For almost half a century, it was thought that mitochondrial DNA (mtDNA) and oxidative stress were the major contributors to aging. This theory was postulated by Harman in the 70’s, where two independent groups tried the hypothesis on mtDNA Mutator mice, where they accumulated the mutations and showed progressing aging signs, including grey hair, thin skin, osteoporosis and anemia. It was therefore concluded that mtDNA mutagenesis drives aging.
Following the experiment, several groups conducted rigorous studies but could not find elevated oxidative stress in the Mutator mouse tissues. This led many to question the Mitochondrial aging theory and ask for an alternative explanation for mitochondrial progeria. A recent study published in Nature Metabolism has thus found that disturbances in the function of mitochondrial DNA can speed up aging in ways different than previously thought.
The current study explains that mDNA Mutator mice have compromised nuclear DNA maintenance stem cells. Meaning, the DNA defects in their stem and progenitor cells such as increased DNA-breaks and activation of DNA damage response pathways that occurs during the nuclear genome replication, are the real causative agents in the aging process.
SEE ALSO: Decoded: The End of Aging
The effects of aging manifested in Mutator mouse’s phenotype were found strikingly similar to other mouse progeria models and human progeric syndromes with nuclear genome instability as the most prominent defect. The difference could be ascertained due to the fact that Progeria is not a clinical feature of mitochondrial disease patients, even the ones with high amounts of mt DNA mutations.
So how can a primary mitochondrial DNA maintenance defect affect maintenance of nuclear genome? The authors showed the increased mtDNA replications against disappearing DNA building blocks, dNTPs into mitochondria which meant lesser dNTPs were going in for nuclear genome maintenance and ultimately slowing down replication and DNA damage.
Original Source: https://in.mashable.com/science/7503/mitochondrial-aging-theory-is-a-myth-aging-lies-in-the-nucleus