006) DHEA in elderly women and DHEA or testosterone in elderly men. N Engl J Med 355(16):1647–1659. doi: 10.​1056/​nejmoa054629 CrossRefPubMed
11.
Zurück zum Zitat Corona G, Rastrelli G, Giagulli VA, Sila A, Sforza A, Forti G, Mannucci E, Maggi M (2013) Dehydroepiandrosterone supplementation in elderly men: a meta-analysis study of lacebocontrolled trials. J Clin Endocrinol Metab 98(9):3615–3626. doi: 10.​1210/​jc.​2013-1358 CrossRefPubMed Corona G, Rastrelli G, Giagulli VA, Sila A, Sforza A, Forti G, Mannucci E, Maggi M (2013) Dehydroepiandrosterone supplementation in elderly men: a meta-analysis study of lacebocontrolled trials. J Clin Endocrinol Metab 98(9):3615–3626. doi: 10.​1210/​jc.​2013-1358 CrossRefPubMed
12.
Zurück zum Zitat Liu H, Bravata DM, Olkin I, Nayak S, Roberts B, Garber AM, Hoffman AR (2007) Systematic review: the safety and efficacy of growth hormone in the healthy elderly. Ann Intern Med 146(2):104–115 CrossRefPubMed Liu H, Bravata DM, Olkin I, Nayak S, Roberts B, Garber AM, Hoffman AR (2007) Systematic review: the safety and efficacy of growth hormone in the healthy elderly. Ann Intern Med 146(2):104–115 CrossRefPubMed
13.
Zurück zum Zitat Chu LW, Lam KS, Tam SC, Hu WJ, Hui SL, Chiu A, Chiu KC, Ng P (2001) A randomized controlled trial of low-dose recombinant human growth hormone in the treatment of malnourished elderly medical patients. J Clin Endocrinol Metab 86(5):1913–1920. doi: 10.​1210/​jcem.​86.​5.​7457 PubMed Chu LW, Lam KS, Tam SC, Hu WJ, Hui SL, Chiu A, Chiu KC, Ng P (2001) A randomized controlled trial of low-dose recombinant human growth hormone in the treatment of malnourished elderly medical patients. J Clin Endocrinol Metab 86(5):1913–1920. doi: 10.​1210/​jcem.​86.​5.​7457 PubMed
15.
Zurück zum Zitat Taaffe DR, Pruitt L, Reim J, Hintz RL, Butterfield G, Hoffman AR, Marcus R (1994) Effect of recombinant human growth hormone on the muscle strength response to resistance exercise in elderly men. J Clin Endocrinol Metab 79(5):1361–1366. doi: 10.​1210/​jcem.​79.​5.​7525633 PubMed Taaffe DR, Pruitt L, Reim J, Hintz RL, Butterfield G, Hoffman AR, Marcus R (1994) Effect of recombinant human growth hormone on the muscle strength response to resistance exercise in elderly men. J Clin Endocrinol Metab 79(5):1361–1366. doi: 10.​1210/​jcem.​79.​5.​7525633 PubMed
16.
