Mitochondria Accumulate Harmful Mutations As We Age

Many believe mitochondrial mutations are a driving force in the aging process, and new research has confirmed mitochondria indeed accumulate mutations as we get older

While some people support the mitochondrial theory of aging, many scientists now agree there are many hallmarks of aging that likely work together to drive the process. It’s been known for a while mitochondria play some kind of role, but the evidence has been lacking. Now, mutations have been exposed in mitochondria within induced pluripotent stem cells – created from adult skin cells. This means that induced stem cells need more robust screening, and confirms mitochondrial mutations are a strong anti-aging target. 

“Pathogenic mutations in our mitochondrial DNA have long been thought to be a driving force in aging and age-onset diseases, though clear evidence was missing. Now with that evidence at hand, we know that we must screen stem cells for mutations or collect them at younger age to ensure their mitochondrial genes are healthy. This foundational knowledge of how cells are damaged in the natural process of aging may help to illuminate the role of mutated mitochondria in degenerative disease”

Your mitochondria are vulnerable

Mutations in the mitochondrial genome have been linked to many diseases

Although the vast majority of your genes are housed in a cell’s nucleus a few specific genes remain in the mitochondrial genome. It’s tricky to get machinery and material into the mitochondria, so it’s easier for them to produce some of their own proteins. While the majority of genes were gradually transferred to the nucleus as evolution progressed, unfortunately those genes that remain are inherently vulnerable.

DNA in the nucleus does undergo some mutation, but it’s largely protected from damage. Mitochondria however are exposed to reactive molecules and free radicals all the time as they pump out energy. This means mitochondrial genes are far more likely to mutate, and indeed do. Because of this your cells have mechanisms to recycle and get rid of faulty mitochondria, but there are certain mutations that make mutated mitochondria able to escape destruction. 

Hidden mutations pass to stem cells

Stem cells derived from older patients contained more mitochondrial mutations. Credit: Mitalipov et al./Cell Stem Cell 2016

To work out whether harmful mitochondrial mutations could be present in stem cells made from adult cells, researchers took samples of blood and skin from patients ranging from 24 to 72. When they tested these for mutations they didn’t find any notable increases, but when they created induced pluripotent stem cells(iPSCs) from those samples they found higher levels of mitochondria mutations in patients above 60 especially. 80% of the 130 cell lines created displayed these mutations, which is a worrying sign. 

The need for screening

You have many mitochondria per cell, and if the majority are healthy the cell will usually function normally. More work needs to be done on exactly which mutations are harmful, but the research proves we need greater screening of iPSC cell lines to ensure they’re safe to use. Sequencing could be done relatively quickly to pick healthy cells, or known healthy mitochondria from a younger patient could be transferred to these stem cells. 

More proof mitochondria may drive aging

The study didn’t expand on what was happening across the body, but it suggests these mutations build as we get older. The SENS foundation is already working on a solution to this issue by moving mitochondrial genes into the nucleus where they’ll be safer. As more research is conducted, we’ll hopefully better understand exactly what’s going on in our cellular batteries as we age, and what we can do about it. 

Read more at MedicalXpress