Age-related change in mobility: Perspectives from life course epidemiology and geroscience

Journals of Gerontology - Series A Biological Sciences and Medical Sciences

Volumn 71, Issue 9, 2016, Pages 1184-1194

  Ferrucci, Luigi ^a   Cooper, Rachel ^b   Shardell, Michelle ^a   Simonsick, Eleanor M ^a   Schrack, Jennifer A ^c   Kuh, Diana ^b  

^a NATIONAL INSTITUTE ON AGING   (United States)

^b MEDICAL RESEARCH COUNCIL   (United Kingdom)

^c JOHNS HOPKINS BLOOMBERG SCHOOL OF PUBLIC HEALTH   (United States)

Author keywords

Epidemiology; Geroscience; Life course; Mobility

Indexed keywords

AGED; AGING; COMPLICATION; DISABLED PERSON; EVIDENCE BASED MEDICINE; EXERCISE; GERIATRIC ASSESSMENT; GERIATRICS; HUMAN; ITALY; OSTEOPOROSIS; QUALITY OF LIFE; RISK ASSESSMENT; RISK FACTOR; STATISTICS AND NUMERICAL DATA; UNITED STATES; WALKING DIFFICULTY;

AGED; AGING; DISABLED PERSONS; EVIDENCE-BASED MEDICINE; EXERCISE; GERIATRIC ASSESSMENT; GERIATRICS; HUMANS; ITALY; MOBILITY LIMITATION; OSTEOPOROSIS; QUALITY OF LIFE; RISK ASSESSMENT; RISK FACTORS; UNITED STATES;

EID: 84978141019     PISSN: 10795006     EISSN: 1758535X     Source Type: Journal    
DOI: 10.1093/gerona/glw043     Document Type: Review

References (135)

1. Kennedy BK, Berger SL, Brunet A, et al. Geroscience: linking aging to chronic disease. Cell. 2014;159:709-713. doi:10.1016/j.cell.2014.10.039
2. Seals DR, Justice JN, LaRocca TJ. Physiological geroscience: targeting function to increase healthspan and achieve optimal longevity. J Physiol (Lond). 2015. doi:10.1113/jphysiol.2014.282665
3. Seals DR, Melov S. Translational geroscience: emphasizing function to achieve optimal longevity. Aging (Albany, NY). 2014;6:718-730.
4. Cooper R, Sayers A, Kuh D, Hardy R. A life course approach to physical capability. In: Kuh D, Cooper R, Hardy R, Richards M, Ben-Shlomo Y, eds. A Life Course Approach to Healthy Ageing. Oxford, UK: Oxford University Press; 2014:16-31.
5. Clouston SA, Brewster P, Kuh D, et al. The dynamic relationship between physical function and cognition in longitudinal aging cohorts. Epidemiol Rev. 2013;35:33-50. doi:10.1093/epirev/mxs004
6. Kennedy BK, Pennypacker JK. Drugs that modulate aging: the promising yet diffcult path ahead. Transl Res. 2014;163:456-465. doi:10.1016/j. trsl.2013.11.007
7. Justice JN, Cesari M, Seals DR, Shively CA, Carter CS. Comparative approaches to understanding the relation between aging and physical function. J Gerontol A Biol Sci Med Sci. 2015. doi:10.1093/gerona/glv035
8. Warner HR. NIA's Intervention Testing Program at 10 years of age. Age (Dordr). 2015;37:22. doi:10.1007/s11357-015-9761-5
9. Shock NW, Others A. Normal human aging: the Baltimore Longitudinal Study Of Aging. Eric Web site. http://eric.ed.gov/?id=ED292030. Accessed March 4, 2016.
