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.
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.
|Zhu, Min; Zhang, Pingbo; Geng-Spyropoulos, Minghui et al. (2016) A robotic protocol for high-throughput processing of samples for selected reaction monitoring assays. Proteomics :|
|Zhang, Pingbo; Zhu, Min; Geng-Spyropoulos, Minghui et al. (2016) A novel, multiplexed targeted mass spectrometry assay for quantification of complement factor H (CFH) variants and CFH-related proteins 1-5 in human plasma. Proteomics :|
|Hileman, Corrilynn O; Turner, Randi; Funderburg, Nicholas T et al. (2016) Changes in oxidized lipids drive the improvement in monocyte activation and vascular disease after statin therapy in HIV. AIDS 30:65-73|
|Semba, Richard D; Ferrucci, Luigi; Sun, Kai et al. (2016) Low Plasma Klotho Concentrations and Decline of Knee Strength in Older Adults. J Gerontol A Biol Sci Med Sci 71:103-8|
|Semba, Richard D; Shardell, Michelle; Trehan, Indi et al. (2016) Metabolic alterations in children with environmental enteric dysfunction. Sci Rep 6:28009|
|Moaddel, Ruin; Fabbri, Elisa; Khadeer, Mohammed A et al. (2016) Plasma Biomarkers of Poor Muscle Quality in Older Men and Women from the Baltimore Longitudinal Study of Aging. J Gerontol A Biol Sci Med Sci 71:1266-72|
|Semba, Richard D; Shardell, Michelle; Sakr Ashour, Fayrouz A et al. (2016) Child Stunting is Associated with Low Circulating Essential Amino Acids. EBioMedicine 6:246-52|
|Semba, Richard D; Gonzalez-Freire, Marta; Moaddel, Ruin et al. (2016) Environmental Enteric Dysfunction is Associated with Altered Bile Acid Metabolism. J Pediatr Gastroenterol Nutr :|
|Shardell, Michelle; Semba, Richard D; Rosano, Caterina et al. (2016) Plasma Klotho and Cognitive Decline in Older Adults: Findings From the InCHIANTI Study. J Gerontol A Biol Sci Med Sci 71:677-82|
|Semba, Richard D (2016) The Rise and Fall of Protein Malnutrition in Global Health. Ann Nutr Metab 69:79-88|
Showing the most recent 10 out of 114 publications