By the abstracts:
"Are Expanded Polyglutamine Proteins a Proteasome Substrate?". Enquiry into whether the accumulation of polyglutamine aggregation that causes neurodegeneration is due to non-working proteasome function.
"Lifelong Aspirin Supplementation as a Means to Extending Life Span". Protocol proposal and rational for the experiment of what they suggest on the title. Not the results of such an experiment. Seems to focus mostly on the anti-inflammatory properties. Maybe interesting, although I would rather read the paper on the results of the experiment.
"Is Carnosine a Naturally Occurring Suppressor of Oxidative Damage in Olfactory Neurones?". What is says on the title.
A meeting report on "The 8th International Symposium on the Maillard Reaction (Charleston, South Carolina, August 28 to September 1, 2004)". Maillard reaction = glycation = non-enzimatic glycosylation. Didn't get to the meat, but I always like meeting reports.
A review of the book "Aging, Death, and Human Longevity: A Philosophical Inquiry" by Christine Overall (the book, not the review). Philosophy.
A review of the book "Aging, Death, and Human Longevity: A Philosophical Inquiry" by Gina Smith. Popular science.
Overall, I'm not as upset as usual at not having the papers for this one.
Monday, September 3, 2012
Sunday, September 2, 2012
Premature ageing in mice expressing defective mitochondrial DNA polymerase
Interestingness: 8
By Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT, Bruder CE, Bohlooly-Y M, Gidlöf S, Oldfors A, Wibom R, Törnell J, Jacobs HT and Larsson NG, in Nature, on the 27th of May, 2004. 429(6990):417-23. http://www.ncbi.nlm.nih.gov/pubmed/15164064
This isn't a paper from Rejuvenation Research, but since it was referenced in the last post, I read it and found it very interesting, notwithstanding de Grey's comments on it not being as interesting as it seems.
They created mice with a mutant version of the mtDNA polymerase instead of the regular version, that resulted in 3-5 times the usual number of mutations in their mtDNA and many more mtDNA deletions (30% less full-length mtDNA than wild type). Mutations were uniform throughout the whole mtDNA. The method of creating these mutant mice is interesting enough, but I won't describe that here.
These mice live for about a year. They have much smaller testes by the 3 month mark. They then get some fucked-up looking back deformations (kyphosis), start losing their hair, losing weight, become anaemic (with larger than usual and paler red blood cells), and get enlarged spleens by around the six-month mark. They develop osteoporosis and enlarged left ventricles at around the 9 month mark.
If de Grey's explanation is right then it's not significant, but if he is wrong, then mtDNA mutations become more important.
By Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT, Bruder CE, Bohlooly-Y M, Gidlöf S, Oldfors A, Wibom R, Törnell J, Jacobs HT and Larsson NG, in Nature, on the 27th of May, 2004. 429(6990):417-23. http://www.ncbi.nlm.nih.gov/pubmed/15164064
This isn't a paper from Rejuvenation Research, but since it was referenced in the last post, I read it and found it very interesting, notwithstanding de Grey's comments on it not being as interesting as it seems.
They created mice with a mutant version of the mtDNA polymerase instead of the regular version, that resulted in 3-5 times the usual number of mutations in their mtDNA and many more mtDNA deletions (30% less full-length mtDNA than wild type). Mutations were uniform throughout the whole mtDNA. The method of creating these mutant mice is interesting enough, but I won't describe that here.
These mice live for about a year. They have much smaller testes by the 3 month mark. They then get some fucked-up looking back deformations (kyphosis), start losing their hair, losing weight, become anaemic (with larger than usual and paler red blood cells), and get enlarged spleens by around the six-month mark. They develop osteoporosis and enlarged left ventricles at around the 9 month mark.
If de Grey's explanation is right then it's not significant, but if he is wrong, then mtDNA mutations become more important.
Monday, August 27, 2012
Mitochondrial Mutations in Mammalian Aging: An Over-Hasty About-Turn?
Interestingness: 7
By Aubrey DNJ De Grey, in Rejuvenation Research, Northern Autumn 2004, 7(3): 171-174. doi:10.1089/rej.2004.7.171.
A short piece of commentary trying to raise the profile of, I think, this paper: "Construction of transgenic mice with tissue-specific acceleration of mitochondrial DNA mutagenesis", by Zhang D et al (http://www.ncbi.nlm.nih.gov/pubmed/11031098), but mainly about lowering the importance of "Premature ageing in mice expressing defective mitochondrial DNA polymerase" by Trifunovic A et al (http://www.ncbi.nlm.nih.gov/pubmed/15164064 ) . I haven't read the former, and I've only read the latter just now (separate post).
Zhang's paper is about mice with a mutant mtDNA polymerase which produced more errors, but is only activated in the heart, and only after birth. Trifunovic's paper is a similar concept but they made it active in all tissue. Also, while in Trifunovic's experiment they modified the built-in version of the mtDNA polymerase, I am not sure if that is what was done in Zhang's version, or if they just added a second copy.
The results of the modifications are that in Zhang's, the mice get cardiomyopathy, while Trifunovic's mice get fucked up all over and die at around the year mark.
de Grey's objection to the importance of Trifunovic's paper is that the effects seem to hit mainly tissue undergoing rapid replication (the spleen, the skin, testes and blood), and that the heart issues were a compensation mechanism for the anaemia. His claim is that this failure of rapidly replicating tissue cannot cause a shortening of lifespan since the failing cells can just be replaced by the replication of the still-good cells, unless the cells are failing faster than they can be replaced, which is what he thinks is happening during the experiment.
It would be good if he'd have addressed specifically the coincidence that in both cases the mice suffered from enlarged hearts, but according to him due to separate causes (ie is it a coincidence?). I don't know the timing of the cardiomyopathy in the Zhang experiment though, so it might have come around much later and there might not be anything to address.
By Aubrey DNJ De Grey, in Rejuvenation Research, Northern Autumn 2004, 7(3): 171-174. doi:10.1089/rej.2004.7.171.
A short piece of commentary trying to raise the profile of, I think, this paper: "Construction of transgenic mice with tissue-specific acceleration of mitochondrial DNA mutagenesis", by Zhang D et al (http://www.ncbi.nlm.nih.gov/pubmed/11031098), but mainly about lowering the importance of "Premature ageing in mice expressing defective mitochondrial DNA polymerase" by Trifunovic A et al (http://www.ncbi.nlm.nih.gov/pubmed/15164064 ) . I haven't read the former, and I've only read the latter just now (separate post).
Zhang's paper is about mice with a mutant mtDNA polymerase which produced more errors, but is only activated in the heart, and only after birth. Trifunovic's paper is a similar concept but they made it active in all tissue. Also, while in Trifunovic's experiment they modified the built-in version of the mtDNA polymerase, I am not sure if that is what was done in Zhang's version, or if they just added a second copy.
