Usefulness of preclinical models for assessing the efficacy of late-life interventions for sarcopenia

Journals of Gerontology - Series A Biological Sciences and Medical Sciences

Volumn 67 A, Issue 1, 2012, Pages 17-27

  Carter, Christy S ^a   Marzetti, Emanuele ^a,b   Leeuwenburgh, Christiaan ^a   Manini, Todd ^a   Foster, Thomas C ^c   Groban, Leanne ^d   Scarpace, Philip J ^c   Morgan, Drake ^a  

^a UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

^b CATHOLIC UNIVERSITY   (Italy)

^c UNIVERSITY OF FLORIDA   (United States)

^d WAKE FOREST SCHOOL OF MEDICINE   (United States)

Author keywords

Body composition; Enalapril repamycin; Physical function; Renin angiotensin system

Indexed keywords

RODENTIA;

ENALAPRIL; RAPAMYCIN;

ANIMAL; BODY COMPOSITION; CALORIC RESTRICTION; DRUG EFFECT; EXERCISE; FEMALE; HUMAN; LONGEVITY; MALE; MOUSE; MUSCLE ATROPHY; PHYSIOLOGY; RAT; REVIEW;

ANIMALS; BODY COMPOSITION; CALORIC RESTRICTION; ENALAPRIL; EXERCISE; FEMALE; HUMANS; LONGEVITY; MALE; MICE; RATS; SARCOPENIA; SIROLIMUS;

EID: 84856144408     PISSN: 10795006     EISSN: 1758535X     Source Type: Journal    
DOI: 10.1093/gerona/glr042     Document Type: Review

References (105)