10. Anton SD, Woods AJ, Ashizawa T, et al. Successful aging: advancing the science of physical independence in older adults. Ageing Res Rev. 2015;24(Pt B):304-327. doi:10.1016/j.arr.2015.09.005
11. 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;332:556-561. doi:10.1056/NEJM199503023320902
12. Guralnik JM, Ferrucci L, Pieper CF, et al. Lower extremity function and subsequent disability: consistency across studies, predictive models, and value of gait speed alone compared with the short physical performance battery. J Gerontol A Biol Sci Med Sci. 2000;55:M221-M231. doi:10.1093/gerona/55.4.M221
13. Cooper R, Kuh D, Hardy R; Mortality Review Group; FALCon and HALCyon Study Teams. Objectively measured physical capability levels and mortality: systematic review and meta-analysis. BMJ. 2010;341:c4467. doi:10.1136/bmj.c4467
14. Cooper R, Kuh D, Cooper C, et al.; FALCon and HALCyon Study Teams. Objective measures of physical capability and subsequent health: a systematic review. Age Ageing. 2011;40:14-23. doi:10.1093/ageing/afq117
15. Studenski S, Perera S, Patel K, et al. Gait speed and survival in older adults. JAMA. 2011;305:50-58. doi:10.1001/jama.2010.1923
16. Perera S, Patel KV, Rosano C, et al. Gait speed predicts incident disabil-ity: a pooled analysis. J Gerontol A Biol Sci Med Sci. 2016;71:63-71. doi:10.1093/gerona/glv126
17. Nybo H, Petersen HC, Gaist D, et al. Predictors of mortality in 2, 249 nonagenarians-the Danish 1905-Cohort Survey. J Am Geriatr Soc. 2003;51:1365-1373. doi:10.1046/j.1532-5415.2003.51453.x
18. Sabia S, Dumurgier J, Tavernier B, Head J, Tzourio C, Elbaz A. Change in fast walking speed preceding death: results from a prospective longitudinal cohort study. J Gerontol A Biol Sci Med Sci. 2014;69:354-362. doi:10.1093/gerona/glt114
19. Artaud F, Singh-Manoux A, Dugravot A, Tzourio C, Elbaz A. Decline in fast gait speed as a predictor of disability in older adults. J Am Geriatr Soc. 2015;63:1129-1136. doi:10.1111/jgs.13442
20. Kuh D; New Dynamics of Ageing (NDA) Preparatory Network. A life course approach to healthy aging, frailty, and capability. J Gerontol A Biol Sci Med Sci. 2007;62:717-721.
21. Kuh D, Ben-Shlomo Y, eds. A Life Course Approach to Chronic Disease Epidemiology. Oxford, UK: Oxford University Press; 2004.
22. Hanson MA, Gluckman PD. Early developmental conditioning of later health and disease: physiology or pathophysiology? Physiol Rev. 2014;94:1027-1076. doi:10.1152/physrev.00029.2013
23. Ng JW, Barrett LM, Wong A, Kuh D, Smith GD, Relton CL. The role of longitudinal cohort studies in epigenetic epidemiology: challenges and opportunities. Genome Biol. 2012;13:246. doi:10.1186/gb-2012-13-6-246
24. van den Hout A, Muniz-Terrera G, Matthews FE. Smooth random change point models. Stat Med. 2011;30:599-610. doi:10.1002/sim.4127
25. Shumway-Cook A, Guralnik JM, Phillips CL, et al. Age-associated declines in complex walking task performance: the Walking InCHIANTI toolkit. J Am Geriatr Soc. 2007;55:58-65. doi:10.1111/j.1532-5415.2006.00962.x
26. Autenrieth CS, Karrasch S, Heier M, et al. Decline in gait performance detected by an electronic walkway system in 907 older adults of the population-based KORA-Age study. Gerontology. 2013;59:165-173. doi:10.1159/000342206
27. Bellman M, Byrne O, Sege R. Developmental assessment of children. BMJ. 2013;346:e8687. doi:10.1136/bmj.e8687
28. Thelen E. Motor development. A new synthesis. Am Psychol. 1995;50:79-95. doi:10.1037/0003-066X.50.2.79
29. Beckung E, Carlsson G, Carlsdotter S, Uvebrant P. The natural history of gross motor development in children with cerebral palsy aged 1 to 15 years. Dev Med Child Neurol. 2007;49:751-756. doi:10.1111/j.1469-8749.2007.00751.x
30. Ferrucci L, Studenski S. Clinical problems of aging. In: Longo DL, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, Fauci AS, eds. Harrison's Principles of Internal Medicine. New York, NY: McGraw-Hill; 2012:570-585.