The results of the modifications are that in Zhang's, the mice get cardiomyopathy, while Trifunovic's mice get fucked up all over and die at around the year mark.
de Grey's objection to the importance of Trifunovic's paper is that the effects seem to hit mainly tissue undergoing rapid replication (the spleen, the skin, testes and blood), and that the heart issues were a compensation mechanism for the anaemia. His claim is that this failure of rapidly replicating tissue cannot cause a shortening of lifespan since the failing cells can just be replaced by the replication of the still-good cells, unless the cells are failing faster than they can be replaced, which is what he thinks is happening during the experiment.
It would be good if he'd have addressed specifically the coincidence that in both cases the mice suffered from enlarged hearts, but according to him due to separate causes (ie is it a coincidence?). I don't know the timing of the cardiomyopathy in the Zhang experiment though, so it might have come around much later and there might not be anything to address.
Issue 3, 2004
By the abstracts:
"Regulation of Murine Telomere Length via Rtel". What the title says. Rtel being a DNA helicase-like protein gene. Hadn't heard about it.
"Mitochondrial Mutations in Mammalian Aging: An Over-Hasty About-Turn?". This seems, from the abstract, to be de Grey chastising the community both for ignoring mtDNA mutations and then for changing their mind too easily due to a study of a mouse with accelerated mtDNA mutations in which it had aging-like issues. Sounds interesting.
"The Interdependence of Skin Aging, Skin Cancer, and DNA Repair Capacity: A Novel Perspective with Therapeutic Implications". Review of effects of UV light on skin DNA, and repair against those effects.
"Rejuvenation of Visual Functions in Older Adult Drivers and Drivers with Cataract During a Short-Term Administration of N-Acetylcarnosine Lubricant Eye Drops". RCT of N-acetylcarnosine on 130 people, half of them with cataracts. They seem to think it works at reducing glare sensitivity.
"Paradoxes of Non-Trivial Gene Networks: How Cancer-Causing Mutations Can Appear to Be Cancer-Protective". Model paper supposedly showing how certain alleles that seem onco-protective could actually be onco-causal. Maybe interesting.
Commentary on "A Policy Analysis of Funding for Ambitious Interventional Gerontology: The Possibility of Rejuvenation Research at the National Institute on Aging" about how to get rejuvenation research structured/funded under the National Institute of Aging.
"Science and Politics: World Events Intensify Stem Cell Debate". Some supposed-to-be report about the First International Stem Cell Action Conference, but which seems to be commentary on the US political situation on stem cell research.
A report of the "Regenerate 2004: Tissue Engineering the Human Body, June 10–12, 2004, Seattle" meeting. These are always fun to read. A bit of a downer in that the topics discussed sound very similar to what I keep reading about currently.
"Regulation of Murine Telomere Length via Rtel". What the title says. Rtel being a DNA helicase-like protein gene. Hadn't heard about it.
"Mitochondrial Mutations in Mammalian Aging: An Over-Hasty About-Turn?". This seems, from the abstract, to be de Grey chastising the community both for ignoring mtDNA mutations and then for changing their mind too easily due to a study of a mouse with accelerated mtDNA mutations in which it had aging-like issues. Sounds interesting.
"The Interdependence of Skin Aging, Skin Cancer, and DNA Repair Capacity: A Novel Perspective with Therapeutic Implications". Review of effects of UV light on skin DNA, and repair against those effects.
"Rejuvenation of Visual Functions in Older Adult Drivers and Drivers with Cataract During a Short-Term Administration of N-Acetylcarnosine Lubricant Eye Drops". RCT of N-acetylcarnosine on 130 people, half of them with cataracts. They seem to think it works at reducing glare sensitivity.
"Paradoxes of Non-Trivial Gene Networks: How Cancer-Causing Mutations Can Appear to Be Cancer-Protective". Model paper supposedly showing how certain alleles that seem onco-protective could actually be onco-causal. Maybe interesting.
Commentary on "A Policy Analysis of Funding for Ambitious Interventional Gerontology: The Possibility of Rejuvenation Research at the National Institute on Aging" about how to get rejuvenation research structured/funded under the National Institute of Aging.
"Science and Politics: World Events Intensify Stem Cell Debate". Some supposed-to-be report about the First International Stem Cell Action Conference, but which seems to be commentary on the US political situation on stem cell research.
A report of the "Regenerate 2004: Tissue Engineering the Human Body, June 10–12, 2004, Seattle" meeting. These are always fun to read. A bit of a downer in that the topics discussed sound very similar to what I keep reading about currently.
Sunday, August 26, 2012
Telomeres and Telomerase: A Modern Fountain of Youth?
Interestingness: 3
By João Pedro de Magalhães and Olivier Toussaint, in Rejuvenation Research, July 2004, 7(2): 126-133. doi:10.1089/1549168041553044.
Not as much new material in this short paper as I expected, probably because I've read quite a bit on the topic since this was published. Interesting bits picked out:
In summary, they think that telomerase might be beneficial for specific diseases but they doubt it'll turn out to be an anti-aging agent.
By João Pedro de Magalhães and Olivier Toussaint, in Rejuvenation Research, July 2004, 7(2): 126-133. doi:10.1089/1549168041553044.
Not as much new material in this short paper as I expected, probably because I've read quite a bit on the topic since this was published. Interesting bits picked out:
- No correlation between maximum number of cell replications (cumulative population doublings) and age (post birth). (I have the vague recollection of some paper saying the opposite)
- No connection between mean telomere length and mammalian aging. (I think they mean across species, the species with the longer telomeres don't live any longer).
- Telomere length in vivo has very high variability
In summary, they think that telomerase might be beneficial for specific diseases but they doubt it'll turn out to be an anti-aging agent.
Issue 2, 2004
By the abstracts:
"Inter-Species Therapeutic Cloning: The Looming Problem of Mitochondrial DNA and Two Possible Solutions". Title seems like a good summary.
"Catecholamines and Protein Deposition in Parkinson's and Alzheimer's Disease: Old Medicine, New Targets". Didn't get to the meat. Catecholamines, wiki says, are compounds that have a catechol, which is a benzene with two hydroxil groups attached. eg epinephrine, dopamine.
"A Reproducible Laser-Wounded Skin Equivalent Model to Study the Effects of Aging In Vitro". Trying to create a model of partial wounds on skin (by partial meaning not through the whole thing). They like the look of the wounds produced by a low powered excimer laser (excimer lasers emit UV, wiki tells me).
"Selective Pressure for a Decreased Rate of Asymmetrical Divisions Within Stem Cell Niches May Contribute to Age-Related Alterations in Stem Cell Function". The abstract claims that there is a selection pressure for stem cells to reproduce symmetricaly, and thus produce two stem cells, and probably cancer, but this paper is about a second independent pressure against asymmetrical division of stem cells. Sounds interesting.
