Interestingness: 6
By Michael Rae, in Rejuvenation Research, May 2004, 7(1): 3-8. doi:10.1089/154916804323105026.
This is the first issue where the journal is actually called Rejuvenation Research. It seemed to be a bit of a rebranding to try to disassociate from the general anti-aging crowd, and also when they switched from Michael Fossel to Aubrey de Grey as editor. From the looks of this issue, it's a very positive change.
Most of this short review paper concerns itself with details of genetic profiles of calorie restricted (CR) vs all you want to eat (AD) mice, molecular differences shown, and potential problems with studies regarding CR and CR-mimetics.
There are two interesting bits for me. One is a graph showing proportion increase in lifespan in mice vs number of days under CR. There is a reasonable straight line of best fit, with 45% increase in lifespan reached at around 1800 days on CR.
The other interesting bit is a table showing percentage of increased lifespan on mice when CR was started at weaning (1 month), 12 months (two of these), and 19 months. Mean lifespans for these studies on the CR branch were 43, 37, 33 and 35 months respectively. These represented 130, 119, 113 and 115 percent of control lifespans for each one. Also, they lived 31, 18, 16 and 40 percent longer than controls from the point of starting CR. Those are big numbers for percentage increase from starting point.
(That 19% longer on average vs 18% longer on average of remaining time for the second study seems dodgy to me. It'd seem to imply the mice that did CR were already living 18% longer prior to start of CR).
Sunday, February 19, 2012
Monday, February 13, 2012
Mechanisms of Prolonged Longevity: Mutants, Knock-Outs, and Caloric Restriction
Interestingness: 4
By A Bartke and D Turyn, in the Journal of Anti-Aging Medicine, September 2001, 4(3): 197-203. doi:10.1089/109454501753249966.
Short paper mainly describing the Snell and Ames dwarf mice, some other dwarf mouse (lit/lit), the growth hormone receptor knock-out mouse (GHR-KO), with a small bit comparing them to calorie-restricted mouse. Life span expansion of those is 55%, 25%, 45%, and (from another source since I couldn't see the graph), 30% respectively.
The important bit is a table comparing a lot of attributes across them. Attributes shown: plasma insulin, plasma glucose, sensitivity to insulin, plasma growth hormone, plasma IGF-1, body size, plasma thyroid hormone levels, body core temperature, sexual maturation, fertility, plasma corticosterone and percentage body fat. In all versions of the mice, most of the levels move in the same direction (glucose down, insulin sensitivity up, GH, IGF-1 and body size down, delayed fertility, reduced body temperature). Main difference between CR mice and the others is that the level of corticosterone are up in CR, while they stay at normal levels in the others. Also, body fat is down in CR, normal in the others.
The common elements are more likely to be important for life extension than the ones which are different, although the paper mentions that the raised corticosterone is considered to be a very important part of the effect of CR.
By A Bartke and D Turyn, in the Journal of Anti-Aging Medicine, September 2001, 4(3): 197-203. doi:10.1089/109454501753249966.
Short paper mainly describing the Snell and Ames dwarf mice, some other dwarf mouse (lit/lit), the growth hormone receptor knock-out mouse (GHR-KO), with a small bit comparing them to calorie-restricted mouse. Life span expansion of those is 55%, 25%, 45%, and (from another source since I couldn't see the graph), 30% respectively.
The important bit is a table comparing a lot of attributes across them. Attributes shown: plasma insulin, plasma glucose, sensitivity to insulin, plasma growth hormone, plasma IGF-1, body size, plasma thyroid hormone levels, body core temperature, sexual maturation, fertility, plasma corticosterone and percentage body fat. In all versions of the mice, most of the levels move in the same direction (glucose down, insulin sensitivity up, GH, IGF-1 and body size down, delayed fertility, reduced body temperature). Main difference between CR mice and the others is that the level of corticosterone are up in CR, while they stay at normal levels in the others. Also, body fat is down in CR, normal in the others.
The common elements are more likely to be important for life extension than the ones which are different, although the paper mentions that the raised corticosterone is considered to be a very important part of the effect of CR.
Tuesday, February 7, 2012
Antioxidant Genes, Hormesis, and Demographic Longevity
Interestingness:5
By Robert Arking and Craig Giroux in the Journal of Anti-Aging Medicine, June 2001, pp125-136. doi:10.1089/10945450152466170.
It didn't end up being as interesting as expected, since they skipped/assumed the question of the effect of late-life mortality deceleration or even decrease being real in humans. They mostly work on fruit flies, and that's where most of their data comes from.
I still find overarching theories interesting though, so it was a decent read, even though there isn't much more there to summarise than what was on the abstract.
Their hypothesis can be summarised as follows: there are some stressors that will kick what they call the antioxidant defense system (ADS) and heat shock proteins (hsps) into action and will wipe some "aging" off the body, thus leading to lower mortality. This activation is semi-locked by an epigenetic mechanism, thus leading to a clustering of people with lower mortality separate from the main cluster. They hypothesis that testing young people to see whose ADS get upregulated easiest will tell you which people will leave longer.
