By the abstracts:
"Targeting Telomerase". Review of techniques and issues regarding hammering telomerase as an anti-cancer treatment, and whether that would select for ALT-cancers (ALT constitute 10-15% of cancers atm). Of note, the existence of a TERT vaccine.
"Telomere and TRF2/MTBP Localization in Respect to Satellite DNA During the Cell Cycle of Mouse Cell Line L929" About what happens to telomeres as the cells goes through its cycle in mice. Mostly goes over my head.
"Werner Syndrome as an Example of Inflamm-aging: Possible Therapeutic Opportunities for a Progeroid Syndrome?" Title is a good summary of the abstract.
"Stimulation of Macroautophagy Can Rescue Older Cells from 8-OHdG mtDNA Accumulation: A Safe and Easy Way to Meet Goals in the SENS Agenda" They stimulate macroautophagy by injecting agents that stop the breakdown of triglycerides in rat liver cells. This gets rid of 8-OHdG accumulation in the mtDNA in six hours.
Also, a report on SENS 2 by Aubrey de Grey that I'd like to read.
Overall, I don't mind as much not having access to the articles in this issue.
Monday, February 10, 2014
Cryopreservation of Complex Systems: The Missing Link in the Regenerative Medicine Supply Chain
Interestingness: 6
By Gregory M. Fahy, Brian Wowk, and Jun Wu. Rejuvenation Research. Summer 2006, 9(2): 279-291. doi:10.1089/rej.2006.9.279.
They pump the idea of using cryogenics to store pre-produced organs for use in transplants. They start with some interesting numbers regarding yearly US deaths that could be prevented if there were available organs:
in total forming 36.2% of all yearly US deaths. They seem to be assigning all heart disease deaths as solvable by a heart transplant, etc. They also have a corresponding graph showing survival curves (ie age vs percentage alive) for status quo vs with those transplants, assuming no deaths during the transplants, with the transplant curve really diverging after 70 years of age with the transplant survival to status quo survival ratio of two at 80 and of 18 at 90. I don't know why they chose to show numbers that are so clearly not conservative.
They see cryopreservation as a necessary tool to manage the supply chain of organs manufactured through regenerative medicine to make mass organ availability viable. This is seen by them as the interim solution until in-situ recreation of the organ becomes a possibility.
They then describe a brief history of the cryopreservation of organs by straight freezing:
They claim straight-freezing of vital organs won't work because the vascular system is too easily damaged by freezing. This leads to methods that try to avoid freezing damage by avoiding ice formation.
In 1965, red blood cells and guinea pig uteri were lowered to -79C by lowering the freezing point of water and keeping it liquid all the way to the target temperature. Then in the 1980s, vitrification experiments started where the material is cooled into a glass without forming ice, starting with the vitrification of mouse embryos in 1985.
Experiments with vitrifications suggest that toxicity of cryoprotectant is due to reduced water availability for biomolecules. "Winner" of the cryoprotectants is M22 which seems to be used only below -22C with some other cryoprotectant (VMP) used to go from room temperature to -22C. Not much idea of what M22 consists of but it has a carrier solution that is meant to lower the toxicity combined with many anti-nucleating substances.
When ten rabbit kidneys were cooled to -22C, M22ised, deM22ised and rewarmed, then transplanted into rabbits, all rabbits survived (the non-cooled kidney is extracted in the experiments to make sure that the rabbits depend on the transplanted kidney), but there is more injury to the M22-ised kidneys than what is seen when just cooling them to -3C with VMP. Eight rabbit kidneys taken to -50C using M22 seem fine once rewarmed/deM22ised. Extra injury in M22-ised kidneys might be due to extra handling or extra time at cold temperature.
Newest experiment (2005) does the same rabbit kidney vitrification and transplantation on one rabbit with the rabbit surviving for 48 days after transplantation before it is killed. The cryoprotected kidney is cooled to below the glass transition temperature for M22 (-123C). Lots of damage to the kidney on this one, with hints that more even perfusion is needed.