"Telomeres and Telomerase: A Modern Fountain of Youth?". Discusses whether telomerase will be used for anti-aging therapies. They think not. Want to read the rest, or, more likely, an updated version of it.
"Aging Theories of Primary Osteoarthritis: From Epidemiology to Molecular Biology". Seems to be a review paper on osteoarthritis. Very well cited.
A review of the book "Cells, Aging, and Human Disease" by Michael Fossel
"Inter-Species Therapeutic Cloning: The Looming Problem of Mitochondrial DNA and Two Possible Solutions". Title seems like a good summary.
"Catecholamines and Protein Deposition in Parkinson's and Alzheimer's Disease: Old Medicine, New Targets". Didn't get to the meat. Catecholamines, wiki says, are compounds that have a catechol, which is a benzene with two hydroxil groups attached. eg epinephrine, dopamine.
"A Reproducible Laser-Wounded Skin Equivalent Model to Study the Effects of Aging In Vitro". Trying to create a model of partial wounds on skin (by partial meaning not through the whole thing). They like the look of the wounds produced by a low powered excimer laser (excimer lasers emit UV, wiki tells me).
"Selective Pressure for a Decreased Rate of Asymmetrical Divisions Within Stem Cell Niches May Contribute to Age-Related Alterations in Stem Cell Function". The abstract claims that there is a selection pressure for stem cells to reproduce symmetricaly, and thus produce two stem cells, and probably cancer, but this paper is about a second independent pressure against asymmetrical division of stem cells. Sounds interesting.
"Telomeres and Telomerase: A Modern Fountain of Youth?". Discusses whether telomerase will be used for anti-aging therapies. They think not. Want to read the rest, or, more likely, an updated version of it.
"Aging Theories of Primary Osteoarthritis: From Epidemiology to Molecular Biology". Seems to be a review paper on osteoarthritis. Very well cited.
A review of the book "Cells, Aging, and Human Disease" by Michael Fossel
Friday, June 1, 2012
Rest of issue 1, 2004
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.
"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.
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.
Thursday, January 26, 2012
June 2003
Only reading abstracts.
"Telomere-Binding TRF2/MTBP Localization during Mouse Spermatogenesis and Cell Cycle of the Mouse Cells L929". Spot the telomere and the telomere membrane binding protein. Maybe I should be interested in this one, but don't seem to be.
A review of Werner's and Hutchinson-Gilford progerias.
A review of "Geriatric Medicine: an evidence based approach". Supposedly good.
An interesting new section called Dissertations, where they publish abstracts of thesis that are relevant. Very cool idea. I can only see the first one and a half. One about the roles of telomere-binding proteins have in telomere function in yeast, another one about targeting telomere and telomerase for cancer treatment, maybe mainly with a combination of paclitaxel, which damages telomeres, and AZT, which inhibits telomerase.
The review of the literature looks at a paper about the relationship between telomere length and Alzheimer's, stroke, and vascular dementia patients. I can't tell what happened since the results are on the second page, but going by the title of the paper, vascular dementia patients probably have shorter telomeres. (PS: actually, the paper is available in full, and yes, people with vascular dementia seem to have shorter telomeres on their peripheral blood mononuclear cells)
"Telomere-Binding TRF2/MTBP Localization during Mouse Spermatogenesis and Cell Cycle of the Mouse Cells L929". Spot the telomere and the telomere membrane binding protein. Maybe I should be interested in this one, but don't seem to be.
A review of Werner's and Hutchinson-Gilford progerias.
A review of "Geriatric Medicine: an evidence based approach". Supposedly good.
An interesting new section called Dissertations, where they publish abstracts of thesis that are relevant. Very cool idea. I can only see the first one and a half. One about the roles of telomere-binding proteins have in telomere function in yeast, another one about targeting telomere and telomerase for cancer treatment, maybe mainly with a combination of paclitaxel, which damages telomeres, and AZT, which inhibits telomerase.
The review of the literature looks at a paper about the relationship between telomere length and Alzheimer's, stroke, and vascular dementia patients. I can't tell what happened since the results are on the second page, but going by the title of the paper, vascular dementia patients probably have shorter telomeres. (PS: actually, the paper is available in full, and yes, people with vascular dementia seem to have shorter telomeres on their peripheral blood mononuclear cells)
Tuesday, January 24, 2012
March 2003, sadly without access
I'm still only reading the abstracts, but in this one there were two that sounded interesting, but I couldn't find them around.
"Early Programming of Adult Longevity: Demographic and Experimental Studies". They look at 100,000 people that died in the 1990s in Kiev and see a "strong association" between the month of the year they were born in and longevity, with the lowest longevity for people born April to July, and highest around December. The July and December low/high agree with what the Gavrilovs found in their studies of aristocratic families (see http://readingrejuvenationresearch.blogspot.com/2011/02/season-of-birth-and-human-longevity.html ) . On a seemingly completely unrelated study, they look at the lifespan of fruit flies and see them living longer when they are irradiated with low doses of radiation. Their hypothesis is that both effects, and many other anti-aging treatments, are due to the hormetic effect (ie response to low level stressor). Would like to read this one.
"Neuroprotective, Anti-Apoptotic Effects of Apomorphine". Looks at apomorphine's effects on the brain, with the possible focus on Parkinson's.
"The Role of Somatic and Germline Mutations in Aging and a Mutation Interaction Model of Aging". Another interesting one. Seems like a theoretical paper on the effect of accumulated mutations that don't affect us negatively until past reproductive age. Hypothesises that some of this could increase mutations in non-reproductive cells, leaving different random mutations around the body as we age.
The literature review section looks at a paper which lengthens telomeres in vitro by inserting a short circular bit of DNA matching the telomere repetition sequence's complement. The review has some concerns about validity and missing information to show that this did actually happen.
"Early Programming of Adult Longevity: Demographic and Experimental Studies". They look at 100,000 people that died in the 1990s in Kiev and see a "strong association" between the month of the year they were born in and longevity, with the lowest longevity for people born April to July, and highest around December. The July and December low/high agree with what the Gavrilovs found in their studies of aristocratic families (see http://readingrejuvenationresearch.blogspot.com/2011/02/season-of-birth-and-human-longevity.html ) . On a seemingly completely unrelated study, they look at the lifespan of fruit flies and see them living longer when they are irradiated with low doses of radiation. Their hypothesis is that both effects, and many other anti-aging treatments, are due to the hormetic effect (ie response to low level stressor). Would like to read this one.
"Neuroprotective, Anti-Apoptotic Effects of Apomorphine". Looks at apomorphine's effects on the brain, with the possible focus on Parkinson's.