31. Maccormick RE. Possible acceleration of aging by adjuvant chemotherapy: a cause of early onset frailty? Med Hypotheses. 2006;67:212-215. doi:10.1016/j.mehy.2006.01.045
32. Juster RP, McEwen BS, Lupien SJ. Allostatic load biomarkers of chronic stress and impact on health and cognition. Neurosci Biobehav Rev. 2010;35:2-16. doi:10.1016/j.neubiorev.2009.10.002
33. Kritchevsky SB, de Cabo R. Energy-a hallmark of physical function. J Gerontol A Biol Sci Med Sci. 2015;70:1333. doi:10.1093/gerona/glv131
34. Gluckman PD, Hanson MA, Beedle AS. Early life events and their consequences for later disease: a life history and evolutionary perspective. Am J Hum Biol. 2007;19:1-19. doi:10.1002/ajhb.20590
35. Ferrucci L. The Baltimore Longitudinal Study of Aging (BLSA): a 50-year-long journey and plans for the future. J Gerontol A Biol Sci Med Sci. 2008;63:1416-1419. doi:10.1093/gerona/63.12.1416
36. Kuh D, Pierce M, Adams J, et al.; NSHD Scientifc and Data Collection Team. Cohort profile: updating the cohort profile for the MRC National Survey of Health and Development: a new clinic-based data collection for ageing research. Int J Epidemiol. 2011;40:e1-e9. doi:10.1093/ije/dyq231
37. Kuh D, Hardy R, Butterworth S, et al. Developmental origins of midlife grip strength: fndings from a birth cohort study. J Gerontol A Biol Sci Med Sci. 2006;61:702-706. doi:10.1093/gerona/61.7.702
38. Strand BH, Cooper R, Hardy R, Kuh D, Guralnik J. Lifelong socioeco-nomic position and physical performance in midlife: results from the British 1946 birth cohort. Eur J Epidemiol. 2011;26:475-483. doi:10.1007/s10654-011-9562-9
39. Birnie K, Cooper R, Martin RM, et al.; HALCyon Study Team. Child-hood socioeconomic position and objectively measured physical capability levels in adulthood: a systematic review and meta-analysis. PLoS One. 2011;6:e15564. doi:10.1371/journal.pone.0015564
40. Eriksson JG, Osmond C, Perälä MM, et al. Prenatal and childhood growth and physical performance in old age-fndings from the Helsinki Birth Cohort Study 1934-1944. Age (Dordr). 2015;37:108. doi:10.1007/s11357-015-9846-1
41. Martin HJ, Syddall HE, Dennison EM, Cooper C, Sayer AA. Physical performance and physical activity in older people: are developmental Influences important? Gerontology. 2009;55:186-193. doi:10.1159/000174823
42. Ridgway CL, Ong KK, Tammelin T, Sharp SJ, Ekelund U, Jarvelin MR. Birth size, infant weight gain, and motor development Influence adult physical performance. Med Sci Sports Exerc. 2009;41:1212-1221. doi:10.1249/MSS.0b013e31819794ab
43. Aihie Sayer A, Cooper C, Evans JR, et al. Are rates of ageing determined in utero? Age Ageing. 1998;27:579-583. doi:10.1093/ageing/27.5.579
44. Kuh D, Hardy R, Butterworth S, et al. Developmental origins of midlife physical performance: evidence from a British birth cohort. Am J Epidemiol. 2006;164:110-121. doi:10.1093/aje/kwj193
45. Rutter M. Achievements and challenges in the biology of environmental effects. Proc Natl Acad Sci USA. 2012;109(suppl 2):17149-17153. doi:10.1073/pnas.1121258109
46. Cooper R, Muniz Terrera G, Kuh D. Neurodevelopmental pathways are associated with changes in physical capability in early old age. Gerontolo-gist. 2013;53:S1.
