Abstract
Energy expenditure decreases with age, but in the oldest-old, energy demand for maintenance of body functions increases with declining health. Uncoupling proteins have profound impact on mitochondrial metabolic processes; therefore, we focused attention on mitochondrial uncoupling protein genes. Alongside resting metabolic rate (RMR), two SNPs in the promoter region of UCP2 were associated with healthy aging. These SNPs mark potential binding sites for several transcription factors; thus, they may affect expression of the gene. A third SNP in the 3′-UTR of UCP3 interacted with RMR. This UCP3 SNP is known to impact UCP3 expression in tissue culture cells, and it has been associated with body weight and mitochondrial energy metabolism. The significant main effects of the UCP2 SNPs and the interaction effect of the UCP3 SNP were also observed after controlling for fat-free mass (FFM) and physical-activity related energy consumption. The association of UCP2/3 with healthy aging was not found in males. Thus, our study provides evidence that the genetic risk factors for healthy aging differ in males and females, as expected from the differences in the phenotypes associated with healthy aging between the two sexes. It also has implications for how mitochondrial function changes during aging.
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Acknowledgments
We thank the people of Louisiana for participation in our studies. We also thank Katie Kwong, Natalie Harold, and Tiffany Kaul in graduate programs for their help with data management. This study was supported by grants from the National Institute on Aging of the National Institutes of Health (P01AG022064 to S.M.J.), the National Institute of General Medical Sciences of the National Institutes of Health (P20GM103629) to S.M.J. and S.K., the Louisiana Board of Regents through the Millennium Trust Health Excellence Fund [HEF(2001–06)-02] to S.M.J, Support from Pennington NORC P30DK072476 (E.R.), and by the Louisiana Board of Regents RC/EEP Fund through the Tulane-LSU CTRC at LSU Interim University Hospital.
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Kim, S., Myers, L., Ravussin, E. et al. Single nucleotide polymorphisms linked to mitochondrial uncoupling protein genes UCP2 and UCP3 affect mitochondrial metabolism and healthy aging in female nonagenarians. Biogerontology 17, 725–736 (2016). https://doi.org/10.1007/s10522-016-9643-y
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DOI: https://doi.org/10.1007/s10522-016-9643-y