1. Newman AB, Haggerty CL, Goodpaster B, et al. Strength and muscle quality in a well-functioning cohort of older adults: the Health, Aging and Body Composition Study. J Am Geriatr Soc. 2003;51(3):323-330. (Pubitemid 36348893)
2. Goodpaster BH, Carlson CL, Visser M, et al. Attenuation of skeletal muscle and strength in the elderly: the Health ABC Study. J Appl Physiol. 2001;90(6):2157-2165. (Pubitemid 32467407)
3. Goodpaster BH, Park SW, Harris TB, et al. The loss of skeletal muscle strength, mass, and quality in older adults: the health, aging and body composition study. J Gerontol A Biol Sci Med Sci. 2006;61(10):1059-1064. (Pubitemid 44727214)
4. Visser M, Langlois J, Guralnik JM, et al. High body fatness, but not low fat-free mass, predicts disability in older men and women: the Cardiovascular Health Study. Am J Clin Nutr. 1998;68(3):584-590. (Pubitemid 28402380)
5. Messier SP, Loeser RF, Miller GD, et al. Exercise and dietary weight loss in overweight and obese older adults with knee osteoarthritis: the Arthritis, Diet, and Activity Promotion Trial. Arthritis Rheum. 2004;50(5):1501-1510. (Pubitemid 38608072)
6. Miller GD, Rejeski WJ, Williamson JD, et al. The Arthritis, Diet and Activity Promotion Trial (ADAPT): design, rationale, and baseline results. Control Clin Trials. 2003;24(4):462-480. (Pubitemid 36831049)
7. Rochon J, Bales CW, Ravussin E, et al. Design and conduct of the CALERIE study: comprehensive assessment of the long-term effects of reducing intake of energy. J Gerontol A Biol Sci Med Sci. 2011;66(1):97-108.
8. Espeland MA, Gill TM, Guralnik J, et al. Designing clinical trials of interventions for mobility disability: results from the lifestyle interventions and independence for elders pilot (LIFE-P) trial. J Gerontol A Biol Sci Med Sci. 2007;62(11):1237-1243. (Pubitemid 350287612)
9. Nelson MR, Reid CM, Ames DA, et al. Feasibility of conducting a primary prevention trial of low-dose aspirin for major adverse cardiovascular events in older people in Australia: results from the ASPirin in Reducing Events in the Elderly (ASPREE) pilot study. Med J Aust. 2008;189(2):105-109.
10. Marzetti E, Privitera G, Simili V, et al. Multiple pathways to the same end: mechanisms of myonuclear apoptosis in sarcopenia of aging. Scientific World Journal. 2010;10:340-349.
11. Marzetti E, Hwang JC, Lees HA, et al. Mitochondrial death effectors: relevance to sarcopenia and disuse muscle atrophy. Biochim Biophys Acta. 2010;1800(3):235-244.
12. Hepple RT, Qin M, Nakamoto H, Goto S. Caloric restriction optimizes the proteasome pathway with aging in rat plantaris muscle: implications for sarcopenia. Am J Physiol Regul Integr Comp Physiol. 2008;295(4):R1231-1237.
13. Colman RJ, Beasley TM, Allison DB, Weindruch R. Attenuation of sarcopenia by dietary restriction in rhesus monkeys. J Gerontol A Biol Sci Med Sci. 2008;63(6):556-559.
14. Carter CS, Hofer T, Seo AY, Leeuwenburgh C. Molecular mechanisms of life-and health-span extension: role of calorie restriction and exercise intervention. Appl Physiol Nutr Metab. 2007;32(5):954-966.
15. Colman RJ, McKiernan SH, Aiken JM, Weindruch R. Muscle mass loss in Rhesus monkeys: age of onset. Exp Gerontol. 2005;40(7):573-581. (Pubitemid 41074803)
16. Rice KM, Linderman JK, Kinnard RS, Blough ER. The Fischer 344/NNiaHSd X Brown Norway/BiNia is a better model of sarcopenia than the Fischer 344/NNiaHSd: a comparative analysis of muscle mass and contractile properties in aging male rat models. Biogerontology. 2005;6(5):335-343. (Pubitemid 43193663)
17. Fisher AL. Of worms and women: sarcopenia and its role in disability and mortality. J Am Geriatr Soc. 2004;52(7):1185-1190. (Pubitemid 38869081)
18. Kim J, Kim D, Choi J, et al. Changes in lipid distribution during aging and its modulation by calorie restriction. Age. 2009;31(2):127-142.
19. Marzetti E, Lees HA, Wohlgemuth SE, Leeuwenburgh C. Sarcopenia of aging: underlying cellular mechanisms and protection by calorie restriction. Biofactors. 2009;35(1):28-35.
