Mitochondrial Membrane Resistance to Explain Clam Longevity
You might recall the species of clam that can live for at least four centuries. Similarly, you might also recall the membrane pacemaker hypothesis that explains differences in longevity between species in terms of the resistance of cell membranes - and especially mitochondrial membranes - to damage. Here, the two topics are linked: "The deleterious reactive carbonyls released upon oxidation of polyunsaturated fatty acids in biological membranes are believed to foster cellular aging. Comparative studies in mammals and birds have shown that the susceptibility to peroxidation of membrane lipids (peroxidation index, PI) is negatively correlated to longevity. Long-living marine molluscs are increasingly studied as longevity models, and the presence of different types of lipids in the membranes of these organisms raises questions on the existence of a PI-longevity relationship. We address this question by comparing the longest-living metazoan species, the mud clam Arctica islandica (maximum reported longevity = 507 y) to four other sympatric bivalve molluscs greatly differing in longevity (28, 37, 92, and 106 y). We contrasted the acyl and alkenyl chain composition of phospholipids from the mitochondrial membranes of these species. The analysis was reproduced in parallel for a mix of other cell membranes to investigate if a different PI-longevity relationship would be found. The mitochondrial membrane PI was found to have an exponential decrease with increasing longevity among species and is significantly lower for A. islandica. The PI of other cell membranes showed a linear decrease with increasing longevity among species and was also significantly lower for A. islandica. These results clearly demonstrate that the PI also decreases with increasing longevity in marine bivalves and that it decreases faster in the mitochondrial membrane than in other membranes in general. Furthermore, the particularly low PI values for A. islandica can partly explain this species' extreme longevity." This emphasizes the importance of mitochondrial damage in aging and longevity, and thus the importance of research into mitochondrial repair biotechnologies for humans.
From the online literature, it seems reasonable to conjecture that mitochondrial free radicals could drive the speed of development and differentiation, and may not just be unavoidable metabolic byproducts.
Is it possible that some (or most) free radicals are "intentionally" generated as part of the developmental program which continues past the point of maturation, when the pleiotropy becomes obvious as aging?
If so, the "damage" would not be reversed by only repairing mitochondria.
@Lou Pagnucco: Per my understanding of the mitochondrial free radical theory of aging, the problem is that a comparatively small flux of free radicals damages mitochondrial membranes in a way that causes bad mitochondria to propagate and turn whole cells into generators of a large flux of free radicals.
The signalling levels of free radicals (e.g. that stimulate muscle maintenance) are, I believe, small in comparison to what is generated by cells gone bad.
But the picture is complicated, and there's room to argue that all sorts of other mechanisms are in play and confounding the picture.
Still, at this point it seems that the answer to "is repairing mitochondria going to do good" will be most efficiently answered by going ahead and repairing mitochondria - that goal looks just as close as the amount of research needed to answer that question without actually repairing mitochondria.
My fear is that the "damage" theories are damaging research.
For instance, why do differentiated cells down-regulate their anti-oxidant production faster that stem cells? Why would they be subject to more "noise" than stem cells? Here are a few papers that make me question the "wear and tear" theories:
"Is caspase-dependent apoptosis only cell differentiation taken to the extreme?
http://www.fasebj.org/content/21/1/8.full.pdf
"Regulation of cell differentiation by the DNA damage response"
http://www.teitell-lab.com/PDF_Files/2011_4_Sherman.pdf
"Genomic Stability in Stem Cells"
http://www.gwumc.edu/smhs/anatomy/sites/default/files/iriz4.pdf