Since we started discussing it on the Genetics of Obesity thread, I've gotten interested in epigenetics, the regulation of gene expression by environmental factors.
By far the best introduction to the mechanism and significance of epigenetics that I've come across is this video of a three leading researchers in the field discussing it at the World Science Festival. Its long (1:20min), but I highly recommend it for anyone interested in learning about this fascinating and important subject. It has a good 10min explanation (with graphics) starting at 10:30sec of histones, methylation, acetylation, etc. Here is the key graphic depicting how the double helix of DNA can be wrapped up (preventing transcription) or unwrapped (allowing transcription) from their histones "spools" by methyl groups (Me) or acetyl groups (Ac), respectively (click to enlarge):
This wrapping and unwrapping of DNA to control its transcription seems to be a (the?) key epigenetic regulatory mechanism by which environmental factors can influence gene expression, and therefore health.
With that background, I came across this interesting recent study  on the importance of epigenetics for mitochondrial dysfunction. Recall the mitochondrial free radical theory of aging holds that since mitochondria are the "powerhouse" of the cell, they generate the most free radicals, and therefore are most likely to cause mutations in both their own (i.e. mitochondrial) DNA as well as nuclear DNA, which in turn leads to the mitochondria not working as well to produce energy, and to other free radical-induced cellular dysfunction.
But this new study , seems to call this standard model of free radical-induced cellular aging into question, and instead suggest that mitochondrial dysfunction may be a result of epigenetic "programming".
The authors first compared the mitochondria of fibroblast cells (collagen-producing cells responsible for connective tissue synthesis/maintenance) in cell lines extracted from young children and elderly people. They found that old fibroblasts were indeed impaired in their rate of respiration compared with the young cells, as expected. But surprisingly, the old fibroblasts didn't exhibit more mitochondrial mutations of various types than the young fibroblasts. Nor did the old cells seem to be producing more free radicals than the young cells.
So the authors figured "hey, maybe these old mitochondria aren't really damaged, but are just not working well because of their epigenetic programming." So they reset the old fibroblasts by genetically reprogramming them to an embryonic stem cell-like state, figuring this would remove any epigenetic changes associated with the mitochondrial DNA.
Sure enough, they found that when the cells were converted to stem cells and then back to fibroblasts, their respiration rate returned to the same level as the young fibroblasts. Since their 'old' DNA was preserved by this procedure, this would seem to show that neither mitochondrial nor nuclear DNA mutations were the cause of their original dysfunction.
The researchers then looked for genes that might be controlled epigenetically resulting in these age-associated mitochondrial defects. Two genes that regulate glycine production in mitochondria, CGAT and SHMT2, were found. The researchers showed that by changing the regulation of these genes, they could induce defects in young fibroblasts, or restore mitochondrial function in old fibroblast cells, supporting their hypothesis that the old mitochondria weren't working because of epigenetic programming, rather than because of free radical-induced damage.
Interestingly, in the conclusion section the authors' speculate about the possible benefits of glycine supplementation in the elderly to improve mitochondrial function:
Because continuous glycine treatment restored respiration defects in elderly human fibroblasts (Supplementary Fig. 6), glycine supplementation may be effective in preventing age-associated respiration defects and thus benefiting the health of elderly human subjects.
Michael, since you are the resident expert on the mitochondrial free radical theory of aging, perhaps you could comment on the results of this paper and their implications?
 Sci Rep. 2015 May 22;5:10434. doi: 10.1038/srep10434.
Epigenetic regulation of the nuclear-coded GCAT and SHMT2 genes confers human
age-associated mitochondrial respiration defects.
Hashizume O(1), Ohnishi S(1), Mito T(1), Shimizu A(1), Iashikawa K(1), Nakada
K(2), Soda M(3), Mano H(3), Togayachi S(4), Miyoshi H(5), Okita K(6), Hayashi
Full Text: http://www.nature.co...icles/srep10434
Age-associated accumulation of somatic mutations in mitochondrial DNA (mtDNA) has
been proposed to be responsible for the age-associated mitochondrial respiration
defects found in elderly human subjects. We carried out reprogramming of human
fibroblast lines derived from elderly subjects by generating their induced
pluripotent stem cells (iPSCs), and examined another possibility, namely that
these aging phenotypes are controlled not by mutations but by epigenetic
regulation. Here, we show that reprogramming of elderly fibroblasts restores
age-associated mitochondrial respiration defects, indicating that these aging
phenotypes are reversible and are similar to differentiation phenotypes in that
both are controlled by epigenetic regulation, not by mutations in either the
nuclear or the mitochondrial genome. Microarray screening revealed that
epigenetic downregulation of the nuclear-coded GCAT gene, which is involved in
glycine production in mitochondria, is partly responsible for these aging
phenotypes. Treatment of elderly fibroblasts with glycine effectively prevented
the expression of these aging phenotypes.
PMID: 26000717 [PubMed - in process]
Edited by Dean Pomerleau, 12 September 2015 - 02:22 PM.
There will never be peace in the world while there are animals in our bellies.