20. Kim JH, Kwak HB, Leeuwenburgh C, Lawler JM. Lifelong exercise and mild (8%) caloric restriction attenuate age-induced alterations in plantaris muscle morphology, oxidative stress and IGF-1 in the Fischer-344 rat. Exp Gerontol. 2008;43(4):317-329.
21. Marzetti E, Lawler JM, Hiona A, Manini T, Seo AY, Leeuwenburgh C. Modulation of age-induced apoptotic signaling and cellular remodeling by exercise and calorie restriction in skeletal muscle. Free Radic Biol Med. 2008;44(2):160-168.
22. rks Naylor AJ, Leeuwenburgh C. Sarcopenia: the role of apoptosis and modulation by caloric restriction. Exerc Sport Sci Rev. 2008;36(1):19-24.
23. Phillips T, Leeuwenburgh C. Muscle fiber specific apoptosis and TNF-alpha signaling in sarcopenia are attenuated by life-long calorie restriction. FASEB J. 2005;19(6):668-670. (Pubitemid 40471280)
24. Hepple RT, Baker DJ, Kaczor JJ, Krause DJ. Long-term caloric restriction abrogates the age-related decline in skeletal muscle aerobic function. FASEB J. 2005;19(10):1320-1322. (Pubitemid 41113736)
25. Drew B, Phaneuf S, Dirks A, et al. Effects of aging and caloric restriction on mitochondrial energy production in gastrocnemius muscle and heart. Am J Physiol Regul Integr Comp Physiol. 2003;284(2):R474-R480. (Pubitemid 36120164)
26. Lee CK, Klopp RG, Weindruch R, Prolla TA. Gene expression profile of aging and its retardation by caloric restriction. Science. 1999;285(5432):1390- 1393. (Pubitemid 29411668)
27. Sprott RL. Diet and calorie restriction. Exp Gerontol. 1997;32(1-2):205-214. (Pubitemid 27131719)
28. Holloszy JO. Exercise and food restriction in rats. J Nutr. 1992;122(3 suppl):774-777.
29. Holloszy JO, Schechtman KB. Interaction between exercise and food restriction: effects on longevity of male rats. J Appl Physiol. 1991;70(4):1529-1535.
30. Carter CS, Leeuwenburgh C, Daniels M, Foster TC. Influence of calorie restriction on measures of age-related cognitive decline: role of increased physical activity. J Gerontol A Biol Sci Med Sci. 2009;64(8):850-859.
31. Duffy PH, Feuers R, Nakamura KD, Leakey J, Hart RW. Effect of chronic caloric restriction on the synchronization of various physiological measures in old female Fischer 344 rats. Chronobiol Int. 1990;7(2):113-124. (Pubitemid 20318243)
32. Ingram DK, Weindruch R, Spangler EL, Freeman JR, Walford RL. Dietary restriction benefits learning and motor performance of aged mice. J Gerontol. 1987;42(1):78-81. (Pubitemid 17227186)
33. Olshansky SJ, Goldman DP, Zheng Y, Rowe JW. Aging in America in the twenty-first century: demographic forecasts from the MacArthur Foundation Research Network on an Aging Society. Milbank Q. 2009;87(4):842-862.
34. Rosenberg IH. Sarcopenia: origins and clinical relevance. J Nutr. 1997;127(5 suppl):990S-991S. (Pubitemid 27209486)
35. Clark BC, Manini TM. Functional consequences of sarcopenia and dynapenia in the elderly. Curr Opin Clin Nutr Metab Care. 2010;13(3):271-276.
36. Clark BC, Manini TM. Sarcopenia r/f dynapenia. J Gerontol A Biol Sci Med Sci. 2008;63(8):829-834.
37. Baumgartner RN. Body composition in healthy aging. Ann N Y Acad Sci. 2000;904:437-448. (Pubitemid 30389235)
38. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing. 2010;39(4):412-423.
39. Visser M. Towards a definition of sarcopenia-results from epidemiologic studies. J Nutr Health Aging. 2009;13(8):713-716.
40. Schwartz RS. Obesity in the elderly. In: Bray GA, ed . Handbook of Obesity; New York: Marcel Dekker, Inc.; 1998:103-114.
41. Marzetti E, Hwang JC, Lees HA, et al. Mitochondrial death effectors: relevance to sarcopenia and disuse muscle atrophy. Biochim Biophys Acta. 2009;1800(3):235-244.
42. You T, Sonntag WE, Leng X, Carter CS. Lifelong caloric restriction and interleukin-6 secretion from adipose tissue: effects on physical performance decline in aged rats. J Gerontol A Biol Sci Med Sci. 2007;62(10):1082-1087. (Pubitemid 47599417)
43. Cohen HJ, Pieper CF, Harris T, Rao KM, Currie MS. The association of plasma IL-6 levels with functional disability in community-dwelling elderly. J Gerontol Med Sci. 1997;52(4):M201-M208. (Pubitemid 27347153)
