Drug discovery and development for ageing: Opportunities and challenges

Philosophical Transactions of the Royal Society B: Biological Sciences

Volumn 366, Issue 1561, 2011, Pages 113-119

  Evans, William J ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

Elderly; Functional capacity; Geriatrics; Sarcopaenia

Indexed keywords

AGE STRUCTURE; AGING; DRUG; ELDERLY POPULATION; ETIOLOGY; HOSPITAL SECTOR;

EID: 79251511542     PISSN: 09628436     EISSN: 14712970     Source Type: Journal    
DOI: 10.1098/rstb.2010.0287     Document Type: Review

References (49)

1. Tzankoff, S. P. & Norris, A. H. 1978 Longitudinal changes in basal metabolic rate in man. J Appl Physiol. 33, 536-539.
2. Falzone Jr, J. A. & Shock, N.W. 1956 Physiological limitations and age. Public Health Rep. 71, 1185-1193.
3. Brandfonbrener, M., Landowne, M. & Shock, N. W. 1955 Changes in cardiac output with age. Circulation 12, 557-566.
4. Morley, J. E. 2003 Anorexia and weight loss in older persons. J. Gerontol. A Biol. Sci. Med. Sci. 58, M131-M137. (doi:10.1093/gerona/58.2.M131)
5. Thomas, D. R., Verdery, R. B., Gardner, L., Kant, A. & Lindsay, J. 1991 A prospective study of outcome from protein-energy malnutrition in nursing home residents. J. Parenter. Enter. Nutr. 15, 400-404. (doi:10.1177/ 0148607191015004400)
6. Thomas, D. R., Ashmen, W., Morley, J. E. & Evans, W. J. 2000 Nutritional management in long-term care: Development of a clinical guideline. J. Gerontol. Med. Sci. 55A, M725-M734. (doi:10.1093/gerona/55.12.M725)
7. Morley, J. E. 2002 Orexigenic and anabolic agents. Clin. Geriatr. Med. 18, 853-866. (doi:10.1016/S0749-0690 (02)00036-8)
8. Evans, W. J. 2007 Editorial: Megestrol acetate use for weight gain should be carefully considered. J. Clin. Endocrinol. Metabol. 92, 420-421. (doi:10.1210/jc. 2006-2734)
9. Fried, L. P. et al. 2001 Frailty in older adults: Evidence for a phenotype. J. Gerontol. A Biol. Sci. Med. Sci. 56, M146-M157. (doi:10.1093/gerona/56.3.M146)
10. Fried, L. P., Ferrucci, L., Darer, J., Williamson, J. D. & Anderson, G. 2004 Untangling the concepts of disability, frailty, and comorbidity: Implications for improved targeting and care. J. Gerontol. A Biol. Sci. Med. Sci. 59, M255-M263. (doi:10.1093/gerona/56.3.M255)
11. Walston, J. 2004 Frailty-the search for underlying causes. Sci. Aging Knowl. Environ. 2004, e4. (doi:10. 1126/sageke.2004.4.pe4)
12. Cesari, M., Leeuwenburgh, C., Lauretani, F., Onder, G., Bandinelli, S., Maraldi, C., Guralnik, J. M., Pahor, M. & Ferrucci, L. 2006 Frailty syndrome and skeletal muscle: Results from the Invecchiare in Chianti study. Am. J. Clin. Nutr. 83, 1142-1148.
13. Bartali, B., Frongillo, E. A., Bandinelli, S., Lauretani, F., Semba,R.D., Fried,L. P.&Ferrucci, L.2006Lownutrient intake is an essential component of frailty in older persons. J.Gerontol. A Biol. Sci. Med. Sci. 61, 589-593.
14. Leng, S., Chaves, P., Koenig, K. & Walston, J. 2002 Serum interleukin-6 and hemoglobin as physiological correlates in the geriatric syndrome of frailty: A pilot study. J. Am. Geriatr. Soc. 50, 1268-1271. (doi:10. 1046/j.1532-5415.2002.50315.x)
15. Montero-Odasso, M. & Duque, G. 2005 Vitamin D in the aging musculoskeletal system: An authentic strength preserving hormone. Mol. Aspects Med. 26, 203-219.
16. Morley, J. E., Kim, M. J. & Haren, M. T. 2005 Frailty and hormones. Rev. Endocr. Metab. Disord. 6, 101-108. (doi:10.1007/s11154-005-6722-9)
17. Evans,W. 1995 What is sarcopenia? J. Gerontol. 50A, 5-8.
