Sarcopenia of aging is rapidly emerging as a major cause of many metabolic disorders and disabilities of increasing elderly population in our society. The current proposal investigates the effect of aging on muscle mitochondria which has substantial impact on both metabolic and mechanical function.
In Specific Aim 1 we will test a hypothesis that muscle mitochondrial ATP production decreases with age in three generations of women who inherit the same mitochondrial genome. We will also determine if stimulation of mitochondrial function by insulin and amino acids is reduced in older people. The phosphorylation of key proteins in signaling pathway for muscle protein synthesis will also be determined to detect any age-related defects. We will determine if oxidative damage increases with age and whether mitochondrial DNA copy numbers, mRNA levels of mitochondrial proteins, mitochondrial protein concentration, and activity of enzymes decrease in 12 families of three generations of women. The potential interaction of age and activity levels also will be investigated since alterations in activity levels have potential impact on mitochondrial function. Age-related changes in body composition may interact with age effect on mitochondria. Therefore, in Specific Aim 2 we will determine if obesity interacts with age on mitochondrial function. This is important because obesity is rapidly emerging as major public health problem especially in the aging population and may provide clues to the insulin resistance in aging. We have shown that amino acids have a stimulatory effect on muscle mitochondrial gene transcripts and functions but the impact of increasing protein intake on muscle mitochondrial functions remain to be defined. Therefore in Specific Aim 3 we will determine whether increasing the dietary protein content for 10 days enhances muscle mitochondrial functions and whether the response is similar in young and older people. The proposed studies will integrate information gathered from studies on mitochondrial DNA, gene transcript levels, protein concentrations and synthetic rates and metabolic changes to understand the underlying mechanisms of altered functions in aging muscle. Besides this primary objective, additional information on nuclear encoded proteins and gene transcript levels, and key proteins involved in signaling for muscle protein synthesis will also be obtained to better interpret the results on muscle mitochondria and to develop new hypotheses and approaches to understand the causes of sarcopenia of aging. These studies to understand the impact of age on muscle, may offer insights in to the agerelated changes in other predominant post-mitotic tissues such as brain and heart. Hopefully, the proposed studies and our continued commitment to further advance technology to test the emerging hypotheses from our ongoing research ensure substantial advance in our understanding of the biology of aging muscle.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Special Emphasis Panel (ZRG1-ASG (01))
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Dutta, Chhanda
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Mayo Clinic, Rochester
United States
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Robinson, Matthew M; Lowe, Val J; Nair, K Sreekumaran (2018) Increased Brain Glucose Uptake After 12 Weeks of Aerobic High-Intensity Interval Training in Young and Older Adults. J Clin Endocrinol Metab 103:221-227
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