CR4 - Aubrey deGrey:
Effect of Weather on Longevity

(Summary by Andrea Feucht)

[mouse CR – why it works]

Antagonistic pleiotropy – smaller organisms live longer in many species; why?

1. fast growth is error-prone
2. those errors can cause cancer
3. fighting cancer accelerates aging

Why aging happens (usual argument):

If you are high on the food chain, you might die of aging rather than being eaten.

However, if there is a famine, your offspring might not live as successfully (and reproduction in general takes a lot of energy, so body resources should be used for survival rather than reproduction

(alternate argument)

1. same 1st reason as above
2. early reproduction means you must grow rapidly early on, which causes rapid aging
3. famine removes the benefits of rapid growth & early reproduction (?)

[other organisms – CR theories]

1. max life extension is at most 14 months, even in dogs which have 11yr lifespan (though their CR was only 25% and it was begun at adulthood…), so their LE was 10%). In insects the life extension is several months (up to 5), even though their lifespan is about 2 months.
2. In mice, 40% extension is common but only 2-3x the real extension of fruit flies, rather than an equivalent % of lifespan.
3. Grasshoppers do diapause (metabolic slow/shutdown) in dry summers
4. Okinawans get about 2 years more than the Japanese mean/max on average, though their health is significantly better

Are insects/small creatures just too different from us and therefore we should ignore those results? Possibly not, if the ‘longevity genes’ are the same across all species, which they could be….

So how can this be extrapolated to humans, if at all?

[MR points out that there are vitamin/mineral deficiencies and poorer healthcare in Okinawans relative to CRONies, and this could be a factor]

THE GRAND THEORY: Is it possible that life extension really can only be a fixed maximum amount and not a percentage of natural lifespan and this is a evolutionary response to periodic famine and weather extremes.

VITAMINS: when we can make a compound internally but it is present in the diet, over time the ability to produce it will die out (Vitamin C)

Predation also raises aging by degenerating anti-aging mechanisms. Long famines enable species to survive them – if less famines, over time the ability to cope/survive the famine will decrease. If at the same time, lifespan is increasing while the probability of famine is the same, CR may still only buy us an extra 2-3 years (the same as when our lifespan was only 30 years).

However:

1. its better than no extension at all
2. Aubrey could be wrong ?
3. Health benefits are still there and are compelling
4. A complementary approach could be on the horizon…

Luigi says, lower birth-weight predisposes one to obesity, heart disease, late life degenerative diseases, etc. So CR while pregnant, intentional or not, is very bad for kidlet.

SENS: Strategies for Engineered Negligible Senescene http://www.sens.org (Lots of ways to deal with effects/markers of aging by direct therapy)

THOUGHTS: Is CR response itself evolved? Evolution is ‘smarter than us’ and obviously there are questions we cannot answer yet. However, even if it is smarter, we have different goals from it, specifically the individual rather than the gene pool of the species at large. We could possibly use evolution’s learned tricks for life extension, such as microbial catabolism of indigestible crap in our bodies (sort of like the oil-slick eating bacteria that have been invented/used). Also, evolution’s only tool is the selection between mutations – we have many more:

1. stem cell therapy
2. gene therapy
3. drug design, supplements
4. site-directed mutagenesis (frankenhumans?)

(reference to “de Grey 2000, Trends in Biotechnology 18:394-399”): Mitochondrial biogenesis is ripe for tweaking, since it is simplistic and easy to induce mutations. [diversion for lots of techie talk about hydrophobicity] Moving the genes from the mitochondria to the nucleus in an unmutated state could be a key therapy, since once in the nucleus those genes are much less likely to mutate.

New technique called protofection….

Conclusion: evolution led us to CR, which could lead us to CR mimetics. However, getting more than what CR can already deliver would be incredibly hard with mimetics only, so we could employ those previously referenced evolutionary tricks to potentially make the CR benefits more wide in scope.

[Josh asks about CoQ10 and its ability to prevent mitochondrial mutations: Aubrey says this is possible; there is another Cambridge researcher who has studied this.]

[Paul asks about SIRT1 and other things like A-L-Cartinine. Aubrey replies that he believes these could hold a lot of promise, especially related to mitochondrial performance in mammals.]