One big issue with the paper for me is their evidence that upregulated ADS and hsps lead to longer lifespan. Their data is from fruit flies, but they mention mice, in which just upregulating CuZnSOD (superoxide dismutase) doesn't lead to longer lifespan. In mice, they go by the suggestion that since calorie-restricted mice have upregulated CuZnSOD and catalase, that these two are important reasons of the lifespan extension. I suspect the situation in humans to be even fuzzier.
Another bit of the paper I found interesting is at the beginning where they list possible theories for the decelerated/decreased mortality effect: one, that this is just part of the aging process; second, that this is a predicted effect of the reliability theory I'm fond of by the Gavrilovs (I find these two explanations to be compatible), and third, that the population is genetically heterogenous, so each subsection would have its own Gompertz gradient.
By Robert Arking and Craig Giroux in the Journal of Anti-Aging Medicine, June 2001, pp125-136. doi:10.1089/10945450152466170.
It didn't end up being as interesting as expected, since they skipped/assumed the question of the effect of late-life mortality deceleration or even decrease being real in humans. They mostly work on fruit flies, and that's where most of their data comes from.
I still find overarching theories interesting though, so it was a decent read, even though there isn't much more there to summarise than what was on the abstract.
Their hypothesis can be summarised as follows: there are some stressors that will kick what they call the antioxidant defense system (ADS) and heat shock proteins (hsps) into action and will wipe some "aging" off the body, thus leading to lower mortality. This activation is semi-locked by an epigenetic mechanism, thus leading to a clustering of people with lower mortality separate from the main cluster. They hypothesis that testing young people to see whose ADS get upregulated easiest will tell you which people will leave longer.
One big issue with the paper for me is their evidence that upregulated ADS and hsps lead to longer lifespan. Their data is from fruit flies, but they mention mice, in which just upregulating CuZnSOD (superoxide dismutase) doesn't lead to longer lifespan. In mice, they go by the suggestion that since calorie-restricted mice have upregulated CuZnSOD and catalase, that these two are important reasons of the lifespan extension. I suspect the situation in humans to be even fuzzier.
Another bit of the paper I found interesting is at the beginning where they list possible theories for the decelerated/decreased mortality effect: one, that this is just part of the aging process; second, that this is a predicted effect of the reliability theory I'm fond of by the Gavrilovs (I find these two explanations to be compatible), and third, that the population is genetically heterogenous, so each subsection would have its own Gompertz gradient.
Thursday, February 2, 2012
Telomerase, Telomerase Inhibition, and Cancer
Interestingness: 3
By Ali Ahmed and Trygve O. Tollefsbol, in the Journal of Anti-Aging Medicine, December 2003, 6(4): 315-325. doi:10.1089/109454503323028911.
It didn't turn up to be as interesting as I first thought, but definitely new information regarding telomerase, mostly of the type that I'll forget by tomorrow (ie these genes upregulate this, these downregulate it). In factoid form: telomerase is present in normal human liver cells in an inactive form, c-Myc upregulates telomerase, Mad1 suppresses it.
Telomerase is probably a good thing to test for when looking for cancer since it's very commonly present, ranging from 50-90% of the tests, with the lower numbers mostly seeming from fluids from tests. It is quite rare for it to be expressed in non-cancer cells, outside of the immune system, and even when it is, the numbers are much higher in cancer cells.
Some numbers from the paper: 90% of bladder cancers, 80% of prostate cancers, 69% of renal cancers, 82% of thyroid cancers, 95% of breast cancers. Some studies seem to show a correlation between cancer stage and quantity of telomerase. They also mention correlation between telomerase levels in the tumour and mortality and/or recurrence.
It then talks about methods of downregulating telomerase: transfecting with a dominant negative hTERT gene, antisense on the RNA component of telomerase, and immune hammering of telomerase-positive cells. I didn't know dominant negative genes would be easy to make. They express the usual concerns about what turning off telomerase would do to stem cells and germ cells, but say that both those types are likely to have much longer telomeres than cancer cells.
By Ali Ahmed and Trygve O. Tollefsbol, in the Journal of Anti-Aging Medicine, December 2003, 6(4): 315-325. doi:10.1089/109454503323028911.
It didn't turn up to be as interesting as I first thought, but definitely new information regarding telomerase, mostly of the type that I'll forget by tomorrow (ie these genes upregulate this, these downregulate it). In factoid form: telomerase is present in normal human liver cells in an inactive form, c-Myc upregulates telomerase, Mad1 suppresses it.
Telomerase is probably a good thing to test for when looking for cancer since it's very commonly present, ranging from 50-90% of the tests, with the lower numbers mostly seeming from fluids from tests. It is quite rare for it to be expressed in non-cancer cells, outside of the immune system, and even when it is, the numbers are much higher in cancer cells.
Some numbers from the paper: 90% of bladder cancers, 80% of prostate cancers, 69% of renal cancers, 82% of thyroid cancers, 95% of breast cancers. Some studies seem to show a correlation between cancer stage and quantity of telomerase. They also mention correlation between telomerase levels in the tumour and mortality and/or recurrence.
It then talks about methods of downregulating telomerase: transfecting with a dominant negative hTERT gene, antisense on the RNA component of telomerase, and immune hammering of telomerase-positive cells. I didn't know dominant negative genes would be easy to make. They express the usual concerns about what turning off telomerase would do to stem cells and germ cells, but say that both those types are likely to have much longer telomeres than cancer cells.
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