Zurück zum Zitat Hildreth KL, Barry DW, Moreau KL, Vande Griend J, Meacham RB, Nakamura T, Wolfe P, Kohrt WM, Ruscin JM, Kittelson J, Cress ME, Ballard R, Schwartz RS (2013) Effects of testosterone and progressive resistance exercise in healthy, highly functioning older men with low-normal testosterone levels. J Clin Endocrinol Metab 98(5):1891–1900. doi: 10.​1210/​jc.​2012-3695 CrossRefPubMedPubMedCentral Hildreth KL, Barry DW, Moreau KL, Vande Griend J, Meacham RB, Nakamura T, Wolfe P, Kohrt WM, Ruscin JM, Kittelson J, Cress ME, Ballard R, Schwartz RS (2013) Effects of testosterone and progressive resistance exercise in healthy, highly functioning older men with low-normal testosterone levels. J Clin Endocrinol Metab 98(5):1891–1900. doi: 10.​1210/​jc.​2012-3695 CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Cawthon PM, Ensrud KE, Laughlin GA, Cauley JA, Dam TT, Barrett-Connor E, Fink HA, Hoffman AR, Lau E, Lane NE, Stefanick ML, Cummings SR, Orwoll ES, Osteoporotic Fractures in Men Research Group (2009) Sex hormones and frailty in older men: the osteoporotic fractures in men (MrOS) study. J Clin Endocrinol Metab 94(10):3806–3815. doi: 10.​1210/​jc.​2009-0417 CrossRefPubMedPubMedCentral Cawthon PM, Ensrud KE, Laughlin GA, Cauley JA, Dam TT, Barrett-Connor E, Fink HA, Hoffman AR, Lau E, Lane NE, Stefanick ML, Cummings SR, Orwoll ES, Osteoporotic Fractures in Men Research Group (2009) Sex hormones and frailty in older men: the osteoporotic fractures in men (MrOS) study. J Clin Endocrinol Metab 94(10):3806–3815. doi: 10.​1210/​jc.​2009-0417 CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Snyder PJ, Peachey H, Hannoush P, Berlin JA, Loh L, Lenrow DA, Holmes JH, Dlewati A, Santanna J, Rosen CJ, Strom BL (1999) Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. J Clin Endocrinol Metab 84(8):2647–2653 PubMed Snyder PJ, Peachey H, Hannoush P, Berlin JA, Loh L, Lenrow DA, Holmes JH, Dlewati A, Santanna J, Rosen CJ, Strom BL (1999) Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. J Clin Endocrinol Metab 84(8):2647–2653 PubMed
19.
Zurück zum Zitat Srinivas-Shankar U, Roberts SA, Connolly MJ, O’Connell MD, Adams JE, Oldham JA, Wu FC (2010) Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebocontrolled study. J Clin Endocrinol Metab 95(2):639–650. doi: 10.​1210/​jc.​2009-1251 CrossRefPubMed Srinivas-Shankar U, Roberts SA, Connolly MJ, O’Connell MD, Adams JE, Oldham JA, Wu FC (2010) Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebocontrolled study. J Clin Endocrinol Metab 95(2):639–650. doi: 10.​1210/​jc.​2009-1251 CrossRefPubMed
20.
Zurück zum Zitat O’Connell MD, Roberts SA, Srinivas-Shankar U, Tajar A, Connolly MJ, Adams JE, Oldham JA, Wu FC (2011) Do the effects of testosterone on muscle strength, physical function, body composition, and quality of life persist six months after treatment in intermediate-frail and frail elderly men? J Clin Endocrinol Metab 96(2):454–458. doi: 10.​1210/​jc.​2010-1167 CrossRefPubMed O’Connell MD, Roberts SA, Srinivas-Shankar U, Tajar A, Connolly MJ, Adams JE, Oldham JA, Wu FC (2011) Do the effects of testosterone on muscle strength, physical function, body composition, and quality of life persist six months after treatment in intermediate-frail and frail elderly men? J Clin Endocrinol Metab 96(2):454–458. doi: 10.​1210/​jc.​2010-1167 CrossRefPubMed
21.
