We'll Pay $101 Million If You Prove You Can Reverse Aging

Comment.

The exceptions to wear and tear, free radical oxidative stress theory of aging were explained by the membrane pacemaker theory of aging. And the exceptions to membrane pacemaker can be explained by presence of molecules such as plasmalogens that are not normally taken into account when calculating Peroxidation index. It is conceivable lowering membrane damage sufficiently would allow repair mechanisms to outclass rate of damage accumulation

Interesting longevity finding regarding astaxanthin.

An Astaxanthin compound has been found to switch on the FOX03 'Longevity Gene' in a study using mice. Researchers measured a nearly 90% increase in the activation of the gene in the animals' heart tissue. Life sciences company Cardax, Inc. looks forward to further confirmation in human clinical trials of Astanxanthin's potential role as an anti-aging therapy. -link

Interesting finding.   The fact that astaxanthin increases lifespan in some species, and also appears to protect cell membranes, make it very promising.

Increasing membrane unsaturation with aging and longevity

It has now been documented that there is an age-associated increase in membrane PI and lipoxidation-derived molecular damage (see Table ​Table1).1). In general, PI increases during aging in an organ-dependent way.  -http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865700/

As seen on the above quote it seems that membranes peroxidation index tends to become less favorable with the passage of time, at least in some organisms.   Given that differences in membrane peroxidation index have been associated with differences in lifespan between species and within species this suggest it may be causal.

In the following we see further evidence:

The results showed significantly lower PI and lipoxidation-derived protein damage in brain and spleen from exceptionally old animals when compared to old specimens, and in a range analogous to adult animals. Therefore, low susceptibility to lipid peroxidation and maintenance of adult-like molecular lipoxidative damage could be key factors for longevity achievement.-http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865700/

 The animals that exhibited most vigorous long term survival seemed to have lower PI similar to younger adults.   While the authors suggest it may be a key to longevity, I would say it may also be a key to indefinite longevity.   It may or may not be the case that if PI is lowered enough the existing biological maintenance and repair mechanisms may be enough to grant negligible senescence.   I would predict that organisms showing negligible senescence would show such peroxidation resistance, that is they would have a lower PI and it may even be significantly lower(depending on threshold or break even point for indefinite homeostatic balance/maintenance), and a quick wikipedia search shows just that in at least one organism

 Abstract:
Summary: 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 with 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 year) to four other sympatric bivalve molluscs greatly differing in longevity (28, 37, 92, and 106 year). 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 whether 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.

^ Munro, D., and Blier P.U. (2012). The extreme longevity of Arctica islandica is associated with increased peroxidation resistance in mitochondrial membranes. Ageing Cell 11(5): 845-55. doi: 10.1111/j.1474-9726.2012.00847.x. Epub 2012 Jul 25.-wikipedia
 

Few snippets on aging

 Compared to other elderly, membranes from centenarians (> 100 yrs) showed:
1) decreased lipid peroxide levels and reduced susceptibility to peroxidation
2) increased unsaturated/saturated fatty acid ratio
3) higher levels of EPA and DHA, reduced LA and AA
4) higher fluidity 
Membranes from centenarians show some distinct features in comparison with elderly subjects that might act in a protective way against injuries
 -http://www.waiworld.com/waitalk/phpBB3/viewtopic.php?f=20&t=3385

The above is from a thread where the topic of membrane composition, peroxidation and lifespan is covered

I was reading the book Neurons and the DHA Principle, and it seems that neuron's have substantial polyunsaturated fat content in membranes but can overcome this by antioxidant defenses.   Given these are the longest lived cells in the body and can function for over 120 years(oldest human is said to've been free from dementia), it suggests to me that if some lipid soluble antioxidant was found that didn't turn pro-oxidant nor significantly interfered with ROS signalling it could be an overall positive.

The accumulation of lipofuscin-like material may be the result of an imbalance between formation and disposal mechanisms: Such accumulation can be induced in rats by administering a protease inhibitor (leupeptin); after a period of three months, the levels of the lipofuscin-like material return to normal, indicating the action of a significant disposal mechanism.^[3] However, this result is controversial, as it is questionable if the leupeptin-induced material is true lipofuscin.^[4][5] There exists evidence that "true lipofuscin" is not degradable in vitro;^[6][7][8] whether this holds in vivoover longer time periods is not clear.-link

Assuming the cells can't actually digest it, all that would be necessary is some mechanism to export the waste and discard it elsewhere.   Whether such a mechanism exists is a good question, but I think it is likely. 

We report that long-term overexpression of
Parkin can eliminate mitochondria with deleterious COXI mutations
in heteroplasmic cybrid cells, thereby enriching cells for wild-type
mtDNA and restoring cytochrome coxidase activity.-link

Emerging data indicate that selective mitochondrial degradation through autophagy (mitophagy) plays a critical role in mitochondrial quality control. Inhibition of mammalian target of rapamycin (mTOR) kinase activity can activate mitophagy. To test the hypothesis that enhancing mitophagy would drive selection against dysfunctional mitochondria harboring higher levels of mutations, thereby decreasing mutation levels over time-link

The mitochondria has its own dna, it codes for vital functions not redundantly covered in the nucleus.  It is subject to direct exposure to damaging reactive species, so it can become dysfunctional much more easily than the dna in the nucleus.   An obvious question was how can such an organelle subject to far more mutational damage not lead to extinction of most any species.   A method of quality control has been found in female reproductive systems, iirc at the level of discarding cells, again iirc.   But it opened the question as to whether an intracellular method of quality control might also exist(after all neurons last for over a century of high metabolic activity and they don't divide).  As the above two links show it seems very likely there is a method of quality control that can preserve mitochondrial quality.