Disability threatens the independence of many older adults and results in substantial late-life health care needs and associated expenditures. Sarcopenia, defined as loss of muscle mass and strength, plays a central role in disability. Our long-term goals are to gain insight into the processes that underlie the development of sarcopenia and disability and to identify possible strategies for interventions that reduce the ris of sarcopenia and disability. In the first two cycles of this R01, we examined the hypothesis that oxidative stress contributes to loss of muscle strength, decline in physical performance, disability, and mortality in older adults, and our findings support this paradigm. We also showed that advanced glycation end products (AGEs) and receptor for AGEs (RAGE) were independently associated with poor muscle strength, disability, and mortality. In the third cycle, we propose to examine the relationship between the "anti-aging" hormone klotho and sarcopenia in older adults. Klotho is a recently discovered hormone that plays a role in suppressing oxidative stress and is implicated in the pathogenesis of sarcopenia. We hypothesize that adults with low serum klotho levels have (1) lower skeletal muscle mass and strength and slower walking speed, and (2) greater decline of skeletal muscle mass and strength and walking speed, and (3) higher risk of mobility limitation, disability, and death. To address these hypotheses, we will study the relationship between serum klotho concentrations and the above outcomes in 2734 adults in the Health, Aging, and Body Composition (Health ABC) Study, a community-based prospective study of aging. We will measure serum klotho at baseline and examine the relationship between serum klotho and skeletal muscle mass, muscle strength, walking speed, mobility limitation, disability, and mortality over follow-up. Our propose studies will expand the knowledge of klotho into a novel area of investigation that focuses on sarcopenia and aging in community-dwelling adults.

Public Health Relevance

This project is relevant to public health as it aims to characterize the relationship between klotho, a recently discovered hormone, with decline of muscle mass, muscle strength, physical performance, disability, and mortality in older US adults.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG027012-08
Application #
8523711
Study Section
Special Emphasis Panel (ZRG1-PSE-K (04))
Program Officer
Dutta, Chhanda
Project Start
2005-09-30
Project End
2015-05-31
Budget Start
2013-09-01
Budget End
2014-05-31
Support Year
8
Fiscal Year
2013
Total Cost
$219,685
Indirect Cost
$84,077
Name
Johns Hopkins University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Zhang, Pingbo; Dufresne, Craig; Turner, Randi et al. (2015) The proteome of human retina. Proteomics 15:836-40
Semba, Richard D; Gebauer, Sarah K; Baer, David J et al. (2014) Dietary intake of advanced glycation end products did not affect endothelial function and inflammation in healthy adults in a randomized controlled trial. J Nutr 144:1037-42
Semba, Richard D; Huang, Hu; Lutty, Gerard A et al. (2014) The role of O-GlcNAc signaling in the pathogenesis of diabetic retinopathy. Proteomics Clin Appl 8:218-31
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Semba, Richard D; Cotch, Mary Frances; Gudnason, Vilmundur et al. (2014) Serum carboxymethyllysine, an advanced glycation end product, and age-related macular degeneration: the Age, Gene/Environment Susceptibility-Reykjavik Study. JAMA Ophthalmol 132:464-70
Semba, Richard D; Moghekar, Abhay R; Hu, Jason et al. (2014) Klotho in the cerebrospinal fluid of adults with and without Alzheimer's disease. Neurosci Lett 558:37-40
Semba, Richard D; Ferrucci, Luigi; Bartali, Benedetta et al. (2014) Resveratrol levels and all-cause mortality in older community-dwelling adults. JAMA Intern Med 174:1077-84
Semba, R D; Crasto, C; Strait, J et al. (2013) Elevated serum fibroblast growth factor 21 is associated with hypertension in community-dwelling adults. J Hum Hypertens 27:397-9
Semba, Richard D; Enghild, Jan J; Venkatraman, Vidya et al. (2013) The Human Eye Proteome Project: perspectives on an emerging proteome. Proteomics 13:2500-11
Deshpande, Nandini; Metter, E Jeffrey; Guralnik, Jack et al. (2013) Can failure on adaptive locomotor tasks independently predict incident mobility disability? Am J Phys Med Rehabil 92:704-9

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