Zurück zum Zitat Snyder PJ, Bhasin S, Cunningham GR, Matsumoto AM, Stephens-Shields AJ, Cauley JA, Gill TM, Barrett-Connor E, Swerdloff RS, Wang C, Ensrud KE, Lewis CE, Farrar JT, Cella D, Rosen RC, Pahor M, Crandall JP, Molitch ME, Cifelli D, Dougar D, Fluharty L, Resnick SM, Storer TW, Anton S, Basaria S, Diem SJ, Hou X, Mohler ER 3rd, Parsons JK, Wenger NK, Zeldow B, Landis JR, Ellenberg SS (2016) Effects of testosterone treatment in older men. N Engl J Med 374(7):611–624. doi: 10.​1056/​nejmoa1506119 CrossRefPubMedPubMedCentral Snyder PJ, Bhasin S, Cunningham GR, Matsumoto AM, Stephens-Shields AJ, Cauley JA, Gill TM, Barrett-Connor E, Swerdloff RS, Wang C, Ensrud KE, Lewis CE, Farrar JT, Cella D, Rosen RC, Pahor M, Crandall JP, Molitch ME, Cifelli D, Dougar D, Fluharty L, Resnick SM, Storer TW, Anton S, Basaria S, Diem SJ, Hou X, Mohler ER 3rd, Parsons JK, Wenger NK, Zeldow B, Landis JR, Ellenberg SS (2016) Effects of testosterone treatment in older men. N Engl J Med 374(7):611–624. doi: 10.​1056/​nejmoa1506119 CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Borst SE, Yarrow JF, Conover CF, Nseyo U, Meuleman JR, Lipinska JA, Braith RW, Beck DT, Martin JS, Morrow M, Roessner S, Beggs LA, McCoy SC, Cannady DF 2nd, Shuster JJ (2014) Musculoskeletal and prostate effects of combined testosterone and finasteride administration in older hypogonadal men: a randomized, controlled trial. Am J Physiol Endocrinol Metab 306(4):E433–E442. doi: 10.​1152/​ajpendo.​00592.​2013 CrossRefPubMed Borst SE, Yarrow JF, Conover CF, Nseyo U, Meuleman JR, Lipinska JA, Braith RW, Beck DT, Martin JS, Morrow M, Roessner S, Beggs LA, McCoy SC, Cannady DF 2nd, Shuster JJ (2014) Musculoskeletal and prostate effects of combined testosterone and finasteride administration in older hypogonadal men: a randomized, controlled trial. Am J Physiol Endocrinol Metab 306(4):E433–E442. doi: 10.​1152/​ajpendo.​00592.​2013 CrossRefPubMed
23.
Zurück zum Zitat Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, Eder R, Tennstedt S, Ulloor J, Zhang A, Choong K, Lakshman KM, Mazer NA, Miciek R, Krasnoff J, Elmi A, Knapp PE, Brooks B, Appleman E, Aggarwal S, Bhasin G, Hede-Brierley L, Bhatia A, Collins L, LeBrasseur N, Fiore LD, Bhasin S (2010) Adverse events associated with testosterone administration. N Engl J Med 363(2):109–122. doi: 10.​1056/​nejmoa1000485 CrossRefPubMedPubMedCentral Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, Eder R, Tennstedt S, Ulloor J, Zhang A, Choong K, Lakshman KM, Mazer NA, Miciek R, Krasnoff J, Elmi A, Knapp PE, Brooks B, Appleman E, Aggarwal S, Bhasin G, Hede-Brierley L, Bhatia A, Collins L, LeBrasseur N, Fiore LD, Bhasin S (2010) Adverse events associated with testosterone administration. N Engl J Med 363(2):109–122. doi: 10.​1056/​nejmoa1000485 CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Gormley GJ, Stoner E, Bruskewitz RC, Imperato-McGinley J, Walsh PC, McConnell JD, Andriole GL, Geller J, Bracken BR, Tenover JS et al (1992) The effect of finasteride in men with benign prostatic hyperplasia. The Finasteride Study Group. N Engl J Med 327(17):1185–1191 CrossRefPubMed Gormley GJ, Stoner E, Bruskewitz RC, Imperato-McGinley J, Walsh PC, McConnell JD, Andriole GL, Geller J, Bracken BR, Tenover JS et al (1992) The effect of finasteride in men with benign prostatic hyperplasia. The Finasteride Study Group. N Engl J Med 327(17):1185–1191 CrossRefPubMed
26.
Zurück zum Zitat Chen JL, Walton KL, Winbanks CE, Murphy KT, Thomson RE, Makanji Y, Qian H, Lynch GS, Harrison CA, Gregorevic P (2014) Elevated expression of activins promotes muscle wasting and cachexia. FASEB J 28(4):1711–1723. doi: 10.​1096/​fj.​13-245894 CrossRefPubMed Chen JL, Walton KL, Winbanks CE, Murphy KT, Thomson RE, Makanji Y, Qian H, Lynch GS, Harrison CA, Gregorevic P (2014) Elevated expression of activins promotes muscle wasting and cachexia. FASEB J 28(4):1711–1723. doi: 10.​1096/​fj.​13-245894 CrossRefPubMed
28.
