Maternally transmitted mitochondrial DNA mutations can reduce lifespan
Jaime M Ross1, Giuseppe Coppotelli1, Barry J Hoffer2
1Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 171 77 Stockholm, Sweden.
Abstract:
We recently showed that germline transmission of mitochondrial DNA mutations via the oocyte cause aggravation of aging phenotypes in prematurely aging mtDNA mutator (PolgA(mut/mut)) mice. We discovered that 32% of these mice also exhibit stochastic disturbances of brain development, when maternal mtDNA mutations were combined with homozygosity for the PolgA mutation, leading to de novo somatic mtDNA mutations. Surprisingly, we also found that maternally transmitted mtDNA mutations can cause mild premature aging phenotypes also in mice with a wild-type nuclear DNA background. We now report that in addition to the early onset of aging phenotypes, these mice, burdened only by low levels of mtDNA mutations transmitted via the germline, also exhibit reduced longevity. Our data thus demonstrate that low levels of maternally inherited mtDNA mutations when present during development can affect both overall health and lifespan negatively.
Insights
Maternally inherited mitochondrial DNA (mtDNA) mutations can negatively impact health and longevity, even at low levels. These mutations, transmitted via the egg, contribute to premature aging and reduced lifespan in mice.
Area of Science:
- Mitochondrial genetics
- Developmental biology
- Aging research
Background:
- Germline transmission of mitochondrial DNA (mtDNA) mutations via oocytes can worsen aging phenotypes.
- Maternal mtDNA mutations combined with nuclear mutations (PolgA(mut/mut)) lead to de novo somatic mtDNA mutations and brain development issues.
- Maternally transmitted mtDNA mutations can induce mild premature aging in mice with wild-type nuclear DNA.
Purpose of the Study:
- To investigate the impact of low levels of maternally inherited mtDNA mutations on aging phenotypes and longevity.
- To determine if low-level germline mtDNA mutations affect healthspan and lifespan in a wild-type nuclear background.
Main Methods:
- Utilizing prematurely aging mtDNA mutator (PolgA(mut/mut)) mice and wild-type mice.
- Analyzing the effects of maternally transmitted mtDNA mutations on aging phenotypes and longevity.
- Assessing developmental disturbances and de novo somatic mtDNA mutations.
Main Results:
- Mice with maternally inherited mtDNA mutations, even at low levels and in a wild-type nuclear background, exhibit early-onset aging phenotypes.
- These mice also show significantly reduced longevity compared to controls.
- The presence of mtDNA mutations during development negatively affects overall health and lifespan.
Conclusions:
- Low levels of maternally inherited mtDNA mutations can negatively impact both healthspan and lifespan.
- Germline mtDNA mutations are a significant factor in aging and longevity, independent of nuclear genetic background.
- Understanding the role of mtDNA transmission is crucial for aging and developmental research.
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