"The Role of Somatic and Germline Mutations in Aging and a Mutation Interaction Model of Aging". Another interesting one. Seems like a theoretical paper on the effect of accumulated mutations that don't affect us negatively until past reproductive age. Hypothesises that some of this could increase mutations in non-reproductive cells, leaving different random mutations around the body as we age.
The literature review section looks at a paper which lengthens telomeres in vitro by inserting a short circular bit of DNA matching the telomere repetition sequence's complement. The review has some concerns about validity and missing information to show that this did actually happen.
Friday, January 20, 2012
December 2002, briefly
No content still. Almost nothing interesting either.
"Effect of DL-α-Lipoic Acid on the Status of Lipids and Membrane-Bound ATPases in Various Brain Regions of Aged Rats". Shoved lipoic acids into rats, levels of lipids in the brain went down. Had to double-check to make sure it wasn't the same paper as in the previous issue
"Comparison of a Broad Spectrum Anti-Aging Nutritional Supplement with and without the Addition of a DNA Repair Enhancing Cat's Claw Extract". They gave what sounds like a multi-vitamin with or without added cat claw extract to humans (?).
"A Comparison of Growth Hormone Administration and Exercise in the Elderly". Probably what it says. I could only read the introduction.
"The Third Annual Monte Carlo Anti-Aging Conference". This I wouldn't have minded reading.
A review of the book "Oxidative stress biomarkers and antioxidant protocols". Lab methods.
The literature review looking at a paper that gave amyloid beta peptides to embryonic mouse neurons and to some tumour line, and watched for effects on telomeres and telomerase.
"Effect of DL-α-Lipoic Acid on the Status of Lipids and Membrane-Bound ATPases in Various Brain Regions of Aged Rats". Shoved lipoic acids into rats, levels of lipids in the brain went down. Had to double-check to make sure it wasn't the same paper as in the previous issue
"Comparison of a Broad Spectrum Anti-Aging Nutritional Supplement with and without the Addition of a DNA Repair Enhancing Cat's Claw Extract". They gave what sounds like a multi-vitamin with or without added cat claw extract to humans (?).
"A Comparison of Growth Hormone Administration and Exercise in the Elderly". Probably what it says. I could only read the introduction.
"The Third Annual Monte Carlo Anti-Aging Conference". This I wouldn't have minded reading.
A review of the book "Oxidative stress biomarkers and antioxidant protocols". Lab methods.
The literature review looking at a paper that gave amyloid beta peptides to embryonic mouse neurons and to some tumour line, and watched for effects on telomeres and telomerase.
Thursday, January 19, 2012
September 2002 issue
Only abstracts. Another relatively thin issue, with only three papers, none of them very interesting.
"α-Lipoic Acid Enhances Reduced Glutathione, Ascorbic Acid, and α-Tocopherol in Aged Rats". Shoved lipoic acid into rats, levels of lipid peroxidation went down, and levels of vitamins C and E, and of reduced glutathione went up.
"Telomere Dynamics, Aging, and Cancer: Study of Human Syndromes Characteristic of Premature Aging". Looks at telomere length and endoreduplication (DNA replication outside cell replication) in Fanconi's anaemia, ataxia-telangiectasia, Bloom syndrome and xeroderma pigmentosum syndrome, all predisposing for cancer. Telomeres mostly shorter (not in xeroderma pigmentosum).
"Age-Related Susceptibility of Chemical Carcinogenesis in BALB/c Mice". They inject carcinogens into young, middle and old aged mice, count the number that get cancer (4/10, 10/10, and 1/10 respectively).
Literature review section again looks at an old paper, but one I hadn't heard of before, that analyses how much telomerase is active in young, middle and old aged rainbow trouts. Lots of telomerase activity everywhere at all ages, even compared to human tumour cells. Levels in muscle and brain cells down to human tumour cell levels. The title of the paper is 'Telomerase activity in "immortal" fish'. Do rainbow trouts not age? Couldn't find anything on a brief search.
"α-Lipoic Acid Enhances Reduced Glutathione, Ascorbic Acid, and α-Tocopherol in Aged Rats". Shoved lipoic acid into rats, levels of lipid peroxidation went down, and levels of vitamins C and E, and of reduced glutathione went up.
"Telomere Dynamics, Aging, and Cancer: Study of Human Syndromes Characteristic of Premature Aging". Looks at telomere length and endoreduplication (DNA replication outside cell replication) in Fanconi's anaemia, ataxia-telangiectasia, Bloom syndrome and xeroderma pigmentosum syndrome, all predisposing for cancer. Telomeres mostly shorter (not in xeroderma pigmentosum).
"Age-Related Susceptibility of Chemical Carcinogenesis in BALB/c Mice". They inject carcinogens into young, middle and old aged mice, count the number that get cancer (4/10, 10/10, and 1/10 respectively).
Literature review section again looks at an old paper, but one I hadn't heard of before, that analyses how much telomerase is active in young, middle and old aged rainbow trouts. Lots of telomerase activity everywhere at all ages, even compared to human tumour cells. Levels in muscle and brain cells down to human tumour cell levels. The title of the paper is 'Telomerase activity in "immortal" fish'. Do rainbow trouts not age? Couldn't find anything on a brief search.
Wednesday, January 18, 2012
June 2002 by the very few abstracts
Still without access and nothing here that would make them look hard for them elsewhere. Quite a light issue overall.
"Vitamin E and Age Alter Liver Mitochondrial Morphometry". Mice liver's mitochondria measured across different ages and vitamin E supplementation. Mitochondria smaller in vitamin E'd mice compared to controls in old mice. Also, as mice get older, their mitochondria elongate, also in vitamin E'd mice. I had no idea that mitochondria elongated with age.
"In Search of a Model Species for Aging Research: A Study of the Life Span of Tree Shrews". Using shrews for animal aging as a shortish-life (10-14 years) but evolutionary close animals (close compared to mice).
A review of de Grey's book "The mitochondrial free radical theory of aging".
The regular literature review column reviewing the original telomerase-gets-fibroblasts-to-replicate-and-not-look-senescent paper.
There was also a letter to the editor that I should read if I ever read Arking's paper on mortality plateau from last issue that looked interesting.
"Vitamin E and Age Alter Liver Mitochondrial Morphometry". Mice liver's mitochondria measured across different ages and vitamin E supplementation. Mitochondria smaller in vitamin E'd mice compared to controls in old mice. Also, as mice get older, their mitochondria elongate, also in vitamin E'd mice. I had no idea that mitochondria elongated with age.
"In Search of a Model Species for Aging Research: A Study of the Life Span of Tree Shrews". Using shrews for animal aging as a shortish-life (10-14 years) but evolutionary close animals (close compared to mice).
