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Human aging and somatic point mutations in mtDNA: A comparative study of generational differences (grandparents and grandchildren).

ABSTRACT: The accumulation of somatic mutations in mtDNA is correlated with aging. In this work, we sought to identify somatic mutations in the HVS-1 region (D-loop) of mtDNA that might be associated with aging. For this, we compared 31 grandmothers (mean age: 63 ± 2.3 years) and their 62 grandchildren (mean age: 15 ± 4.1 years), the offspring of their daughters. Direct DNA sequencing showed that mutations absent in the grandchildren were detected in a presumably homoplasmic state in three grandmothers and in a heteroplasmic state in an additional 13 grandmothers; no mutations were detected in the remaining 15 grandmothers. However, cloning followed by DNA sequencing in 12 grandmothers confirmed homoplasia in only one of the three mutations previously considered to be homoplasmic and did not confirm heteroplasmy in three out of nine grandmothers found to be heteroplasmic by direct sequencing. Thus, of 12 grandmothers in whom mtDNA was analyzed by cloning, eight were heteroplasmic for mutations not detected in their grandchildren. In this study, the use of genetically related subjects allowed us to demonstrate the occurrence of age-related (> 60 years old) mutations (homoplasia and heteroplasmy). It is possible that both of these situations (homoplasia and heteroplasmy) were a long-term consequence of mitochondrial oxidative phosphorylation that can lead to the accumulation of mtDNA mutations throughout life.

SUBMITTER: do Rosario Marinho AN

PROVIDER: S-EPMC3085369 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Human aging and somatic point mutations in mtDNA: A comparative study of generational differences (grandparents and grandchildren).

do Rosário Marinho Anderson Nonato AN de Moraes Milene Raiol MR Santos Sidney S Ribeiro-Dos-Santos Andrea A

Genetics and molecular biology 20110101 1

The accumulation of somatic mutations in mtDNA is correlated with aging. In this work, we sought to identify somatic mutations in the HVS-1 region (D-loop) of mtDNA that might be associated with aging. For this, we compared 31 grandmothers (mean age: 63 ± 2.3 years) and their 62 grandchildren (mean age: 15 ± 4.1 years), the offspring of their daughters. Direct DNA sequencing showed that mutations absent in the grandchildren were detected in a presumably homoplasmic state in three grandmothers an ...[more]

PMID: 21637539

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Project description:BackgroundCaring for grandchildren is regarded as one of the principle roles of middle- and old-aged adults, especially among rural Chinese grandparents. This study aims to examine the gender differences in depressive symptoms of rural Chinese grandparents caring for grandchildren, based on the gender differences in grandparental role engagement and the theories of role strain and role enhancement.MethodsA total of 4833 rural citizens with one or more grandchildren were selected from the China Health and Retirement Longitudinal Study (CHARLS) conducted in 2015. Grandchild care was measured by continuous variable (duration) and categorical variable (no care, low intensity, moderate intensity, high intensity). Depressive symptoms were assessed by the Center for Epidemiologic Studies Depression Scale (CES-D). We used coarsened exact matching (CEM) to balance the covariates of caregivers and non-caregivers. Following CEM, 1975 non-caregivers and 2212 caregivers were identified (N = 4187). Multilevel linear regression was employed to examine the gender differences in depressive symptoms. We also tested for the moderating role of gender on the association between grandchild care and depressive symptoms.ResultsGrandmothers were more likely to provide grandchild care (54.42% vs 51.43%) at high intensity (61.46% vs 51.01%), with longer duration (39.24 h vs 33.15 h) than that given by grandfathers. Grandmothers suffered more from depressive symptoms than grandfathers, and such gap increased when grandparents were involved in high-intensity care. Grandmothers providing grandchild care, particularly at moderate intensity, were associated with fewer depressive symptoms (Coef. = - 0.087, 95%CI: - 0.163, - 0.010; Coef. = - 0.291, 95%CI: - 0.435, - 0.147), compared with non-caregivers. Grandmothers giving moderate intensity of grandchild care were also associated with fewer depressive symptoms (Coef. = - 0.171, 95% CI: - 0.313, - 0.029), compared with those with low-intensity care. However, such associations were not significant among grandfathers.ConclusionsOur findings highlight the gender differences in depressive symptoms of rural Chinese grandparents caring for grandchildren. Grandparents should be encouraged to engage in grandchild care, but at moderate intensity. The health status of middle- and old-aged adults, particularly females, should be monitored closely. Humanistic care, preventive care and curative treatment strategies focusing on such populations should be developed and refined.

Dataset Information

Human aging and somatic point mutations in mtDNA: A comparative study of generational differences (grandparents and grandchildren).

Publications

Human aging and somatic point mutations in mtDNA: A comparative study of generational differences (grandparents and grandchildren).

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