18 replies to this topic

[InquilineKea]

http://www.physorg.c...lues-aging.html

Quite interesting, I must say. What prevents these animals from getting cancer, anyways? There's a site (http://www.agelessanimals.org/) about rockfish, and VERY similarly related rockfish have DRAMATICALLY different lifespans. And it appears to be all due to telomerase

The thing is, there are some things that cannot be stopped with age, even if you maintain your telomere length. Won't your lysosomes still fill up with junk? But how much does this really matter? Do mouse lysosomes still fill up with junk 40 times faster than humans, even though their metabolisms definitely aren't 40 times longer?

I mean, eventually, you'll still have to find a way to correct for nuclear DNA damage and mitochondrial DNA damage. But the mechanisms of those take much longer, and they do not necessarily imply a maximum lifespan (since some people will be luckier than others - mutation is chance)

BUT - we also know from the article that reducing IGF-1 will nearly eliminate the chances of cancer. So *here's* a possible recipe: cut off IGF-1 through a near-vegan diet, and THEN apply telomerase. Might that actually work? =D

Edited by InquilineKea, 04 March 2011 - 03:10 PM.

[1101]

Generally animals that live for a very long have some sort of reproductive disadvantage. The rougheye rockfish (one of the animals listed) lives at extreme depths over a wide range of territory making it difficult to find a mate. By living longer it increases it increases its likelihood of reproducing. When you think about it humans, who are fairly long lived, also have a reproductive disadvantage in that it takes well over a decade to raise their offspring to reproductive maturity. By living longer the original parents are able to ensure that their offspring live to pass on their genes.

Interestingly the rougheye is carnivorous, so I doubt your vegan theory has any merit. Maybe its telomerase induced youthful immune system is enough to ward off cancer. As for correcting DNA, that's easy. Just kill off the cells that stop doing what they're supposed to (ie those that have so many mutations in a given gene that it stops functioning correctly/becomes cancerous).

[InquilineKea]

Interestingly the rougheye is carnivorous, so I doubt your vegan theory has any merit. Maybe its telomerase induced youthful immune system is enough to ward off cancer. As for correcting DNA, that's easy. Just kill off the cells that stop doing what they're supposed to (ie those that have so many mutations in a given gene that it stops functioning correctly/becomes cancerous).

Hm, well, the rockfish might have other ways of decreasing its IGF-1 levels. Carnivores certainly have all sorts of mechanisms to prevent "over-responding" to all the protein in their diet.

[Phil Goetz]

The link between aging and IGF1 is more robust: There is a strong correlation between aging and growth. This appears to be mediated largely through mTOR (mammalian target of rapamycin). mTOR activation promotes transcription, synthesis, growth, and repair. Possibly every known method of life extension (probably including at least rapamycin, caloric restriction, and dwarfism in rodents) works by inhibiting mTOR, or by up-regulating PGC1-alpha, which increases production of mitochondria. IGF1 is just one up-regulator of mTOR, IIRC.

mTOR, PGC-1a, and SIRT1 are all linked together in confusing ways. It is not known whether the life-extending effect of these genes can be separated from anti-growth, anti-repair, muscle-wasting pathways.

Edited by Phil Goetz, 12 March 2011 - 06:57 AM.

[VidX]

Well only LE we'd really like to experience is that of Metshusellah flies (if to talk about working ways to extend LS). They doesn't not have to take trade-offs and still live 5-6 times longer, more rubust, strionger, with a better reproduction, etc...

[Cameron]

eusocial insects, where different epigenetics via diet can lead genetically identical organisms to experience aging at different rate worker vs queen, could shed some light on aging as the difference is merely gene expression and some eusocial queens are considered to exhibit negligible senescence while the genetically identical worker ages.

Edited by Cameron, 12 March 2011 - 02:50 PM.

[Phil Goetz]

You can't infer that telomerase differences are causal. Telomerase extends cell life while increasing the risk of cancer. The optimal amount of telomerase increases as cancer risk decreases. Organisms that are long-lived evolve powerful defenses against cancer, thus increasing their optimal telomerase levels.

[VidX]

eusocial insects, where different epigenetics via diet can lead genetically identical organisms to experience aging at different rate worker vs queen, could shed some light on aging as the difference is merely gene expression and some eusocial queens are considered to exhibit negligible senescence while the genetically identical worker ages.

That is actually VERY VERY interesting and relevant.

[treonsverdery]

Perhaps if they cultured fish tissue at different temperatures they could see if the hayflick effect varied

I don't actually remember if the hayflick effect where cytes divide a certain number of times is linked to relomeres or not
anyway these fish live at cool temperatures looking at the genes active at different temperatures as well as the effect on the number of cytodivisions could isolate particular longevity genes

http://www.ncbi.nlm....flick telomeres

[nowayout]

So what ARE the purported clues alluded to in the title?

Specifically, what mechanisms, if any, have been identified from studying these animals? One would think an article with that title would discuss this. I can find nothing online.

Edited by viveutvivas, 02 April 2011 - 02:51 PM.

[Immiye]

http://green.yahoo.c...tal-animal.html

This animal is said to have no life span. It can in theory, without any outside influence live forever.