A review of de Grey's book "The mitochondrial free radical theory of aging".
The regular literature review column reviewing the original telomerase-gets-fibroblasts-to-replicate-and-not-look-senescent paper.
There was also a letter to the editor that I should read if I ever read Arking's paper on mortality plateau from last issue that looked interesting.
Tuesday, January 17, 2012
March 2002, by the abstracts
Still only reading the abstracts due to lack of access.
This issue is a continuation on the growth hormone papers from last issue. There is a lot more mentions of ghrelin in these papers than in the ones I read from 1999. It's one of the secretagogues.
"Relationship Between Exercise and Growth Hormone Neuroendocrine Function". A review of the effects of exercise on growth hormone. This one could be interesting.
"Cellular and Molecular Mechanisms of Growth Hormone Action on Skeletal Muscle: Implications for Treatment of Age-Associated Sarcopenia". How growth hormone/IGF-1 make muscles grow.
"Assessing Safety and Efficacy of Growth Hormone Replacement in Aging by Community Physicians". Review on safety profile I think.
"Growth Hormone: Challenges and Opportunities for the Biotechnology Sector". Some kind of review. Dunno.
"Localization and the Role of Growth Hormone Secretagogues in the Central Nervous System". Which bits of the brain the secretagogues touch.
"Growing Pains: Bioethical Perspectives on Growth Hormone Replacement Research". Ethics.
"Sex-Steroid Hormone Modulation of the Tripeptidyl Control of the Human Somatotropic Axis". I think it's on estrogen modulation of GH. Maybe testosterone too.
"N6-Furfuryladenine (Kinetin) as a Potential Anti-Aging Molecule". Something completely different. A cell-division inducer being touted as an anti-oxidant. Not growth hormone related, but doesn't sound like much fun either.
Book review of the 5th edition of the Handbook of the Biology of Aging. Supposedly good.
The usual literature review section reviewing a paper about alternative splicings of human telomerase reverse transcriptase, and possible control mechanisms of telomerase through control of splicing enzymes.
This issue is a continuation on the growth hormone papers from last issue. There is a lot more mentions of ghrelin in these papers than in the ones I read from 1999. It's one of the secretagogues.
"Relationship Between Exercise and Growth Hormone Neuroendocrine Function". A review of the effects of exercise on growth hormone. This one could be interesting.
"Cellular and Molecular Mechanisms of Growth Hormone Action on Skeletal Muscle: Implications for Treatment of Age-Associated Sarcopenia". How growth hormone/IGF-1 make muscles grow.
"Assessing Safety and Efficacy of Growth Hormone Replacement in Aging by Community Physicians". Review on safety profile I think.
"Growth Hormone: Challenges and Opportunities for the Biotechnology Sector". Some kind of review. Dunno.
"Localization and the Role of Growth Hormone Secretagogues in the Central Nervous System". Which bits of the brain the secretagogues touch.
"Growing Pains: Bioethical Perspectives on Growth Hormone Replacement Research". Ethics.
"Sex-Steroid Hormone Modulation of the Tripeptidyl Control of the Human Somatotropic Axis". I think it's on estrogen modulation of GH. Maybe testosterone too.
"N6-Furfuryladenine (Kinetin) as a Potential Anti-Aging Molecule". Something completely different. A cell-division inducer being touted as an anti-oxidant. Not growth hormone related, but doesn't sound like much fun either.
Book review of the 5th edition of the Handbook of the Biology of Aging. Supposedly good.
The usual literature review section reviewing a paper about alternative splicings of human telomerase reverse transcriptase, and possible control mechanisms of telomerase through control of splicing enzymes.
Monday, January 16, 2012
December 2001, sourceless.
Continuing the cheating. Only have abstracts available and I'm mostly happy about that, since it's an issue on growth hormone and I've had enough of that particular topic.
"Issues Regarding the Routine and Long-Term Use of Growth Hormone in Anti-Aging Medicine". Probably what it says in the title.
"A Word of Caution: Can Growth Hormone Accelerate Aging?". Creator of the GH receptor knock-out mice warning that growth hormone is maybe not great.
"Age-Related Decreases in Growth Hormone and Insulin-Like Growth Factor (IGF)–1: Implications for Brain Aging". Growth hormone and the brain, and why the knock-out mice are not relevant maybe.
"Growth Hormone Releasing Hormone Treatment in Normal Aging". 6 month study injecting growth hormone releasing hormone into old people. Lean body mass increase, abdominal fat decrease (5-8%), maybe improved cognition, no better sleep. Didn't work for women under estrogen supplementation.
"Natural and Synthetic Growth Hormone Secretagogues: Endocrine and Nonendocrine Activities Suggesting Their Potential Usefulness as Anti-Aging Drug Interventions". On the non-growth-hormonal effects of growth hormone secretagogues.
"Hormone Modulation, Low Glycemic Nutrition, and Exercise Instruction: Effects on Disease Risk and Quality of Life". Results of looking at 100 people on growth hormone, DHEA, testosterone, estrogen and progesterone supplementation.
"Growth Hormone Excess and Cancer". Does it make it more likely.
After that barrage, there is a short report on the second SENS roundtable, too short to have any details.
Finally, the usual literature review, looking at telomerase ectopically expressed in heart cells of mice. It inhibited apoptosis after heart attacks, and decreased affected area by 23%. Made the hearts bigger too.
"Issues Regarding the Routine and Long-Term Use of Growth Hormone in Anti-Aging Medicine". Probably what it says in the title.
"A Word of Caution: Can Growth Hormone Accelerate Aging?". Creator of the GH receptor knock-out mice warning that growth hormone is maybe not great.
"Age-Related Decreases in Growth Hormone and Insulin-Like Growth Factor (IGF)–1: Implications for Brain Aging". Growth hormone and the brain, and why the knock-out mice are not relevant maybe.
"Growth Hormone Releasing Hormone Treatment in Normal Aging". 6 month study injecting growth hormone releasing hormone into old people. Lean body mass increase, abdominal fat decrease (5-8%), maybe improved cognition, no better sleep. Didn't work for women under estrogen supplementation.
"Natural and Synthetic Growth Hormone Secretagogues: Endocrine and Nonendocrine Activities Suggesting Their Potential Usefulness as Anti-Aging Drug Interventions". On the non-growth-hormonal effects of growth hormone secretagogues.
"Hormone Modulation, Low Glycemic Nutrition, and Exercise Instruction: Effects on Disease Risk and Quality of Life". Results of looking at 100 people on growth hormone, DHEA, testosterone, estrogen and progesterone supplementation.
"Growth Hormone Excess and Cancer". Does it make it more likely.
After that barrage, there is a short report on the second SENS roundtable, too short to have any details.
