Comment on aging regards Gene expression vs more radical changes as pertains lifespan increases.

At least at the cellular level, it seems altering gene expression makes old cells indistinguishable from young cells in the lab under a microscope.   If you go by what Bill Andrews and Michael Fossel comment, iirc.

Some of them(Fossel, iirc) seem to believe that if gene expression is changed, the body will clear the garbage out.    The inability to process garbage locally shouldn't be too concerning, as systems like the brain have the glymphatic system that routinely exports molecular garbage out(when it malfunctions you get neurodegeneration diseases, when not you get superagers with 20 year old brain function.).   It is likely, imho, in young animals the lymphatic system plays a similar role and exports molecular garbage out of tissues.   But with aging it is compromised, and along with increased garbage production, garbage starts  to accumulate.

In human society houses don't process all of their garbage, they merely export it out for disposal or recycling, wouldn't surprise if nature does similar.   Look at the brain for example, an extremely high metabolism organ, neurons have similar metabolic costs between species, yet we live 3 times as long as bonobos who share 98% of our genes.  Our common ancestor likely had similar short lifespan, but to increase the lifespan, even tripling it, even of organs like the brain, it was mostly gene expression changes that allowed it, not novel radical mechanisms.-link to source

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.

Comment on fightaging telomerase article

"Contrast that with the SENS hypothesis that aging is molecular and cellular damage that the body cannot repair at any reasonable cost."

If that were the case, we should see SENS like approaches being implemented by nature in negligible Senescence species. If all they've is mostly the same genes and differing expression patterns, then existing mechanisms are sufficient if ramped up. We have over 98% genetic similarity with our closest relative yet over twice the lifespan.

What approach doubled species lifespan?

If we were bonobos with 40year lifespans and we asked SENS proponents. They'd say most of the [easy] longevity changes were already implemented by nature in achieving this lifespan and they'd propose the SENS solutions as a way to lengthen lifespan.

If like me you believed existing mechanisms are mostly sufficient for vast lifespan increase, then you'd suggest mostly gene expression changes with high conservation of the genome. What did nature do? AFAIK, it simply mostly tweaked gene expression and presto triple lifespan.

If you ask me, it is likely that similar tweaks could very likely carry us all the way up to negligible senescence.

 Let's see what we find from the genetic sequences of negligible senescence organisms.

"Indeed; it's not like there aren't plenty of species whose telomeres don't shorten with age, in fact there's a species of bird whose telomeres get -longer- with increasing age, and it ages quite normally."

I've not looked into it deeply, but according to Dr. Bill Andrews, it is only a few species who have significant aging contribution from short telomeres.

"The same thing should happen if you were to repair all the cellular and molecular damage of aging that suppresses stem cell activity."

And it also as mentioned seems to slightly begin to occur with lifestyle changes that increase telomeres.-Darian S in Fightaging

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