Zurück zum Zitat Becker C, Lord SR, Studenski SA, Warden SJ, Fielding RA, Recknor CP, Hochberg MC, Ferrari SL, Blain H, Binder EF, Rolland Y, Poiraudeau S, Benson CT, Myers SL, Hu L, Ahmad QI, Pacuch KR, Gomez EV, Benichou O (2015) Myostatin antibody (LY2495655) in older weak fallers: a proof-of-concept, randomised, phase 2 trial. Lancet Diabetes Endocrinol 3(12):948–957. doi: 10.​1016/​s2213-8587(15)00298-3 CrossRefPubMed Becker C, Lord SR, Studenski SA, Warden SJ, Fielding RA, Recknor CP, Hochberg MC, Ferrari SL, Blain H, Binder EF, Rolland Y, Poiraudeau S, Benson CT, Myers SL, Hu L, Ahmad QI, Pacuch KR, Gomez EV, Benichou O (2015) Myostatin antibody (LY2495655) in older weak fallers: a proof-of-concept, randomised, phase 2 trial. Lancet Diabetes Endocrinol 3(12):948–957. doi: 10.​1016/​s2213-8587(15)00298-3 CrossRefPubMed
29.
Zurück zum Zitat Padhi D, Higano CS, Shore ND, Sieber P, Rasmussen E, Smith MR (2014) Pharmacological inhibition of myostatin and changes in lean body mass and lower extremity muscle size in patients receiving androgen deprivation therapy for prostate cancer. J Clin Endocrinol Metabolism 99(10):E1967–1975. doi: 10.​1210/​jc.​2014-1271 Padhi D, Higano CS, Shore ND, Sieber P, Rasmussen E, Smith MR (2014) Pharmacological inhibition of myostatin and changes in lean body mass and lower extremity muscle size in patients receiving androgen deprivation therapy for prostate cancer. J Clin Endocrinol Metabolism 99(10):E1967–1975. doi: 10.​1210/​jc.​2014-1271
30.
Zurück zum Zitat Woodhouse L, Gandhi R, Warden SJ, Poiraudeau S, Myers SL, Benson CT, Hu L, Ahmad QI, Linnemeier P, Gomez EV, Benichou O (2016) A phase 2 randomized study investigating the efficacy and safety of myostatin antibody LY2495655 versus placebo in patients undergoing elective total hip arthroplasty. J Frailty Aging 5(1):62–70. doi: 10.​14283/​jfa.​2016.​81 Woodhouse L, Gandhi R, Warden SJ, Poiraudeau S, Myers SL, Benson CT, Hu L, Ahmad QI, Linnemeier P, Gomez EV, Benichou O (2016) A phase 2 randomized study investigating the efficacy and safety of myostatin antibody LY2495655 versus placebo in patients undergoing elective total hip arthroplasty. J Frailty Aging 5(1):62–70. doi: 10.​14283/​jfa.​2016.​81
32.
Zurück zum Zitat Lee CG, Boyko EJ, Barrett-Connor E, Miljkovic I, Hoffman AR, Everson-Rose SA, Lewis CE, Cawthon PM, Strotmeyer ES, Orwoll ES (2011) Insulin sensitizers may attenuate lean mass loss in older men with diabetes. Diabetes Care 34(11):2381–2386. doi: 10.​2337/​dc11-1032 CrossRefPubMedPubMedCentral Lee CG, Boyko EJ, Barrett-Connor E, Miljkovic I, Hoffman AR, Everson-Rose SA, Lewis CE, Cawthon PM, Strotmeyer ES, Orwoll ES (2011) Insulin sensitizers may attenuate lean mass loss in older men with diabetes. Diabetes Care 34(11):2381–2386. doi: 10.​2337/​dc11-1032 CrossRefPubMedPubMedCentral
Metadaten
Titel
Anabole und molekulare Interventionen am Muskel
Sinnvolle Anti-Aging-Strategie?
verfasst von
PD Dr. Thomas Münzer
Publikationsdatum
14.08.2017
Verlag
Springer Medizin
Erschienen in
Zeitschrift für Gerontologie und Geriatrie / Ausgabe 8/2017
Print ISSN: 0948-6704
Elektronische ISSN: 1435-1269
DOI
https://doi.org/10.1007/s00391-017-1299-y