Higher free-living activity energy expenditure is strongly associated with lower risks of coronary heart disease, cancer incidence, falls, and mortality among older adults. It is unknown, however, how activity energy expenditure can protect older adults from physical disability and premature mortality. The importance of mitochondrial function to the rate of progression of age-related diseases such as cancer, diabetes, and neurodegeneration has become increasingly apparent in recent years. Yet little is currently known about the role of mtDNA mutations in human bioenergetics. Our primary aim is to assess the association of mtDNA polymorphisms and heteroplasmy with active energy expenditure and resting metabolic rate in the elderly. We will carry out our primary aim in a test of healthy samples from the Health, Aging and Body Composition (Health ABC) Study cohort. Active energy expenditure and resting metabolic rate were measured in 1998-1999 in 302 high-functioning, community-dwelling older adults (aged 70-82 years). We will use the recently developed Affymetrix Mitochondrial Resequencing Array v2.0 (MitoChip) to sequence the entire mtDNA genome of 200 study participants from the highest and lowest tertiles of free-living activity energy expenditure (>770 kcal/d and <521 kcal/d, respectively). The results of this study may directly link mtDNA mutations with energy expenditure and metabolic rate in the elderly and provide a mechanism by which specific mtDNA mutational events contribute to bioenergenic decline and subsequent mortality. The results of our study may have profound biological and clinical significance. Identifying genetic variants that influence energy expenditure and metabolic rate could eventually lead to interventions that prolong the productive and healthy years of human life.
Our primary aim is to assess the association of mtDNA polymorphisms and heteroplasmy with active energy expenditure and resting metabolic rate in the elderly. We will carry out our primary aim in a test of healthy samples from the Health, Aging and Body Composition (Health ABC) Study cohort. We will use the recently developed Affymetrix Mitochondrial Resequencing Array v2.0 (MitoChip) to sequence the entire mtDNA genome of 200 study participants from the highest and lowest tertiles of free- living activity energy expenditure. The results of this study may directly link mtDNA mutations with energy expenditure and metabolic rate in the elderly and provide a mechanism by which specific mtDNA mutational events contribute to bioenergenic decline and subsequent mortality.
| Tranah, Gregory J; Maglione, Jeanne E; Yaffe, Kristine et al. (2018) Mitochondrial DNA m.13514G>A heteroplasmy is associated with depressive symptoms in the elderly. Int J Geriatr Psychiatry 33:1319-1326 |
| Tranah, Gregory J; Katzman, Shana M; Lauterjung, Kevin et al. (2018) Mitochondrial DNA m.3243A?>?G heteroplasmy affects multiple aging phenotypes and risk of mortality. Sci Rep 8:11887 |
| Buford, Thomas W; Manini, Todd M; Kairalla, John A et al. (2018) Mitochondrial DNA Sequence Variants Associated With Blood Pressure Among 2 Cohorts of Older Adults. J Am Heart Assoc 7:e010009 |
| Manini, Todd M; Buford, Thomas W; Kairalla, John A et al. (2018) Meta-analysis identifies mitochondrial DNA sequence variants associated with walking speed. Geroscience 40:497-511 |
| Tranah, Gregory J; Yaffe, Kristine; Katzman, Shana M et al. (2015) Mitochondrial DNA Heteroplasmy Associations With Neurosensory and Mobility Function in Elderly Adults. J Gerontol A Biol Sci Med Sci 70:1418-24 |
| Tranah, Gregory J; Santaniello, Adam; Caillier, Stacy J et al. (2015) Mitochondrial DNA sequence variation in multiple sclerosis. Neurology 85:325-30 |
| Katzman, Shana M; Strotmeyer, Elsa S; Nalls, Michael A et al. (2015) Mitochondrial DNA Sequence Variation Associated With Peripheral Nerve Function in the Elderly. J Gerontol A Biol Sci Med Sci 70:1400-8 |
| Tranah, Gregory J; Yokoyama, Jennifer S; Katzman, Shana M et al. (2014) Mitochondrial DNA sequence associations with dementia and amyloid-? in elderly African Americans. Neurobiol Aging 35:442.e1-8 |
| Tranah, Gregory J; Lam, Ernest T; Katzman, Shana M et al. (2012) Mitochondrial DNA sequence variation is associated with free-living activity energy expenditure in the elderly. Biochim Biophys Acta 1817:1691-700 |
| Tranah, Gregory J; Nalls, Michael A; Katzman, Shana M et al. (2012) Mitochondrial DNA sequence variation associated with dementia and cognitive function in the elderly. J Alzheimers Dis 32:357-72 |
Showing the most recent 10 out of 16 publications