18. Janssen, I., Heymsfield, S. B. & Ross, R. 2002 Low relative skeletal muscle mass (sarcopenia) in older persons is associated with functional impairment and physical disability. J. Am. Geriatr. Soc. 50, 889-896. (doi:10.1046/ j.1532-5415.2002.50216.x)
19. Walsh, M. C., Hunter, G. R. & Livingstone, M. B. 2006 Sarcopenia in premenopausal and postmenopausal women with osteopenia, osteoporosis and normal bone mineral density. Osteoporosis Int. 17, 61-67. (doi:10. 1007/s00198-005- 1900-x)
20. Ferrucci, L., Russo, C. R., Lauretani, F., Bandinelli, S. & Guralnik, J. M. 2002 A role for sarcopenia in late-life osteoporosis. Aging Clin. Exp. Res. 14, 1-4.
21. Lebrun, C. E., van der Schouw, Y. T., de Jong, F. H., Grobbee, D. E. & Lamberts, S. W. 2006 Fat mass rather than muscle strength is the major determinant of physical function and disability in postmenopausal women younger than 75 years of age. Menopause 13, 474-481. (doi:10.1097/01.gme.0000222331. 23478.ec)
22. Newman,A.B.,Kupelian,V.,Visser,M., Simonsick,E.M., Goodpaster, B. H., Kritchevsky, S. B., Tylavsky, F. A., Rubin, S. M. & Harris, T. B. 2006 Strength, but not muscle mass, is associated with mortality in the health, aging and body composition study cohort. J. Gerontol. A Biol. Sci.Med. Sci. 61, 72-77.
23. Sowers, M. R., Crutchfield, M., Richards, K., Wilkin, M. K., Furniss, A., Jannausch, M., Zhang, D. & Gross, M. 2005 Sarcopenia is related to physical functioning and leg strength in middle-aged women. J. Gerontol. A Biol. Sci. Med. Sci. 60, 486-490.
24. Campbell,W.W., Trappe, T. A.,Wolfe,R.R.&Evans,W. J. 2001 The recommended dietary allowance for protein may not be adequate for older people to maintain skeletal muscle. J. Gerontol. A Biol. Sci. Med. Sci. 56, M373-M380.
25. Visser, M., Deeg, D. J. & Lips, P. 2003 Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): The longitudinal aging study Amsterdam. J. Clin. Endocrinol. Metab. 88, 5766-5772. (doi:10.1210/jc. 2003-030604)
26. Hughes, V. A., Frontera, W. R., Roubenoff, R., Evans, W. J. & Singh, M. A. 2002 Longitudinal changes in body composition in older men and women: Role of body weight change and physical activity. Am. J. Clin. Nutr. 76, 473-481.
27. Schaap, L. A., Pluijm, S. M., Deeg, D. J. & Visser, M. 2006 Inflammatory markers and loss of muscle mass (sarcopenia) and strength. Am. J. Med. 119, e9-e17. (doi:10.1016/j.amjmed.2005.10.049)
28. Park, S. W., Goodpaster, B. H., Strotmeyer, E. S., de Rekeneire, N., Harris, T. B., Schwartz, A. V., Tylavsky, F. A. & Newman, A. B. 2006 Decreased muscle strength and quality in older adults with type 2 diabetes: The health, aging, and body composition study. Diabetes 55, 1813-1818. (doi:10.2337/db05- 1183)
29. Park, S. W. et al. 2009 Excessive loss of skeletal muscle mass in older adults with type 2 diabetes. Diabetes Care 32, 2136-2137. (doi:10.2337/dc09- 0264)
30. Baumgartner, R. N., Koehler, K. M., Gallagher, D., Romero, L., Heymsfield, S. B., Ross, R. R., Garry, P. J. & Lindeman, R. D. 1998 Epidemiology of sarcopenia among the elderly in NewMexico. Am. J. Epidemiol. 147, 755-763.
31. Iannuzzi-Sucich, M., Prestwood, K. M. & Kenny, A. M. 2002 Prevalence of sarcopenia and predictors of skeletal muscle mass in healthy, older men and women. J. Gerontol. A Biol. Sci. Med. Sci. 57, M772-M777.
32. Janssen, I., Shepard, D. S., Katzmarzyk, P. T. & Roubenoff, R. 2004 The healthcare costs of sarcopenia in the United States. J. Am. Geriatr. Soc. 52, 80-85. (doi:10.1111/j.1532-5415.2004.52014.x)
