By the abstracts:
"Selective Mitochondrial Autophagy, or Mitophagy, as a Targeted Defense Against Oxidative Stress, Mitochondrial Dysfunction, and Aging". Piece reviewing the autophagy of mitochondria, and that it seems to be targeted, and maybe important. Has over 100 citations. Might have to find it.
"Mitochondrial DNA Gene Therapy: A Gene Therapy for Aging?". Talks about the possible importance of mtDNA problems and probably of the mtDNA to nDNA therapy paper in this issue.
"Novel Routes for Metabolism of 7-Ketocholesterol". About a possible new breakdown path for 7-ketocholesterol. 7-ketocholesterol is one of the substance in atherosclerotic plaques.
"Reactive Oxygen Species Production in the Mitochondrial Matrix: Implications for the Mechanism of Mitochondrial Mutation Accumulation". Theorising about implications of newly discovered ways in which mtDNA mutations can trigger increases in reactive oxygen species. Interesting.
"Stable Transformation of CHO Cells and Human NARP Cybrids Confers Oligomycin Resistance (olir) Following Transfer of a Mitochondrial DNA–Encoded olir ATPase6 Gene to the Nuclear Genome: A Model System for mtDNA Gene Therapy". They grabbed a gene that gave chinese hamster cells resistance to oligomycin (some antibiotic) that sat in their mtDNA, changed it so that it would work if inserted into nuclear DNA, and tested it by inserting it into normal chinese hamster cells and dipping them in oligomycin. de Grey thinks this is the most important paper yet published in Rejuvenation Research, so I'll have to read it.
"Thermodynamics and Information in Aging: Why Aging Is Not a Mystery and How We Will Be Able to Make Rational Interventions". Theoretical paper deriving aging from thermodynamics. Sometimes I like these papers, sometimes they are terrible. I'll have to have a glance.
"Genetically Modified Hairy Roots of Withania somnifera Dunal: A Potent Source of Rejuvenating Principles". I don't have much idea of what this one is about. I found the abstract very confusing. Something about enhancing the antioxidant effects of Withania somnifera, maybe.
"Gerontomodulatory and Youth-Preserving Effects of Zeatin on Human Skin Fibroblasts Undergoing Aging In Vitro". Another one which I didn't understand very well. Something about zeatin, a plant growth factor, keeping fibroblasts young-looking, but without increasing proliferative capacity.
Thursday, January 31, 2013
Monday, September 3, 2012
Issue 4, 2004
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.
"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.
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
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