44. Ferrucci L, Harris TB, Guralnik JM, et al. Serum IL-6 level and the development of disability in older persons. J Am Geriatr Soc. 1999;47(6):639-646. (Pubitemid 29266628)
45. Phillips T, Childs AC, Dreon DM, Phinney S, Leeuwenburgh C. A dietary supplement attenuates IL-6 and CRP after eccentric exercise in untrained males. Med Sci Sports Exerc. 2003;35(12):2032-2037. (Pubitemid 37509702)
46. Ferrucci L, Penninx BW, Volpato S, et al. Change in muscle strength explains accelerated decline of physical function in older women with high interleukin-6 serum levels. J Am Geriatr Soc. 2002;50(12):1947-1954. (Pubitemid 35462439)
47. Penninx BW, Kritchevsky SB, Newman AB, et al. Inflammatory markers and incident mobility limitation in the elderly. J Am Geriatr Soc. 2004;52(7):1105-1113. (Pubitemid 38869069)
48. Goodpaster BH, Krishnaswami S, Resnick H, et al. Association between regional adipose tissue distribution and both type 2 diabetes and impaired glucose tolerance in elderly men and women. Diabetes Care. 2003;26(2):372-379. (Pubitemid 36929058)
49. Chung HY, Cesari M, Anton S, et al. Molecular inflammation: underpinnings of aging and age-related diseases. Ageing Res Rev. 2009;8(1):18-30.
50. Kalani R, Judge S, Carter C, Pahor M, Leeuwenburgh C. Effects of caloric restriction and exercise on age-related, chronic inflammation assessed by C-reactive protein and interleukin-6. J Gerontol A Biol Sci Med Sci. 2006;61(3):211-217.
51. Marzetti E, Carter CS, Wohlgemuth SE, et al. Changes in IL-15 expression and death-receptor apoptotic signaling in rat gastrocnemius muscle with aging and life-long calorie restriction. Mech Ageing Dev. 2009;130(4):272-280.
52. Cesari M, Penninx BW, Pahor M, et al. Inflammatory markers and physical performance in older persons: the InCHIANTI study. J Gerontol A Biol Sci Med Sci. 2004;59(3):242-248. (Pubitemid 38375337)
53. Cesari M, Pahor M, Bartali B, et al. Antioxidants and physical performance in elderly persons: the Invecchiare in Chianti (InCHIANTI) study. Am J Clin Nutr. 2004;79(2):289-294. (Pubitemid 41095983)
54. Kusminski CM, Shetty S, Orci L, Unger RH, Scherer PE. Diabetes and apoptosis: lipotoxicity. Apoptosis. 2009;14(12):1484-1495.
55. Turturro A, Witt WW, Lewis S, Hass BS, Lipman RD, Hart RW. Growth curves and survival characteristics of the animals used in the Biomarkers of Aging Program. J Gerontol Biol Sci. 1999;54(11):B492-B501. (Pubitemid 30017610)
56. Guralnik JM, Ferrucci L, Simonsick EM, Salive ME, Wallace RB. Lower-extremity function in persons over the age of 70 years as a predictor of subsequent disability. N Engl J Med. 1995;332(9):556-562.
57. Carter CS, Sonntag WE, Onder G, Pahor M. Physical performance and longevity in aged rats. J Gerontol Biol Sci. 2002;57(5):B193-B197. (Pubitemid 34464962)
58. Guralnik JM, Simonsick EM, Ferrucci L, et al. A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol Med Sci. 1994;49(2):M85-M94. (Pubitemid 24100267)
59. Studenski S, Perera S, Patel K, et al. Gait speed and survival in older adults. JAMA. 2011;305(1):50-58.
60. Carter CS, Cesari M, Ambrosius WT, et al. Angiotensin-converting enzyme inhibition, body composition, and physical performance in aged rats. J Gerontol A Biol Sci Med Sci. 2004;59(5):416-423. (Pubitemid 38649931)
61. Li H, Matheny M, Nicolson M, Tumer N, Scarpace PJ. Leptin gene expression increases with age independent of increasing adiposity in rats. Diabetes. 1997;46(12):2035-2039. (Pubitemid 27512092)
62. Yu BP, Masoro EJ, McMahan CA. Nutritional influences on aging of Fischer 344 rats: I. Physical, metabolic, and longevity characteristics. J Gerontol. 1985;40(6):657-670. (Pubitemid 16235349)
63. Payne AM, Dodd SL, Leeuwenburgh C. Life-long calorie restriction in Fischer 344 rats attenuates age-related loss in skeletal muscle-specific force and reduces extracellular space. J Appl Physiol. 2003;95(6):2554-2562. (Pubitemid 37445002)
64. Newman AB, Yanez D, Harris T, Duxbury A, Enright PL, Fried LP. Weight change in old age and its association with mortality. J Am Geriatr Soc. 2001;49(10):1309-1318. (Pubitemid 33015207)
