By the abstracts:
"Watch Your Notch: A Link Between Aging and Stem Cell Fate?" is about Notch being sufficient to activate satellite stem cells and regenerate muscle in old mice. Maybe. Want to read the rest.
"Why Use Telomerized Cells for Organ Transplantation?". I don't know what this one is about aside from the title. First page is a description of telomeres and telomerase.
"Tissue Engineering and Regenerative Medicine: Concepts for Clinical Application ". A review of advances in regenerative medicine, by which I assume he means tissue regeneration. Lots of citations.
"Depigmentation and Rejuvenation Effects of Kinetin on the Aged Skin of Hairless Descendants of Mexican Hairless Dogs". Something about kinetin, a cell reproduction inducer, clearing melanin granules and improving superficial signs of skin youth in old dogs.
"Hormetic Mechanisms of Anti-Aging and Rejuvenating Effects of Repeated Mild Heat Stress on Human Fibroblasts in Vitro". Repeated mild heat stress produces some supposedly good results in the protein profiles of fibroblasts.
"Someone's Knocking on the Laboratory Door". Didn't get to the meat.
"A New Age for Aging? Ethical Questions, Scientific Insights, and Societal Outcomes". Ethics.
"Immunosenescence: What is It and What Can Be Done About It?". A summary of a session on immunosenescence at the British Society for Immunology 2003 conference. One talk on T cell disregulation and on the influence of cytomegalovirus on creating useless CD8 cells that hang around. Want to read the rest.
Friday, June 1, 2012
Sunday, February 19, 2012
It's Never Too Late: Calorie Restriction is Effective in Older Mammals
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).
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).
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.
Tuesday, January 31, 2012
December 2003 issue
Still mostly reading the abstracts. I managed to get the only paper I would have read out of these from the author's site, so it isn't as big a loss as usual, but I would still like to read the full literature review and dissertations columns.
"Telomeres Shorten with Age in Rat Cerebellum and Cortex in vivo". It seems like they measured telomere length and telomerase activity in 21 day old and 5 month old rat cortices and cerebellums. Shorter telomeres in older. Shorter in cortex than cerebellum. Higher telomerase in older than younger, and in cerebellums than in cortices. All this shortening presumed by authors to be from microglia since only replicating cell in brain. Very well cited paper. Not that interesting to me, but all things telomere seemed to be popular then.
"Will Human Life Expectancy Quadruple in the Next Hundred Years? Sixty Gerontologists Say Public Debate on Life Extension Is Necessary". Survey of gerontologists predicting future life exptectancy.
"Telomerase, Telomerase Inhibition, and Cancer". This one sounded interesting, and I found it on the author's page, so separate post for it.
"Reduced Level of Serum Thiols in Patients with a Diagnosis of Active Disease". Lower serum protein thiols in sick people than in healthy people. Implied lower oxidation in healthy.
"Soy-Induced Brain Atrophy?". Maybe soy lowers BDNF in males.
The literature review column looks at a paper analysing people with skin grafts sourced from their own body and cultured (autologous skin grafts), and seeing shorter telomeres in their grafted bits than in their intact bits. Review mentions that there were only four patients and controls (intact skin) was taken from only two of them. Still, it'd make sense if it was the case. (UPDATE: found the full review. They also look at a paper that finds a negative correlation between telomere length shortening rate in birds and their lifespan)
The first page of the dissertations section had the summary for a thesis on the effect of fitness on the hypothalamic-pituitary-adrenal axis on women, and another for automated brain segmentation from MRI images to measure brain bits as they age, in monkeys.
"Telomeres Shorten with Age in Rat Cerebellum and Cortex in vivo". It seems like they measured telomere length and telomerase activity in 21 day old and 5 month old rat cortices and cerebellums. Shorter telomeres in older. Shorter in cortex than cerebellum. Higher telomerase in older than younger, and in cerebellums than in cortices. All this shortening presumed by authors to be from microglia since only replicating cell in brain. Very well cited paper. Not that interesting to me, but all things telomere seemed to be popular then.
"Will Human Life Expectancy Quadruple in the Next Hundred Years? Sixty Gerontologists Say Public Debate on Life Extension Is Necessary". Survey of gerontologists predicting future life exptectancy.
"Telomerase, Telomerase Inhibition, and Cancer". This one sounded interesting, and I found it on the author's page, so separate post for it.
"Reduced Level of Serum Thiols in Patients with a Diagnosis of Active Disease". Lower serum protein thiols in sick people than in healthy people. Implied lower oxidation in healthy.
