hourglass aging

New research challenges aging consensus by reversing mitochondrial anomalies in 97-year-old cells

A team led by Professor Jun-Ichi Hayashi from the University of Tsukuba in Japan, known as the white lion to his students given his white hair and powerful voice, challenges the current consensus surrounding the mitochondrial theory of aging, proposing epigenetic regulation, and not genetic mutation, may be responsible for the age-related effects seen in mitochondria. When Hayashi and colleagues tested their theory, they reversed the age defects in cell lines collected from 97-year-old Japanese participants. They then singled out two genes involved in glycine production which they believed are responsible for the mitochondria reversal. The findings thus suggest that a glycine supplementation could help curb aging or age-related diseases.

hourglass aging

Image: Huff Post

Mitochondria are popularly known as the “cell’s powerhouse”, since they’re responsible for producing energy through cellular respiration. One of the unique features of mitochondria is that they contain their own DNA – mitochondrial DNA (mtDNA). All the other DNA of a cell is found in the nucleus (nDNA). Most scientists claim that the mitochondria through mutations sustained in its DNA is involved in aging, since the mutations cause abnormal functions.

The mitochondrial theory of aging (MTA) was first proposed in 1972 by Denham Harman, the “father” of the free radical theory of aging (FRTA). Basically, as we age these mutations add up and the mitochondria is less efficient at producing energy, reducing lifespan and triggering aging-related characteristics such as weight and hair loss, curvature of the spine and osteoporosis. The brain is perhaps the most important organ affected by aging, since it consumes more energy than any other organ of the body. An energy deficit in the brain and central nervous system affects the activities of all organs throughout the body as well as mental acuity and mood.

Professor Hayashi. Credit: Image courtesy of University of Tsukuba

Professor Hayashi. Credit: Image courtesy of University of Tsukuba

Hayashi’s team, however, claims that the MTA has one severe flaw: it’s not DNA mutation, but epigenetic regulations that cause the mitochondrial defects. They collected  human fibroblast cell lines derived from young people (ranging in age from a fetus to a 12 year old) and elderly people (ranging in age from 80-97 years old). Then mitochondrial respiration and the amount of DNA damage in the mitochondria of the two groups was studied. Hayashi  expected to see reduced mitochondrial respiration and more DNA damage in the older cells, but while the elderly group indeed showed reduced respiration, there DNA differences between the two groups was minute. This is when they got the idea that epigenetics – environmental changes that alter the structure of DNA, without affecting its sequence – may have a part to play.

If they were right, then changing cells by genetically reprogramming them into an embryonic stem cell-like state would cancel any epigenetic effects. So, they put it to the test and the human fibroblast cell lines from both young and old participants were then converted into a stem-like state, then turned back into fibroblasts and their mitochondrial respiratory function examined. In an amazing twist of events, all of the resulting mitochondria had respiration rates comparable to those of the fetal fibroblast cell line, irrespective of whether they were derived from young or elderly people. This provides significant evidence to back their claim that mitochondria anomalies, and subsequently human cell aging, are governed by epigenetics.

They then identified two genes that might be controlled epigenetically and cause the age-related defects. The genes, CGAT and SHMT2, regulate glycine production in mitochondria. Glycine is the smallest of the amino acids. It is ambivalent, meaning that it can be inside or outside of the protein molecule.

Moreover, by changing the expression of these two genes, the team showed they could induce defects or restore mitochondrial function in the fibroblast cell lines. For instance, adding glycine for 10 days to the culture medium of the 97 year old fibroblast cell line restored its respiratory function, as reported in Scientific Reports. But could it work for other types of cells? If so, then human aging could be slowed down or even hampered using something like glycen supplements. Of course, this is but a part of the aging puzzle. There are also other things we need to worry about like telomerase length, stem cell death, cancer, transcription error to name but a few.

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