47. Cooper R, Mishra GD, Kuh D. Physical activity across adulthood and physical performance in midlife: fndings from a British birth cohort. Am J Prev Med. 2011;41:376-384. doi:10.1016/j.amepre.2011.06.035
48. Strand BH, Mishra G, Kuh D, Guralnik JM, Patel KV. Smoking history and physical performance in midlife: results from the British 1946 birth cohort. J Gerontol A Biol Sci Med Sci. 2011;66:142-149. doi:10.1093/gerona/glq199
49. Nelson HD, Nevitt MC, Scott JC, Stone KL, Cummings SR. Smoking, alcohol, and neuromuscular and physical function of older women. Study of Osteoporotic Fractures Research Group. JAMA. 1994;272:1825-1831. doi:10.1001/jama.1994.03520230035035
50. van den Borst B, Koster A, Yu B, et al. Is age-related decline in lean mass and physical function accelerated by obstructive lung disease or smoking? Thorax. 2011;66:961-969. doi:10.1136/thoraxjnl-2011-200010
51. Patel KV, Coppin AK, Manini TM, et al. Midlife physical activity and mobility in older age: the InCHIANTI study. Am J Prev Med. 2006;31:217-224. doi:10.1016/j.amepre.2006.05.005
52. Tikkanen P, Nykänen I, Lönnroos E, Sipilä S, Sulkava R, Hartikainen S. Physical activity at age of 20-64 years and mobility and muscle strength in old age: a community-based study. J Gerontol A Biol Sci Med Sci. 2012;67:905-910. doi:10.1093/gerona/gls005
53. Stenholm S, Koster A, Valkeinen H, et al. Association of physical activity history with physical function and mortality in old age. J Gerontol A Biol Sci Med Sci. 2015. doi:10.1093/gerona/glv111
54. Pluijm SM, Visser M, Puts MT, et al. Unhealthy lifestyles during the life course: association with physical decline in late life. Aging Clin Exp Res. 2007;19:75-83.
55. Cooper R, Kuh D, Muniz-Terrera G. Combined associations of behavioral risk factors and health status with changes in physical capability over ten years of follow-up: the MRC National Survey of Health and Development.
56. Dodds RM, Syddall HE, Cooper R, et al. Grip strength across the life course: normative data from twelve British studies. PLoS One. 2014;9:e113637. doi:10.1371/journal.pone.0113637
57. Perna FM, Coa K, Troiano RP, et al. U.S. population muscular grip-strength estimates from the National Health and Nutrition Examination Survey (NHANES) 2011-2012. J Strength Cond Res. 2016;30:867-874. doi:10.1519/JSC.0000000000001104
58. Peterson M D, Krishnan C. Growth charts for muscular strength capacity with quantile regression. Am J Prev Med. 2015;49:935-938. doi:10.1016/j. amepre.2015.05.013
59. 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;61:1059-1064.
60. Maden-Wilkinson TM, Degens H, Jones DA, McPhee JS. Comparison of MRI and DXA to measure muscle size and age-related atrophy in thigh muscles. J Musculoskelet Neuronal Interact. 2013;13:320-328.
61. Moore AZ, Caturegli G, Metter EJ, et al. Difference in muscle quality over the adult life span and biological correlates in the Baltimore Longitudinal Study of Aging. J Am Geriatr Soc. 2014;62:230-236. doi:10.1111/jgs.12653
62. Hardy R, Cooper R, Aihie Sayer A, et al.; HALCyon study team. Body mass index, muscle strength and physical performance in older adults from eight cohort studies: the HALCyon programme. PLoS One. 2013;8:e56483. doi:10.1371/journal.pone.0056483
63. Houston DK, Ding J, Nicklas BJ, et al. The association between weight history and physical performance in the Health, Aging and Body Composition study. Int J Obes (Lond). 2007;31:1680-1687. doi:10.1038/sj.ijo.0803652
64. Schaap LA, Koster A, Visser M. Adiposity, muscle mass, and muscle strength in relation to functional decline in older persons. Epidemiol Rev. 2013;35:51-65. doi:10.1093/epirev/mxs006
65. Dodds R, Denison HJ, Ntani G, et al. Birth weight and muscle strength: a systematic review and meta-analysis. J Nutr Health Aging. 2012;16:609-615. doi:10.1007/s12603-012-0053-9
66. Senese LC, Almeida ND, Fath AK, Smith BT, Loucks EB. Associations between childhood socioeconomic position and adulthood obesity. Epidemiol Rev. 2009;31:21-51. doi:10.1093/epirev/mxp006
67. Bann D, Cooper R, Wills AK, Adams J, Kuh D; NSHD Scientifc and Data Collection Team. Socioeconomic position across life and body composition in early old age: fndings from a British birth cohort study. J Epidemiol Community Health. 2014;68:516-523. doi:10.1136/jech-2013-203373
68. Hurst L, Stafford M, Cooper R, Hardy R, Richards M, Kuh D. Lifetime socioeconomic inequalities in physical and cognitive aging. Am J Public Health. 2013;103:1641-1648. doi:10.2105/AJPH.2013.301240
69. Cooper R, Bann D, Wloch EG, Adams JE, Kuh D. "Skeletal muscle function defcit" in a nationally representative British birth cohort in early old age. J Gerontol A Biol Sci Med Sci. 2015;70:604-607. doi:10.1093/gerona/glu214
70. Rantanen T, Masaki K, Foley D, Izmirlian G, White L, Guralnik JM. Grip strength changes over 27 yr in Japanese-American men. J Appl Physiol. 1998;85:2047-2053.