33. Bhasin, S. et al. 2005 Older men are as responsive as young men to the anabolic effects of graded doses of testosterone on the skeletal muscle. J. Clin. Endocrinol. Metab. 90, 678-688. (doi:10.1210/jc.2004-1184)
34. Frontera, W. R., Meredith, C. N., O'Reilly, K. P., Knuttgen, H. G. & Evans, W. J. 1988 Strength conditioning in older men: Skeletal muscle hypertrophy and improved function. J. Appl. Physiol. 64, 1038-1044.
35. Fiatarone, M. A. et al. 1994 Exercise training and nutritional supplementation for physical frailty in very elderly people. N. Engl. J. Med. 330, 1769-1775. (doi:10.1056/ NEJM199406233302501)
36. Baumgartner, R.N.,Wayne, S. J.,Waters,D. L., Janssen, I., Gallagher, D. & Morley, J. E. 2004 Sarcopenic obesity predicts instrumental activities of daily living disability in the elderly. Obes. Res. 12, 1995-2004. (doi:10.1038/oby. 2004.250)
37. Zoico, E., Di Francesco, V., Guralnik, J. M., Mazzali, G., Bortolani, A., Guariento, S., Sergi, G., Bosello, O. & Zamboni, M. 2004 Physical disability and muscular strength in relation to obesity and different body composition indexes in a sample of healthy elderly women. Int. J. Obes. Relat. Metab. Disord. 28, 234-241.
38. Goodpaster, B. H., Carlson, C. L., Visser, M., Kelley, D. E., Scherzinger, A., Harris, T. B., Stamm, E. & Newman, A. B. 2001 Attenuation of skeletal muscle and strength in the elderly: The Health ABC study. J. Appl. Physiol. 90, 2157-2165.
39. Goodpaster, B. H. & Brown, N. F. 2005 Skeletal muscle lipid and its association with insulin resistance: What is the role for exercise? Exerc. Sport Sci. Rev. 33, 150-154. (doi:10.1097/00003677-200507000-00008)
40. Miller, S. L. & Wolfe, R. R. 2008 The danger of weight loss in the elderly. J. Nutr. Health Aging 12, 487-491. (doi:10.1007/BF02982710)
41. Ensrud, K. E., Ewing, S. K., Stone, K. L., Cauley, J. A., Bowman, P. J. & Cummings, S. R. 2003 Intentional and unintentional weight loss increase bone loss and hip fracture risk in older women. J. Am. Geriatr. Soc. 51, 1740-1747.
42. Bhasin, S. et al. 2008 Functional outcomes for clinical trials in frail older persons: Time to be moving. J. Gerontol. A Biol. Sci. Med. Sci. 63, 160-164.
43. Harper, C. M. & Lyles, Y. M. 1988 Physiology and complications of bed rest. J. Am. Geriatr. Soc. 36, 1047-1054.
44. Convinsky, K. E., Palmer, R. M., Fortinsky, R. H., Counsel, S. R., Stewart, A. L., Kresevic, D., Burant, D. & Landefeld, C. S. 2003 Loss of independence in activities of daily living in older adults hospitalized with medical illnesses: Increased vulnerability with age. J. Am. Geriatr. Soc. 51, 451-458.
45. Anonymous. 2003 HCUPnet, healthcare cost and utilization project. Rockville, MD: Agency for Healthcare Research and Quality. See http://www.ahrq.gov/data/ acup/hcupnet.htm.
46. Kortebein, P., Ferrando, A., Lombeida, J., Wolfe, R. & Evans,W. J. 2007 Effect of 10 days of bed rest on skeletal muscle in healthy older adults. JAMA 297, 1772-1774. (doi:10.1001/jama.297.16.1772-b)
47. Kortebein, P. et al. 2008 Functional impact of 10 days of bed rest in healthy older adults. J. Gerontol. A Biol. Sci. Med. Sci. 63, 1076-1081.
48. Sullivan, D. H., Sun, S. & Walls, R. C. 1999 Proteinenergy undernutrition among elderly hospitalized patients: A prospective study. JAMA 281, 2013-2019. (doi:10.1001/jama.281.21.2013)
49. Guralnik, J. M., Ferrucci, L., Simonsick, E. M., Salive, M. E. & Wallace, R. B. 1995 Lower-extremity function in persons over the age of 70 years as a predictor of subsequent disability. N. Engl. J. Med. 332, 556-561. (doi:10.1056/NEJM199503023320902)