Abstract
Abstract Objectives Aging is associated with changes in body composition (eg. sarcopenia) but the overall effects of aging on systemic amino acid kinetics need further exploration. We previously reported metabolic differences in certain amino acids between young and older adults using comprehensive metabolic flux analysis. We expanded this novel single stable tracer pulse approach by the addition of several other isotopically-labeled amino acids to confirm and extend our findings in a new cohort of young and older adults. Methods We studied 18 healthy young (∼23 y, 9 females and 9 males) and 16 older adults (∼67 y, 8 females and 8 males) by administering a single dose of a mixture of stable amino acid tracers related to arginine-citrulline, glutamate, branched-chain amino acid (BCAA: leucine, isoleucine, valine), and protein-related metabolism. A baseline blood sample was collected before administration of the pulse tracer followed by 1.5 hours blood sampling protocol. We measured plasma enrichments by LC-MS/MS to calculate their whole body production (WBP) rates and metabolite interconversions. In addition, body composition by dual-energy X-ray absorptiometry was measured. Statistics were performed by unpaired student t-test. Results Older adults had a 13% higher Body Mass Index (P = 0.005) and 13% lower appendicular skeletal muscle index than the younger group (P = 0.04). WBP of glutamate was 26% lower (P < 0.05) in older adults whereas WBP of tau-methylhistidine was higher (31%, P = 0.045), in line with our previously reported data. In addition, older adults were characterized by lower WBP of all 3 BCAAs (P = 0.007), histidine (P = 0.001) and tryptophan (P = 0.003) by 17%, 16%, and 15%, respectively. However, higher whole-body production rates were observed for citrulline (24%, P = 0.036) and de novo arginine synthesis (21%, P = 0.027) in older adults. Conclusions Metabolic flux analysis reveals that the kinetics of a large set of amino acids differ between younger and older adults which indicates that amino acid metabolism is age-related. The clinical relevance of those changes needs further investigation. Funding Sources CTRAL Internal Funds.
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