71. Rantanen T, Guralnik JM, Foley D, et al. Midlife hand grip strength as a predictor of old age disability. JAMA. 1999;281:558-560. doi:10.1001/jama.281.6.558
72. den Ouden ME, Schuurmans MJ, Arts IE, van der Schouw YT. Physi-cal performance characteristics related to disability in older persons: a systematic review. Maturitas. 2011;69:208-219. doi:10.1016/j.maturi-tas.2011.04.008
73. Cooper R, Hardy R, Bann D, et al.; MRC National Survey of Health and Development Scientifc and Data Collection Team. Body mass index from age 15 years onwards and muscle mass, strength, and quality in early old age: fndings from the MRC National Survey of Health and Development. J Ger-ontol A Biol Sci Med Sci. 2014;69:1253-1259. doi:10.1093/gerona/glu039
74. Koster A, Ding J, Stenholm S, et al.; Health ABC study. Does the amount of fat mass predict age-related loss of lean mass, muscle strength, and muscle quality in older adults? J Gerontol A Biol Sci Med Sci. 2011;66:888-895. doi:10.1093/gerona/glr070
75. Stenholm S, Harris TB, Rantanen T, Visser M, Kritchevsky SB, Fer-rucci L. Sarcopenic obesity: defnition, cause and consequences. Curr Opin Clin Nutr Metab Care. 2008;11:693-700. doi:10.1097/MCO.0b013e328312c37d
76. Janssen I, Heymsfeld SB, Wang ZM, Ross R. Skeletal muscle mass and distribution in 468 men and women aged 18-88 y r. J Appl Physiol. 2000;89:81-88.
77. Aub JC. Clinical calorimetry. Arch Intern Med. 1917;XIX:823.
78. Black AE, Coward WA, Cole TJ, Prentice AM. Human energy expenditure in affuent societies: an analysis of 574 doubly-labelled water measurements. Eur J Clin Nutr. 1996;50:72-92.
79. Manini TM. Energy expenditure and aging. Ageing Res Rev. 2010;9:1-11. doi:10.1016/j.arr.2009.08.002
80. Fleg JL, Morrell CH, Bos AG, et al. Accelerated longitudinal decline of aerobic capacity in healthy older adults. Circulation. 2005;112:674-682. doi:10.1161/CIRCULATIONAHA.105.545459
81. Lawlor DA, Cooper AR, Bain C, et al. Associations of birth size and duration of breast feeding with cardiorespiratory ftness in childhood: fndings from the Avon Longitudinal Study of Parents and Children (ALSPAC). Eur J Epidemiol. 2008;23:411-422. doi:10.1007/s10654-008-9259-x
82. Salonen MK, Kajantie E, Osmond C, et al. Developmental origins of physical ftness: the Helsinki Birth Cohort Study. PLoS One. 2011;6:e22302. doi:10.1371/journal.pone.0022302
83. Schrack JA, Simonsick EM, Chaves PH, Ferrucci L. The role of energetic cost in the age-related slowing of gait speed. J Am Geriatr Soc. 2012;60:1811-1816. doi:10.1111/j.1532-5415.2012.04153.x
84. Schrack JA, Simonsick EM, Ferrucci L. The energetic pathway to mobility loss: an emerging new framework for longitudinal studies on aging. J Am Geriatr Soc. 2010;58(suppl 2):S329-S336. doi:10.1111/j.1532-5415.2010.02913.x
85. Schrack JA, Zipunnikov V, Simonsick EM, Studenski S, Ferrucci L. Rising energetic cost of walking predicts gait speed decline with aging. J Gerontol A Biol Sci Med Sci. 2016. doi:10.1093/gerona/glw002
86. McMillen IC, Robinson JS. Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol Rev. 2005;85:571-633. doi:10.1152/physrev.00053.2003
87. Harris A, Seckl J. Glucocorticoids, prenatal stress and the programming of disease. Horm Behav. 2011;59:279-289. doi:10.1016/j. yhbeh.2010.06.007