Finally, the usual literature review, looking at telomerase ectopically expressed in heart cells of mice. It inhibited apoptosis after heart attacks, and decreased affected area by 23%. Made the hearts bigger too.
Sunday, January 15, 2012
September 2001 issue, by the abstracts
This issue seemed to be about calorie restriction. They all sound quite interesting. Only abstracts available.
"Mechanisms of Prolonged Longevity: Mutants, Knock-Outs, and Caloric Restriction". Compares growth hormone receptor knock-out mice with calorie-restricted mice.
"Caloric Restriction in Nonmammalian Models". A review of what is known about calorie restriction in non-mammals, and molecular commonalities among them.
"Endocrine Effects of Dietary Restriction and Aging: The National Institute on Aging Study". More data from the long-term rhesus study. This is a summary of hormonal changes, maybe focusing on melatonin and DHEA.
"Progress in the Development of Caloric Restriction Mimetic Dietary Supplements". Review of initial studies on caloric restriction mimetics. They mention 2-deoxy-D-glucose, phenformin and iodoacetate as examples.
A review of a book on telomeres and telomerase from a symposium in 1997.
The literature review section looked at a paper that inserted mutant versions of the RNA template component of telomerase into immortal lines, and watched them slow down growth.
"Mechanisms of Prolonged Longevity: Mutants, Knock-Outs, and Caloric Restriction". Compares growth hormone receptor knock-out mice with calorie-restricted mice.
"Caloric Restriction in Nonmammalian Models". A review of what is known about calorie restriction in non-mammals, and molecular commonalities among them.
"Endocrine Effects of Dietary Restriction and Aging: The National Institute on Aging Study". More data from the long-term rhesus study. This is a summary of hormonal changes, maybe focusing on melatonin and DHEA.
"Progress in the Development of Caloric Restriction Mimetic Dietary Supplements". Review of initial studies on caloric restriction mimetics. They mention 2-deoxy-D-glucose, phenformin and iodoacetate as examples.
A review of a book on telomeres and telomerase from a symposium in 1997.
The literature review section looked at a paper that inserted mutant versions of the RNA template component of telomerase into immortal lines, and watched them slow down growth.
Rest of June, 2001 issue by abstracts
Again, going just by abstracts:
"Antioxidant Genes, Hormesis, and Demographic Longevity" pushes a theoretical explanation for the mortality plateau at old age. Something to do with the Antioxidant Defense System ramping up. I always thought the effect was over-hyped and that it is not very important in humans. I wouldn't have minded reading it.
"The Impact of Glutathione on Health and Longevity". Lots about glutathione.
"The Role of L-Carnitine in the Activities of Membrane-Bound Enzymes in the Brains of Aged Rats". Lipid peroxidation leading to less activity for membrane enzymes in rats. L-carnitine lowering lipid peroxidation and raising membrane enzymes.
The regular literature review. They look at a paper on telomere length on cow clones. Telomere lengths look normal. Telomerase induced by the nuclear transfer process somehow.
"Antioxidant Genes, Hormesis, and Demographic Longevity" pushes a theoretical explanation for the mortality plateau at old age. Something to do with the Antioxidant Defense System ramping up. I always thought the effect was over-hyped and that it is not very important in humans. I wouldn't have minded reading it.
"The Impact of Glutathione on Health and Longevity". Lots about glutathione.
"The Role of L-Carnitine in the Activities of Membrane-Bound Enzymes in the Brains of Aged Rats". Lipid peroxidation leading to less activity for membrane enzymes in rats. L-carnitine lowering lipid peroxidation and raising membrane enzymes.
The regular literature review. They look at a paper on telomere length on cow clones. Telomere lengths look normal. Telomerase induced by the nuclear transfer process somehow.
When Does Human Longevity Start?: Demarcation of the Boundaries for Human Longevity
Interestingness:5
By Natalia S. Gavrilova and Leonid A. Gavrilov. Journal of Anti-Aging Medicine. June 2001, 4(2): 115-124. doi:10.1089/10945450152466161.
More Gavrilovs. This one is another paper where they continue to extract results from the historical records of the european aristocracy from the 1600s onwards. In this one, they focus on the period 1800-1880s so as to have complete data for women (recent records are more complete) but also to make sure everyone in it is dead.
They analyse longevity of 5800 daughters that made it to adulthood (30 years) compared to longevity of their mothers and fathers (separately). They avoid sons due to frequent military deaths. They find almost no correlation if the mother died before 85 years of age, but strong correlation otherwise, with a line of best fit with a slope of 0.412±0.204. Similarly for the father, with no correlation if he died before 75 years of age, but a strong correlation with a slope of 0.236±0.078 otherwise. They don't show results with a combined mother plus father variable. The graphs are quite nice.
There's something somewhat dodgy about the method since they were looking for a piecewise linear regression, and they determined where to start the significant line by inspecting the graph visually. I don't know how much that detracts from the result.
Like they mention, this does "resolve" the contradictions found where some research says that the genetic component of longevity is small, while others show that people with very old age are bunched in families.
By Natalia S. Gavrilova and Leonid A. Gavrilov. Journal of Anti-Aging Medicine. June 2001, 4(2): 115-124. doi:10.1089/10945450152466161.
More Gavrilovs. This one is another paper where they continue to extract results from the historical records of the european aristocracy from the 1600s onwards. In this one, they focus on the period 1800-1880s so as to have complete data for women (recent records are more complete) but also to make sure everyone in it is dead.
They analyse longevity of 5800 daughters that made it to adulthood (30 years) compared to longevity of their mothers and fathers (separately). They avoid sons due to frequent military deaths. They find almost no correlation if the mother died before 85 years of age, but strong correlation otherwise, with a line of best fit with a slope of 0.412±0.204. Similarly for the father, with no correlation if he died before 75 years of age, but a strong correlation with a slope of 0.236±0.078 otherwise. They don't show results with a combined mother plus father variable. The graphs are quite nice.
There's something somewhat dodgy about the method since they were looking for a piecewise linear regression, and they determined where to start the significant line by inspecting the graph visually. I don't know how much that detracts from the result.
Like they mention, this does "resolve" the contradictions found where some research says that the genetic component of longevity is small, while others show that people with very old age are bunched in families.
Saturday, January 14, 2012
Extension of Life-Span with Superoxide Dismutase/Catalase Mimetics
Interestingness: 4
By Simon Melov, Joanne Ravenscroft, Sarwatt Malik, Matt S Gill, David W Walker, Peter E Clayton, Douglas C Wallace, Bernard Malfroy, Susan R Doctrow and Gordon J Lithgow, in Science 1 September 2000, Volume 289, Issue 5484 (pp 1567-1569 DOI: 10.1126/science.289.5484.1567 )
This is one of the papers that was being reviewed in the gerontology review of the Journal of Anti-Aging Medicine. This supposed superoxide dismutase and catalase mimetics (EUK-8 and EUK-134), extend the average lifespan of C Elegans by 44%. Maximum lifespan also seems to go up by about that much. Strangely to me, the effect is not dose dependent, which they explain it to be due it most likely being ingested, and because they stop eating when they are old, the effect is self-limitting or something like that, but I don't see how that explanation explains much. Nice strong effect anyway.