[DaffyDuck]

Telomerase extends cell life while increasing the risk of cancer.

Telomerase is not an Oncogene.

Do you know of more recent studies that prove this paper to be incorrect?

[Dmitri]

Telomerase extends cell life while increasing the risk of cancer.

Telomerase is not an Oncogene.

Do you know of more recent studies that prove this paper to be incorrect?

I don't think that's what he's saying; what he means is that the longer cells live and the more they divide the more mistakes they are bound to make which could eventually lead to Cancer.

[Methos000]

Possibly the queen's somatic cells express telomerase, while the worker's do not. I don't agree with the poster who stated that high levels of telomerase increase cancer. The studies I've seen don't support his conclusion. Now, cancer may increase the number of somatic cells that express telomerase, but telomerase didn't cause the cancer. Long telomeres are known to be preventative of cancer.

eusocial insects, where different epigenetics via diet can lead genetically identical organisms to experience aging at different rate worker vs queen, could shed some light on aging as the difference is merely gene expression and some eusocial queens are considered to exhibit negligible senescence while the genetically identical worker ages.

That is actually VERY VERY interesting and relevant.

[DorianGrey]

Telomerase enables cancer cells to reproduce beyond the Hayflick limit. The issue is that if you allow proto-oncogene cells to divide longer by shifting the Hayflick limit a bit, you are more likely to get a mutation over time that leads to cancer. IMO this becomes more critical with age or people with poor health (chronic inflammation, weak immune system) because the body can no longer fight back against those rogue cells. My conclusion is that you should use Telomerase activators while you are not too old and still healthy, then a mild stimulation shouldn't really put you at risk. On the other hand, if your life expectancy is short anyway and cancer is not the issue, taking a risk may be acceptable (Alzheimer; Stroke etc).
There's this anecdotal evidence of that guy on TA-65 who got prostate cancer at 60. I suppose 55-75 years is exactly the risky time, when you still have quality time left but health already deteriorates.

Edited by DorianGrey, 11 May 2013 - 12:56 AM.

[nowayout]

Telomerase inducers do not extend mouse lifespan.

http://healthactivat...ephen-spindler/

[DorianGrey]

Thanks for the link in general, but I haven't seen the actually study there. Is it mentioned in the talk during the video? If you look up the knowledge on Telomers even on Wikipedia, there are studies that Telomerase activation does extend the life span of mice, so I guess there might be a flawed study design. E.g., in real life your immune system fights quite a number of bugs, whilst in an aseptic lab environment that might not be the case.

[nowayout]

Thanks for the link in general, but I haven't seen the actually study there. Is it mentioned in the talk during the video? If you look up the knowledge on Telomers even on Wikipedia, there are studies that Telomerase activation does extend the life span of mice, so I guess there might be a flawed study design. E.g., in real life your immune system fights quite a number of bugs, whilst in an aseptic lab environment that might not be the case.

It is new work that is not yet published. I would recommend watching the whole clip.

Stephen Spindler is well respected for setting very exacting standards for screening compounds for life extension. He talks about how they made sure that the telomerase inducer they used actually was absorbed properly and did what it was expected to do on the microbiological level. Yet it did not extend the lifespan of the mice.

I am not sure how large the previous studies were and what the standards were. One problem Spindler mentions with a lot of prior studies is that many supplements make mice feel bad or make the food taste bad, so they eat less, meaning they are effectively on CR. Many studies basically should be thrown out because they didn't control for this. Maybe that is the flaw in the studies you mention on Wikipedia.

This paper by him claims to describe the problem and confounders with the majority of existing rodent life extension screens, maybe including the ones you mention. Full text is here http://www.crsociety...h-and-lifespan/

EDIT: Actually the studies I see cited on Wikipedia are all to do with gene engineering, not telomerase-inducing supplements.

Edited by viveutvivas, 11 May 2013 - 09:22 PM.

[DorianGrey]

EDIT: Actually the studies I see cited on Wikipedia are all to do with gene engineering, not telomerase-inducing supplements.
tr
You are right, I didn't mention that but have observed that as well. Gene engineering is a lot less guess work but not practical for common use (what I am looking for) at this time.

I have to admit I didn't get to watching the entire video yet, but will do before my next post in this thread.

For now let's agree
- Telomer length is established to correlate with life span in men and mice (shown via genetic studies, TERT mutations etc)
- Some inducers work in cell culture but it's hard to show they work in vivo
- Studies in mice aren't always well designed and there are some effects that play a role in humans (e.g. immune system isn't that similar), so I wouldn't conclude from one negative study that all known inducers never work. There are so many factors, the most basic are what inducer was used, when was induced and for how long, what was the dosing per kg etc. And the kind of mice may also play a role, like the TERT or SIRT gene sequence.
1.) If bioavailability in different cell tissues wasn't shown, it really diminishes the value of a study.
2.) Telomer length in different cell types should have been evaluated near the end of the study, better even in the same subjects at start and end.
=> When a study confirms telomers have been preserved (or lengthened) in the induced mouse strata but not in the placebo strata, but both die at the same age for similar reasons, then that would be indeed remarkable.