88. Worthman CM, Kuzara J. Life history and the early origins of health differentials. Am J Hum Biol. 2005;17:95-112. doi:10.1002/ajhb.20096
89. Mishra GD, Cooper R, Tom SE, Kuh D. Early life circumstances and their impact on menarche and menopause. Womens Health (Lond Engl). 2009;5:175-190. doi:10.2217/17455057.5.2.175
90. dos Santos Silva I, De Stavola BL, Mann V, Kuh D, Hardy R, Wadsworth ME. Prenatal factors, childhood growth trajectories and age at menarche. Int J Epidemiol. 2002;31:405-412. doi:10.1093/ije/31.2.405
91. Hsieh CC, Trichopoulos D, Katsouyanni K, Yuasa S. Age at menarche, age at menopause, height and obesity as risk factors for breast cancer: associations and interactions in an international case-control study. Int J Cancer. 1990;46:796-800.
92. Chen L, Li S, He C, Zhang C. Age at menarche and risk of gestational dia-betes mellitus: a prospective cohort study among 27, 482 women. Diabetes Care. 2016;39:469-471. doi:10.2337/dc15-2011
93. Gong TT, Wang YL, Ma XX. Age at menarche and endometrial cancer risk: a dose-response meta-analysis of prospective studies. Sci Rep. 2015;5:14051.
94. Lim SW, Ahn JH, Lee JA, Kim DH, Seo JH, Lim JS. Early menarche is associated with metabolic syndrome and insulin resistance in premenopausal Korean women. Eur J Pediatr. 2016;175:97-104. doi:10.1007/s00431-015-2604-7
95. Danese A, McEwen BS. Adverse childhood experiences, allostasis, allo-static load, and age-related disease. Physiol Behav. 2012;106:29-39. doi:10.1016/j.physbeh.2011.08.019
96. Gardner MP, Lightman S, Sayer AA, et al.; Halcyon Study Team. Dys-regulation of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages: an individual participant meta-analysis. Psychoneuroendocrinology. 2013;38:40-49. doi:10.1016/j. psyneuen.2012.04.016
97. Jones R, Hardy R, Sattar N, et al.; NSHD Scientifc and Data Collection Teams. Novel coronary heart disease risk factors at 60-64 years and life course socioeconomic position: the 1946 British birth cohort. Atherosclerosis. 2015;238:70-76. doi:10.1016/j.atherosclerosis.2014.11.011
98. Murray ET, Hardy R, Hughes A, et al. Overweight across the life course and adipokines, infammatory and endothelial markers at age 60-64 years: evidence from the 1946 birth cohort. Int J Obes (Lond). 2015;39:1010-1018. doi:10.1038/ijo.2015.19
99. Li Q, Wang S, Milot E, et al. Homeostatic dysregulation proceeds in parallel in multiple physiological systems. Aging Cell. 2015;14:1103-1112. doi:10.1111/acel.12402
100. Maggio M, Lauretani F, De Vita F, et al. Multiple hormonal dysregula-tion as determinant of low physical performance and mobility in older persons. Curr Pharm Des. 2014;20:3119-3148. doi:10.2174/13816128 113196660062
101. Morrisette-Thomas V, Cohen AA, Fülöp T, et al. Infamm-aging does not simply refect increases in pro-infammatory markers. Mech Ageing Dev. 2014;139:49-57. doi:10.1016/j.mad.2014.06.005
102. Barzilai N, Ferrucci L. Insulin resistance and aging: a cause or a protective response? J Gerontol A Biol Sci Med Sci. 2012;67:1329-1331. doi:10.1093/gerona/gls145
103. Kalyani RR, Corriere M, Ferrucci L. Age-related and disease-related mus-cle loss: the effect of diabetes, obesity, and other diseases. Lancet Diabetes Endocrinol. 2014;2:819-829. doi:10.1016/S2213-8587(14)70034-8