By Simon Melov, Joanne Ravenscroft, Sarwatt Malik, Matt S Gill, David W Walker, Peter E Clayton, Douglas C Wallace, Bernard Malfroy, Susan R Doctrow and Gordon J Lithgow, in Science 1 September 2000, Volume 289, Issue 5484 (pp 1567-1569 DOI: 10.1126/science.289.5484.1567 )
This is one of the papers that was being reviewed in the gerontology review of the Journal of Anti-Aging Medicine. This supposed superoxide dismutase and catalase mimetics (EUK-8 and EUK-134), extend the average lifespan of C Elegans by 44%. Maximum lifespan also seems to go up by about that much. Strangely to me, the effect is not dose dependent, which they explain it to be due it most likely being ingested, and because they stop eating when they are old, the effect is self-limitting or something like that, but I don't see how that explanation explains much. Nice strong effect anyway.
Epidemiology of Human Longevity: The Search for Appropriate Methodology
Interestingness: 1
By Leonid A Gavrilov and Natalia S Gavrilova, in the Journal of Anti-Aging Medicine, March 2001 (pp 13-30, doi:10.1089/109454501750225659.)
So I found the paper anyway, on the Gavrilovs site, and I always read the Gavrilovs. This one wasn't interesting though. It's a longish paper suggesting a study to pick up genes that are associated with longevity, by looking at past records and looking at consanguinity and the age of the father at conception. They go through basis for the study, lost of things to look for and account for.
By Leonid A Gavrilov and Natalia S Gavrilova, in the Journal of Anti-Aging Medicine, March 2001 (pp 13-30, doi:10.1089/109454501750225659.)
So I found the paper anyway, on the Gavrilovs site, and I always read the Gavrilovs. This one wasn't interesting though. It's a longish paper suggesting a study to pick up genes that are associated with longevity, by looking at past records and looking at consanguinity and the age of the father at conception. They go through basis for the study, lost of things to look for and account for.
Friday, January 13, 2012
Out of material
My access to the journal has been cut, so I won't be able to keep doing this.
For now, I'll summarise what I am able to see in the abstracts, for future reference so that I can go back and see which ones sounded interesting.
Finishing issue 4 of 2000, there was the regular review of the gerontological literature column, but I'm only able to tell that one of the reviews was about AIDS shortening telomeres of CD4+ lymphocytes by inducing continuous replenishment.
On the first issue of 2001, there was:
Some meta-methodological paper by the Gavrilovs which I didn't grok from the abstract.
The Pierpaoli dude with his "crazy" experiments, implanting pineal glands from old and young rats into other young rats, and observing that those implanted old pineal glands aged and died younger but those with young pineal glands were not affected.
Another article characterising senescence-accelerated mice.
One of those very specific papers looking at effects of a variety of antioxidants on the oxidation of a variety of neurotransmitters.
Some experiments oxidising red blood cells with and without membranes, and something about the membranes making it worse due to lipid peroxidation, and quercetin (some flavonoid wikipedia tells me) helping somehow.
None of the papers sound very interesting, but I would read the pineal gland transplants one for fun.
Then there was a review of a book "Endocrinology of Aging", and the literature review which reviews at least one paper saying that inserting telomerase on CD8+ T cells doesn't immortalise them, and an extension of lifespan by superoxide dismutase/catalase mimetics, which I would be interested to read.
For now, I'll summarise what I am able to see in the abstracts, for future reference so that I can go back and see which ones sounded interesting.
Finishing issue 4 of 2000, there was the regular review of the gerontological literature column, but I'm only able to tell that one of the reviews was about AIDS shortening telomeres of CD4+ lymphocytes by inducing continuous replenishment.
On the first issue of 2001, there was:
Some meta-methodological paper by the Gavrilovs which I didn't grok from the abstract.
The Pierpaoli dude with his "crazy" experiments, implanting pineal glands from old and young rats into other young rats, and observing that those implanted old pineal glands aged and died younger but those with young pineal glands were not affected.
Another article characterising senescence-accelerated mice.
One of those very specific papers looking at effects of a variety of antioxidants on the oxidation of a variety of neurotransmitters.
Some experiments oxidising red blood cells with and without membranes, and something about the membranes making it worse due to lipid peroxidation, and quercetin (some flavonoid wikipedia tells me) helping somehow.
None of the papers sound very interesting, but I would read the pineal gland transplants one for fun.
Then there was a review of a book "Endocrinology of Aging", and the literature review which reviews at least one paper saying that inserting telomerase on CD8+ T cells doesn't immortalise them, and an extension of lifespan by superoxide dismutase/catalase mimetics, which I would be interested to read.
Wednesday, January 11, 2012
Age-Associated Plasma Lipids, Lipid Peroxidation, and Antioxidant Systems in Relation to Vitamin C Supplementation in Humans
Interestingness: 2
By Muthuvel Jayachandran, Palaniyappan Arivazhagan and Chinnakkannu Panneerselvam, in the Journal of Anti-Aging Medicine, Volume 3, Issue 4, 2000 (pp 437-445, doi:10.1089/rej.1.2000.3.437.)
They looked at vitamin C, cholesterol, lipid peroxides, and a whole bunch of antioxidants (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase) in young (20-30 year olds) and old (> 60 year olds) and see that antioxidants in old are lower, cholesterol and lipids are higher in old people. They give both groups 200 mg/day of vitamin C for 90 days. All numbers in old people get a lot better.
I'd have been more interested if I didn't already "know" that vitamin C does nothing good for mortality.
By Muthuvel Jayachandran, Palaniyappan Arivazhagan and Chinnakkannu Panneerselvam, in the Journal of Anti-Aging Medicine, Volume 3, Issue 4, 2000 (pp 437-445, doi:10.1089/rej.1.2000.3.437.)
They looked at vitamin C, cholesterol, lipid peroxides, and a whole bunch of antioxidants (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase) in young (20-30 year olds) and old (> 60 year olds) and see that antioxidants in old are lower, cholesterol and lipids are higher in old people. They give both groups 200 mg/day of vitamin C for 90 days. All numbers in old people get a lot better.
I'd have been more interested if I didn't already "know" that vitamin C does nothing good for mortality.
