|MANINI, TODD - University Of Florida|
|BUFORD, THOMAS - University Of Alabama|
|KAIRALLA, JOHN - University Of Florida|
|MCDERMOTT, MARY - Northwestern University|
|VAZFRAGOSO, CARLOS - Yale University|
|FIELDING, ROGER - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|HSU, FANG-CHI - Wake Forest University|
|JOHANNSEN, NEIL - Pennington Biomedical Research Center|
|KRITCHEVSKY, STEPHEN - Wake Forest University|
|HARRIS, TAMARA - National Institute On Aging (NIA, NIH)|
|NEWMAN, ANNE - University Of Pittsburgh|
|CUMMINGS, STEVE - California Pacific Medical Center|
|KING, ABBY - Stanford University|
|PAHOR, MARCO - University Of Florida|
|SANTANASTO, ADAM - University Of Pittsburgh|
|TRANAH, GREGORY - California Pacific Medical Center|
Submitted to: GeroScience
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/6/2018
Publication Date: 10/18/2018
Citation: Manini, T.M., Buford, T.W., Kairalla, J.A., McDermott, M.M., Vazfragoso, C.A., Fielding, R.A., Hsu, F., Johannsen, N., Kritchevsky, S., Harris, T.B., Newman, A.B., Cummings, S.R., King, A.C., Pahor, M., Santanasto, A.J., Tranah, G.C. 2018. Meta-analysis identifies mitochondrial DNA sequence variants associated with walking speed. GeroScience. https://doi.org/10.1007/s11357-018-0043-x.
Interpretive Summary: Age-related declines in walking speed are associated with a variety of poor health outcomes, including disability, comorbidity, and death. While genetic factors may be contributors to declines in walking speed, few genetic variations have been identified for this trait. We examined the role of mitochondrial DNA variations on walking speed by sequencing the entire mitochondrial genome. Data were analyzed from 1,758 Lifestyle Interventions and Independence for Elders (LIFE) Study participants and validated in 730 Health, Aging, and Body Composition (HABC) Study participants with baseline walking speed information. Participants were at least 69 years old, of diverse racial backgrounds, and had a wide range of average walking speeds. Analysis across both studies and racial groups showed that there were specific mitochondrial DNA variants significantly associated with walking speed. These results could lead to identifying those at risk of developing mobility impairments.
Technical Abstract: Declines in walking speed are associated with a variety of poor health outcomes including disability, comorbidity, and mortality. While genetic factors are putative contributors to variability in walking, few genetic loci have been identified for this trait. We examined the role of mitochondrial genomic variation on walking speed by sequencing the entire mitochondrial DNA (mtDNA). Data were meta-analyzed from 1758 Lifestyle Interventions and Independence for Elders (LIFE) Study and replication data from 730 Health, Aging, and Body Composition (HABC) Study participants with baseline walking speed information. Participants were 69+ years old of diverse racial backgrounds (African, European, and other race/ethnic groups) and had a wide range of mean walking speeds [4-6 m (0.78-1.09 m/s) and 400 m (0.83-1.24 m/s)]. Meta-analysis across studies and racial groups showed that m.12705C>T, ND5 variant was significantly associated (p<0.0001) with walking speed at both short and long distances. Replication and meta-analysis also identified statistically significant walking speed associations (p<0.0001) between the m.5460.G>A, ND2 and m.309C>CT, HV2 variants at short and long distances, respectively. All results remained statistically significant after multiple comparisons adjustment for 499 mtDNA variants. The m.12705C>T variant can be traced to the beginnings of human global migration and that cells carrying this variant display altered tRNA expression. Significant pooled effects related to stopping during the long-distance walk test were observed across OXPHOS complexes I (p=0.0017) and III (p=0.0048). These results suggest that mtDNA-encoded variants are associated with differences in walking speed among older adults, potentially identifying those at risk of developing mobility impairments.