104. Kelley DE, He J, Menshikova EV, Ritov VB. Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes. 2002;51:2944-2950. doi:10.2337/diabetes.51.10.2944
105. 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;47:639-646. doi:10.1111/j.1532-5415.1999.tb01583.x
106. 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;50:1947-1954. doi:10.1046/j.1532-5415.2002.50605.x
107. Bandeen-Roche K, Walston JD, Huang Y, Semba RD, Ferrucci L. Measuring systemic infammatory regulation in older adults: evidence and utility. Rejuvenation Res. 2009;12:403-410. doi:10.1089/rej.2009.0883
108. Rodier F, Coppé JP, Patil CK, et al. Persistent DNA damage signalling triggers senescence-associated infammatory cytokine secretion. Nat Cell Biol. 2009;11:973-979. doi:10.1038/ncb1909
109. Semba RD, Bartali B, Zhou J, Blaum C, Ko CW, Fried LP. Low serum micronutrient concentrations predict frailty among older women living in the community. J Gerontol A Biol Sci Med Sci. 2006;61:594-599. doi:10.1093/gerona/61.6.594
110. Semba RD, Lauretani F, Ferrucci L. Carotenoids as protection against sarcopenia in older adults. Arch Biochem Biophys. 2007;458:141-145. doi:10.1016/j.abb.2006.11.025
111. Bartali B, Semba RD, Frongillo EA, et al. Low micronutrient levels as a predictor of incident disability in older women. Arch Intern Med. 2006;166:2335-2340. doi:10.1001/archinte.166.21.2335
112. Bartali B, Frongillo EA, Guralnik JM, et al. Serum micronutrient concentrations and decline in physical function among older persons. JAMA. 2008;299:308-315. doi:10.1001/jama.299.3.308
113. Walhovd KB, Fjell AM, Brown TT, et al.; Pediatric Imaging, Neuro-cognition, and Genetics Study. Long-term Influence of normal variation in neonatal characteristics on human brain development. Proc Natl Acad Sci USA. 2012;109:20089-20094. doi:10.1073/pnas. 1208180109
114. Douaud G, Groves AR, Tamnes CK, et al. A common brain network links development, aging, and vulnerability to disease. Proc Natl Acad Sci USA. 2014;111:17648-17653. doi:10.1073/pnas.1410378111
115. Gow AJ, Johnson W, Mishra G, Richards M, Kuh D, Deary IJ; HALCyon Study Team. Is age kinder to the initially more able? Yes, and no. Intelligence. 2012;40:49-59. doi:10.1016/j.intell.2011.10.007
116. Cadar D, Stephan BC, Jagger C, et al. The role of cognitive reserve on terminal decline: a cross-cohort analysis from two European studies: OCTO-Twin, Sweden, and Newcastle 85+, UK. Int J Geriatr Psychiatry. 2015. doi:10.1002/gps.4366
117. Richards M, Shipley B, Fuhrer R, Wadsworth ME. Cognitive ability in childhood and cognitive decline in mid-life: longitudinal birth cohort study. BMJ. 2004;328:552. doi:10.1136/bmj.37972.513819.EE
118. Clouston SA, Kuh D, Herd P, Elliott J, Richards M, Hofer SM. Ben-efts of educational attainment on adult fuid cognition: international evidence from three birth cohorts. Int J Epidemiol. 2012;41:1729-1736. doi:10.1093/ije/dys148
119. Richards M, Deary IJ. A life course approach to cognitive capability. In: Kuh D, Cooper R, Hardy R, Richards M, Ben-Shlomo Y, eds. A Life Course Approach to Healthy Ageing. Oxford, UK: Oxford University Press; 2014:32-46.
