title: Single nucleotide polymorphisms linked to mitochondrial uncoupling protein genes UCP2 and UCP3 affect mitochondrial metabolism and healthy aging in female nonagenarians.
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.
authors.affiliation: Tulane Center for Aging and Department of Medicine, Tulane University Health Sciences Center, 1430 Tulane Ave, SL-12, New Orleans, LA, 70112, USA. skim5@tulane.edu.
authors.forename: Sangkyu
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Biostatistics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University Health Sciences Center, New Orleans, LA, USA.
authors.forename: Leann
authors.initials: L
authors.lastname: Myers
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, LA, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Ravussin
authors.affiliation: Department of Psychology, Louisiana State University, Baton Rouge, LA, USA.
authors.forename: Katie E
authors.initials: KE
authors.lastname: Cherry
authors.affiliation: Tulane Center for Aging and Department of Medicine, Tulane University Health Sciences Center, 1430 Tulane Ave, SL-12, New Orleans, LA, 70112, USA.
authors.forename: S Michal
authors.initials: SM
authors.lastname: Jazwinski
mesh_terms: D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D004734:Energy Metabolism / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006801:Humans; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012727:Sex Characteristics; D000071246:Uncoupling Protein 2 / Q000235:genetics*; D000071247:Uncoupling Protein 3 / Q000235:genetics*
chemical_list: C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
keywords: Energy metabolism; Frailty; Healthy aging; Mitochondrial uncoupling; Single nucleotide polymorphism