Monday, January 9, 2012
Adrenocortical Cells Immortalized by Telomerase: Potential Use for Ex Vivo Gene Therapy
Interestingness:2
By Peter J Hornsby, Khan Ozol, and Keyi Yang, in the Journal of Anti-Aging Medicine, Volume 3, Issue 4 2000 (pp 411-417, doi:10.1089/rej.1.2000.3.411.)
Report on injecting bovine adrenocortical cells into rat brains, after immortalisation via telomerisation and addition of SV40 T antigen, which suppresses p53 and retinoblastoma activation. In one experiment, they also added nerve growth factor (NGF) gene to see if it'd produce it.
Results: lots of immune reaction to the foreign tissue, even when using cyclosporin A, an immunosuppressant, so most cells killed quite quickly.
Also, brief review stating that telomerised cells don't induce tumours in nude mice, and look as if they maintain their cell type.
By Peter J Hornsby, Khan Ozol, and Keyi Yang, in the Journal of Anti-Aging Medicine, Volume 3, Issue 4 2000 (pp 411-417, doi:10.1089/rej.1.2000.3.411.)
Report on injecting bovine adrenocortical cells into rat brains, after immortalisation via telomerisation and addition of SV40 T antigen, which suppresses p53 and retinoblastoma activation. In one experiment, they also added nerve growth factor (NGF) gene to see if it'd produce it.
Results: lots of immune reaction to the foreign tissue, even when using cyclosporin A, an immunosuppressant, so most cells killed quite quickly.
Also, brief review stating that telomerised cells don't induce tumours in nude mice, and look as if they maintain their cell type.
Thursday, January 5, 2012
Telomere Length Dynamics in Normal and Malignant Hematopoiesis
Interestingness: 2
By Tim H Brümmendorf, Peter M Lansdorp and Nathalie Rufer, in the Journal of Anti-Aging Medicine, Volume 3, Issue 4, 2000 (pp 397-409, doi:10.1089/rej.1.2000.3.397.)
This seems to be a double-length episode of the previous paper, relating how telomere lengths change in blood cells across time and diseases. One thing it clarified was that they thought the shortening of telomeres in bone marrow donor recipients was due to the repopulation of the bone marrow stem cells from the few donor cells. Also, they kept on a theme that the telomere lengths of most blood cells are merely reflecting the lengths in the haematopoietic stem cells (HSC aka bone marrow stem cells) which produced them.
By Tim H Brümmendorf, Peter M Lansdorp and Nathalie Rufer, in the Journal of Anti-Aging Medicine, Volume 3, Issue 4, 2000 (pp 397-409, doi:10.1089/rej.1.2000.3.397.)
This seems to be a double-length episode of the previous paper, relating how telomere lengths change in blood cells across time and diseases. One thing it clarified was that they thought the shortening of telomeres in bone marrow donor recipients was due to the repopulation of the bone marrow stem cells from the few donor cells. Also, they kept on a theme that the telomere lengths of most blood cells are merely reflecting the lengths in the haematopoietic stem cells (HSC aka bone marrow stem cells) which produced them.
Tuesday, January 3, 2012
Telomerase Activity and Telomere Length in the Haemopoietic System: Changes with Aging, Disease, and Therapy
Interestingness: 3
By JD Robertson and RF Wynn, in the Journal of Anti-Aging Medicine, Volume 3, Issue 4, 2000 (pp 389-395, doi:10.1089/rej.1.2000.3.389)
Review of what was known about telomere length and telomerase in blood cells. Haemopoietic stem cells (HSC) have active telomerase but their telomeres shorten gradually. Same for T-cells. Telomeres in neutrophils also shorten at about the same rate as in T-cells (20-50 base pairs per year), but from what I understood, they don't have active telomerase, so the telomerase is acting as a compensation method for the occasional clonal expansion of T-cells.
Checking for which X chromosome is inactivated, in old women most blood cells have the same one, as if they come from fewer and fewer stem cells.
In people with acute leukemia, telomeres are short and telomerase long, and they suggest this suggests that telomerase activates late in the process of disease. Also short telomeres on aplastic anemia and Fanconi's anemia. Also shorter telomeres in bone marrow transplant recipients than in donors (about 15 years worth), but I'm not clear if they are saying this is because the transplanted tissue has had to undergo quick replication to refill the recipient's system, or that this was there before.
By JD Robertson and RF Wynn, in the Journal of Anti-Aging Medicine, Volume 3, Issue 4, 2000 (pp 389-395, doi:10.1089/rej.1.2000.3.389)
Review of what was known about telomere length and telomerase in blood cells. Haemopoietic stem cells (HSC) have active telomerase but their telomeres shorten gradually. Same for T-cells. Telomeres in neutrophils also shorten at about the same rate as in T-cells (20-50 base pairs per year), but from what I understood, they don't have active telomerase, so the telomerase is acting as a compensation method for the occasional clonal expansion of T-cells.
Checking for which X chromosome is inactivated, in old women most blood cells have the same one, as if they come from fewer and fewer stem cells.
In people with acute leukemia, telomeres are short and telomerase long, and they suggest this suggests that telomerase activates late in the process of disease. Also short telomeres on aplastic anemia and Fanconi's anemia. Also shorter telomeres in bone marrow transplant recipients than in donors (about 15 years worth), but I'm not clear if they are saying this is because the transplanted tissue has had to undergo quick replication to refill the recipient's system, or that this was there before.
Monday, January 2, 2012
DNA Damage and Telomere Length in Human T Cells
Interestingness: 3
By Yvonne A Barnett, Christopher R Barnett, and Thomas Von Zglinicki, in the Journal of Anti-Aging Medicine, Volume 3, Issue 4, 2000 (pp 383-388, doi:10.1089/rej.1.2000.3.383. )
Seemed speculative on the link between T-cell, telomere length and oxidation damage in vivo, but presented a series of facts to suggest a link: increasing mutations in one particular gene in lymphocytes with age, senescent-looking T-cells in vivo in centenarians and people with Down's syndrome, and fibroblast with higher anti-oxidant capacity having a slower telomere shortening rate in vitro.
(Interesting: link between shorter telomeres and vascular dementia, but not with Alzheimer's, stroke or heart attack)
By Yvonne A Barnett, Christopher R Barnett, and Thomas Von Zglinicki, in the Journal of Anti-Aging Medicine, Volume 3, Issue 4, 2000 (pp 383-388, doi:10.1089/rej.1.2000.3.383. )
Seemed speculative on the link between T-cell, telomere length and oxidation damage in vivo, but presented a series of facts to suggest a link: increasing mutations in one particular gene in lymphocytes with age, senescent-looking T-cells in vivo in centenarians and people with Down's syndrome, and fibroblast with higher anti-oxidant capacity having a slower telomere shortening rate in vitro.
(Interesting: link between shorter telomeres and vascular dementia, but not with Alzheimer's, stroke or heart attack)
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