120. Verdú E, Ceballos D, Vilches JJ, Navarro X. Influence of aging on peripheral nerve function and regeneration. J Peripher Nerv Syst. 2000;5:191-208. doi:10.1111/j.1529-8027.2000.00026.x
121. Ward RE, Boudreau RM, Caserotti P, et al.; Health, Aging and Body Composition Study. Sensory and motor peripheral nerve function and incident mobility disability. J Am Geriatr Soc. 2014;62:2273-2279. doi:10.1111/jgs.13152
122. Lange-Maia BS, Newman AB, Cauley JA, et al.; Health, Aging and Body Composition Study. Sensorimotor peripheral nerve function and the longitudinal relationship with endurance walking in the health, aging and body composition study. Arch Phys Med Rehabil. 2016;97:45-52. doi:10.1016/j.apmr.2015.08.423
123. Deshpande N, Metter EJ, Ferrucci L. Validity of clinically derived cumulative somatosensory impairment index. Arch Phys Med Rehabil. 2010;91:226-232. doi:10.1016/j.apmr.2009. 10.006
124. Peters MJ, Joehanes R, Pilling LC, et al.; NABEC/UKBEC Consortium. The transcriptional landscape of age in human peripheral blood. Nat Commun. 2015;6:8570. doi:10.1038/ncomms9570
125. Metter EJ, Conwit R, Metter B, Pacheco T, Tobin J. The relationship of peripheral motor nerve conduction velocity to age-associated loss of grip strength. Aging (Milano). 1998;10:471-478.
126. Ferrucci L, Bandinelli S, Cavazzini C, et al. Neurological examination fndings to predict limitations in mobility and falls in older persons without a history of neurological disease. Am J Med. 2004;116:807-815. doi:10.1016/j.amjmed.2004.01.010
127. Gonzalez-Freire M, de Cabo R, Studenski SA, Ferrucci L. The neuromus-cular junction: aging at the crossroad between nerves and muscle. Front Aging Neurosci. 2014;6:208. doi:10.3389/fnagi.2014.00208
128. Rosso AL, Studenski SA, Chen WG, et al. Aging, the central nervous sys-tem, and mobility. J Gerontol A Biol Sci Med Sci. 2013;68:1379-1386. doi:10.1093/gerona/glt089
129. Brach JS, Studenski SA, Perera S, VanSwearingen JM, Newman AB. Gait variability and the risk of incident mobility disability in community-dwelling older adults. J Gerontol A Biol Sci Med Sci. 2007;62:983-988. doi:10.1093/gerona/62.9.983
130. Tabbarah M, Crimmins EM, Seeman TE. The relationship between cog-nitive and physical performance: MacArthur studies of successful aging. J Gerontol A Biol Sci Med Sci. 2002;57:M228-M235. doi:10.1093/gerona/57.4.M228
131. Rantanen T, Guralnik JM, Ferrucci L, Leveille S, Fried LP. Coimpair-ments: strength and balance as predictors of severe walking disability. J Gerontol A Biol Sci Med Sci. 1999;54:M172-M176. doi:10.1093/gerona/54.4.M172
132. Stenholm S, Shardell M, Bandinelli S, Guralnik JM, Ferrucci L. Physi-ological factors contributing to mobility loss over 9 years of follow-up-results from the InCHIANTI study. J Gerontol A Biol Sci Med Sci. 2015;70:591-597. doi:10.1093/gerona/glv004
133. Colbert LH, Visser M, Simonsick EM, et al. Physical activity, exercise, and infammatory markers in older adults: fndings from the Health, Aging and Body Composition Study. J Am Geriatr Soc. 2004;52:1098-1104. doi:10.1111/j.1532-5415.2004.52307.x
134. Bandinelli S, Pozzi M, Lauretani F, et al. Adding challenge to per-formance-based tests of walking: the Walking InCHIANTI Toolkit (WIT). Am J Phys Med Rehabil. 2006;85:986-991. doi:10.1097/01. phm.0000233210.69400.d4
135. Ferrucci L, Bandinelli S, Benvenuti E, et al. Subsystems contributing to the decline in ability to walk: bridging the gap between epidemiol-ogy and geriatric practice in the InCHIANTI study. J Am Geriatr Soc. 2000;48:1618-1625. doi:10.1111/j.1532-5415.2000.tb03873.x