65. Morley JE. Pathophysiology of weight loss in older persons. Nestle Nutr Workshop Ser Clin Perform Programme. 2005;10:167-172.
66. Wannamethee SG, Shaper AG, Lennon L. Reasons for intentional weight loss, unintentional weight loss, and mortality in older men. Arch Intern Med. 2005;165(9):1035-1040. (Pubitemid 40638125)
67. Dirks AJ, Leeuwenburgh C. Caloric restriction in humans: potential pitfalls and health concerns. Mech Ageing Dev. 2006;127(1):1-7. (Pubitemid 41713509)
68. Weindruch R, Walford RL, Fligiel S, Guthrie D. The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake. J Nutr. 1986;116(4):641-654. (Pubitemid 16066430)
69. Holloszy JO, Smith EK, Vining M, Adams S. Effect of voluntary exercise on longevity of rats. J Appl Physiol. 1985;59(3):826-831. (Pubitemid 16214146)
70. Dirks AJ, Leeuwenburgh C. Aging and lifelong calorie restriction result in adaptations of skeletal muscle apoptosis repressor, apoptosis-inducing factor, X-linked inhibitor of apoptosis, caspase-3, and caspase-12. Free Radic Biol Med. 2004;36(1):27-39. (Pubitemid 38068289)
71. Holloszy JO, Smith EK. Effects of exercise on longevity of rats. Fed Proc. 1987;46(5):1850-1853. (Pubitemid 17075930)
72. Holloszy JO. Exercise and longevity: studies on rats. J Gerontol. 1988;43(6):B149-B151. (Pubitemid 19026572)
73. Holloszy JO. Exercise increases average longevity of female rats despite increased food intake and no growth retardation. J Gerontol. 1993;48(3):B97-B100. (Pubitemid 23143645)
74. Holloszy JO. Mortality rate and longevity of food-restricted exercising male rats: a reevaluation. J Appl Physiol. 1997;82(2):399-403. (Pubitemid 27090162)
75. Shapiro A, Cheng KY, Gao Y, et al. The act of voluntary wheel running reverses dietary hyperphagia and increases leptin signaling in ventral tegmental area of aged obese rats. Gerontology. doi:10.1159/000321343.
76. Marzetti E, Groban L, Wohlgemuth SE, et al. Effects of short-term GH supplementation and treadmill exercise training on physical performance and skeletal muscle apoptosis in old rats. Am J Physiol Regul Integr Comp Physiol. 2008;294(2):R558-R567. (Pubitemid 351213762)
77. Narath E, Skalicky M, Viidik A. Voluntary and forced exercise influence the survival and body composition of ageing male rats differently. Exp Gerontol. 2001;36(10):1699-1711. (Pubitemid 32982874)
78. Judge S, Jang YM, Smith A, et al. Exercise by lifelong voluntary wheel running reduces subsarcolemmal and interfibrillar mitochondrial hydrogen peroxide production in the heart. Am J Physiol Regul Integr Comp Physiol. 2005;295(3):R773-780.
79. Betik AC, Thomas MM, Wright KJ, Riel CD, Hepple RT. Exercise training from late middle age until senescence does not attenuate the declines in skeletal muscle aerobic function. Am J Physiol Regul Integr Comp Physiol. 2009;297(3):R744-R755.
80. Ingram DK, Anson RM, de CR, et al. Development of calorie restriction mimetics as a prolongevity strategy. Ann N Y Acad Sci. 2004;1019:412-423. (Pubitemid 38951347)
81. Harrison DE, Strong R, Sharp ZD, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009;460(7253):392- 395.
82. Houde VP, Brule S, Festuccia WT, et al. Chronic rapamycin treatment causes glucose intolerance and hyperlipidemia by upregulating hepatic gluconeogenesis and impairing lipid deposition in adipose tissue. Diabetes. 2010;59(6):1338-1348.
83. Chang GR, Wu YY, Chiu YS, et al. Long-term administration of rapamycin reduces adiposity, but impairs glucose tolerance in high-fat diet-fed KK/HlJ mice. Basic Clin Pharmacol Toxicol. 2009;105(3):188-198.
84. Paturi S, Gutta AK, Katta A, et al. Effects of aging and gender on muscle mass and regulation of Akt-mTOR-p70s6k related signaling in the F344BN rat model. Mech Ageing Dev. 2010;131(3):202-209.
85. Chale-Rush A, Morris EP, Kendall TL, Brooks NE, Fielding RA. Effects of chronic overload on muscle hypertrophy and mTOR signaling in young adult and aged rats. J Gerontol A Biol Sci Med Sci. 2009;64(12):1232-1239.