"Soy-Induced Brain Atrophy?". Maybe soy lowers BDNF in males.
The literature review column looks at a paper analysing people with skin grafts sourced from their own body and cultured (autologous skin grafts), and seeing shorter telomeres in their grafted bits than in their intact bits. Review mentions that there were only four patients and controls (intact skin) was taken from only two of them. Still, it'd make sense if it was the case. (UPDATE: found the full review. They also look at a paper that finds a negative correlation between telomere length shortening rate in birds and their lifespan)
The first page of the dissertations section had the summary for a thesis on the effect of fitness on the hypothalamic-pituitary-adrenal axis on women, and another for automated brain segmentation from MRI images to measure brain bits as they age, in monkeys.
Saturday, January 28, 2012
September 2003 issue
Another one mostly by the abstracts. A couple of interesting things in this one.
"An Ethical Assessment of Anti-Aging Medicine". Ethics.
"A Telomere-Binding Protein (TRF2/MTBP) from Mouse Nuclear Matrix with Motives of an Intermediate Filament-Type Rod Domain". telomere membrane binding protein = telomere repeat factor 2 = (?) protein that binds telomere to nuclear membrane.
"Apparent Induction of Partial Thymic Regeneration in a Normal Human Subject: A Case Report". Growth hormone plus DHEA maybe made the thymus in one person larger and with a larger active region. Rare growth hormone article that I'd be interested in reading.
Report on a meeting for the association and politics for life science. Sounds like mainly ethics.
Report on the 10th congress of the International Association of Biomedical Gerontology, which also seemed to function as a SENS meeting. Found the summary of highlights on the net. Impossible to summarise, but LOTS of interesting papers presented.
Review of the books "The iron factor of aging: why do americans age faster?" which seems to suggest that iron supplementation helps (!?) and one on ethics.
A review of a paper that looks at the link between telomere length and telomerase activity in glioblastomas.
The dissertations section, or at least the first page which I can see, looks at a thesis that compares the hydrogen peroxide production in a bat, a shrew and a mouse, and comes up with them all having similar lifetime free radical production per mitochondrial protein. It also says free radical production in the bat is higher in youth than in old age, which the author says contradicts the free radical theory of aging. She suggests this is due to selection of efficient mitochondria during the lifetime. As far as I understand it, this contradicts de Grey's version of the FRTA too. The thesis was easy to find online from the university's site but I haven't read it properly yet. Interesting nevertheless. The thesis is titled "Aging and mitochondrial efficiency in the little brown bat, Myotis Lucifugus".
The second dissertation mentioned was about the effects of HIV on CD8+ T cell senescence.
"An Ethical Assessment of Anti-Aging Medicine". Ethics.
"A Telomere-Binding Protein (TRF2/MTBP) from Mouse Nuclear Matrix with Motives of an Intermediate Filament-Type Rod Domain". telomere membrane binding protein = telomere repeat factor 2 = (?) protein that binds telomere to nuclear membrane.
"Apparent Induction of Partial Thymic Regeneration in a Normal Human Subject: A Case Report". Growth hormone plus DHEA maybe made the thymus in one person larger and with a larger active region. Rare growth hormone article that I'd be interested in reading.
Report on a meeting for the association and politics for life science. Sounds like mainly ethics.
Report on the 10th congress of the International Association of Biomedical Gerontology, which also seemed to function as a SENS meeting. Found the summary of highlights on the net. Impossible to summarise, but LOTS of interesting papers presented.
Review of the books "The iron factor of aging: why do americans age faster?" which seems to suggest that iron supplementation helps (!?) and one on ethics.
A review of a paper that looks at the link between telomere length and telomerase activity in glioblastomas.
The dissertations section, or at least the first page which I can see, looks at a thesis that compares the hydrogen peroxide production in a bat, a shrew and a mouse, and comes up with them all having similar lifetime free radical production per mitochondrial protein. It also says free radical production in the bat is higher in youth than in old age, which the author says contradicts the free radical theory of aging. She suggests this is due to selection of efficient mitochondria during the lifetime. As far as I understand it, this contradicts de Grey's version of the FRTA too. The thesis was easy to find online from the university's site but I haven't read it properly yet. Interesting nevertheless. The thesis is titled "Aging and mitochondrial efficiency in the little brown bat, Myotis Lucifugus".
The second dissertation mentioned was about the effects of HIV on CD8+ T cell senescence.
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