86. Henriksen EJ, Jacob S. Modulation of metabolic control by angiotensin converting enzyme (ACE) inhibition. J Cell Physiol. 2003;196(1):171-179. (Pubitemid 36676455)
87. Carter CS, Onder G, Kritchevsky SB, Pahor M. Angiotensin-converting enzyme inhibition intervention in elderly persons: effects on body composition and physical performance. J Gerontol A Biol Sci Med Sci. 2005;60(11):1437-1446. (Pubitemid 41798452)
88. Onder G, Penninx BW, Balkrishnan R, et al. Relation between use of angiotensin-converting enzyme inhibitors and muscle strength and physical function in older women: an observational study. Lancet. 2002;359(9310):926-930. (Pubitemid 34246382)
89. Bahi L, Koulmann N, Sanchez H, et al. Does ACE inhibition enhance endurance performance and muscle energy metabolism in rats? J Appl Physiol. 2004;96(1):59-64. (Pubitemid 38031982)
90. Foianini KR, Steen MS, Kinnick TR, Schmit MB, Youngblood EB, Henriksen EJ. Effects of exercise training and ACE inhibition on insulin action in rat skeletal muscle. J Appl Physiol. 2000;89(2):687-694. (Pubitemid 30637119)
91. Moningka NC, Sasser JM, Croker B, Carter C, Baylis C. Protection against age-dependent renal injury in the F344xBrown Norway male rat is associated with maintained nitric oxide synthase. Mech Ageing Dev. 2010;132(1-2):1-7.
92. de Cavanagh EM, Inserra F, Ferder M, Ferder L. From mitochondria to disease: role of the renin-angiotensin system. Am J Nephrol. 2007;27(6):545-553. (Pubitemid 350014941)
93. Basso N, Cini R, Pietrelli A, Ferder L, Terragno NA, Inserra F. Protective effect of long-term angiotensin II inhibition. Am J Physiol Heart Circ Physiol. 2007;293(3):H1351-H1358. (Pubitemid 47367173)
94. de Cavanagh EM, Piotrkowski B, Basso N, et al. Enalapril and losartan attenuate mitochondrial dysfunction in aged rats. FASEB J. 2003;17(9):1096-1098.
95. de Cavanagh EM, Inserra F, Toblli J, Stella I, Fraga CG, Ferder L. Enalapril attenuates oxidative stress in diabetic rats. Hypertension. 2001;38(5):1130-1136. (Pubitemid 34252818)
96. de Cavanagh EM, Inserra F, Ferder L, Fraga CG. Enalapril and captopril enhance glutathione-dependent antioxidant defenses in mouse tissues. Am J Physiol Regul Integr Comp Physiol. 2000;278(3):R572-R577. (Pubitemid 30158114)
97. de Cavanagh EM, Ferder L, Carrasquedo F, et al. Higher levels of antioxidant defenses in enalapril-treated versus non-enalapril-treated hemodialysis patients. Am J Kidney Dis. 1999;34(3):445-455. (Pubitemid 29413616)
98. de Cavanagh EM, Fraga CG, Ferder L, Inserra F. Enalapril and captopril enhance antioxidant defenses in mouse tissues. Am J Physiol. 1997;272(2 Pt 2):R514-R518.
99. Inserra F, Romano LA, de Cavanagh EM, Ercole L, Ferder LF, Gomez RA. Renal interstitial sclerosis in aging: effects of enalapril and nifedipine. J Am Soc Nephrol. 1996;7(5):676-680. (Pubitemid 27465999)
100. de Cavanagh EM, Inserra F, Ferder L, Romano L, Ercole L, Fraga CG. Superoxide dismutase and glutathione peroxidase activities are increased by enalapril and captopril in mouse liver. FEBS Lett. 1995;361(1):22-24.
101. Ferder L, Inserra F, Romano L, Ercole L, Pszenny V. Decreased glomerulosclerosis in aging by angiotensin-converting enzyme inhibitors. J Am Soc Nephrol. 1994;5(4):1147-1152. (Pubitemid 24977094)
102. Santos EL, de Picoli Souza K, da Silva ED, et al. Long term treatment with ACE inhibitor enalapril decreases body weight gain and increases life span in rats. Biochem Pharmacol. 2009;78(8):951-958.
103. Weisinger RS, Stanley TK, Begg DP, Weisinger HS, Spark KJ, Jois M. Angiotensin converting enzyme inhibition lowers body weight and improves glucose tolerance in C57BL/6J mice maintained on a high fat diet. Physiol Behav. 2009;98(1-2):192-197.
104. Carter CS, Giovannini S, Seo DO, et al. Differential effects of enalapril and losartan on body composition and indices of muscle quality in aged male Fisher 344 Brown Norway rats. Age. doi:10.1007/s11357-010-9196-y.
105. Rae MJ, Butler RN, Campisi J, et al. The demographic and biomedical case for late-life interventions in aging. Sci Transl Med. 2010;2(40):40cm21.