By Gregory M. Fahy, Brian Wowk, and Jun Wu. Rejuvenation Research. Summer 2006, 9(2): 279-291. doi:10.1089/rej.2006.9.279.
They pump the idea of using cryogenics to store pre-produced organs for use in transplants. They start with some interesting numbers regarding yearly US deaths that could be prevented if there were available organs:
- Heart 710,760
- Lung 122,009
- Kidney 37,251
- Liver 16,214
in total forming 36.2% of all yearly US deaths. They seem to be assigning all heart disease deaths as solvable by a heart transplant, etc. They also have a corresponding graph showing survival curves (ie age vs percentage alive) for status quo vs with those transplants, assuming no deaths during the transplants, with the transplant curve really diverging after 70 years of age with the transplant survival to status quo survival ratio of two at 80 and of 18 at 90. I don't know why they chose to show numbers that are so clearly not conservative.
They see cryopreservation as a necessary tool to manage the supply chain of organs manufactured through regenerative medicine to make mass organ availability viable. This is seen by them as the interim solution until in-situ recreation of the organ becomes a possibility.
They then describe a brief history of the cryopreservation of organs by straight freezing:
- 1950s - Freezing of guinea pig uteri to dry ice temperature (< -79C) and back. Contractile responses in vitro.
- 1973 - Freezing of dog intestines to liquid nitrogen temperature (< -196C). Long term survival of small parts of it.
- 2002 - Freezing of rat ovaries. Survival of some and offspring in one after transplantation back into rats. They say this is not a good test since the ovaries can regenerate even if completely screwed up.
- 2003 - Freezing of sheep ovaries. Vascular patency (unobstructed) retained in 3 of 11 grafts and follicle-stimulating hromone levels kept to normal limits. Second report claiming higher patency rates using directional freezing.
They claim straight-freezing of vital organs won't work because the vascular system is too easily damaged by freezing. This leads to methods that try to avoid freezing damage by avoiding ice formation.
In 1965, red blood cells and guinea pig uteri were lowered to -79C by lowering the freezing point of water and keeping it liquid all the way to the target temperature. Then in the 1980s, vitrification experiments started where the material is cooled into a glass without forming ice, starting with the vitrification of mouse embryos in 1985.
Experiments with vitrifications suggest that toxicity of cryoprotectant is due to reduced water availability for biomolecules. "Winner" of the cryoprotectants is M22 which seems to be used only below -22C with some other cryoprotectant (VMP) used to go from room temperature to -22C. Not much idea of what M22 consists of but it has a carrier solution that is meant to lower the toxicity combined with many anti-nucleating substances.
When ten rabbit kidneys were cooled to -22C, M22ised, deM22ised and rewarmed, then transplanted into rabbits, all rabbits survived (the non-cooled kidney is extracted in the experiments to make sure that the rabbits depend on the transplanted kidney), but there is more injury to the M22-ised kidneys than what is seen when just cooling them to -3C with VMP. Eight rabbit kidneys taken to -50C using M22 seem fine once rewarmed/deM22ised. Extra injury in M22-ised kidneys might be due to extra handling or extra time at cold temperature.
Newest experiment (2005) does the same rabbit kidney vitrification and transplantation on one rabbit with the rabbit surviving for 48 days after transplantation before it is killed. The cryoprotected kidney is cooled to below the glass transition temperature for M22 (-123C). Lots of damage to the kidney on this one, with hints that more even perfusion is needed.
Monday, February 3, 2014
Issue 2, 2006
This issue is the second part of the papers presented in SENS 2005. By the abstracts:
Section 5: Mitochondria and Oxidative Damage
"Extracellular Redox State: Refining the Definition of Oxidative Stress in Aging" suggests that blood glutathione/glutathione disulfide ratio does not equilibrate with blood cysteine/cystine ratio, that the latter is not just a diagnostic but that it affects cell proliferation and oxidant-induced apoptosis, and that both ratios are good controlling indicators of oxidative stress. Or something like that, I haven't done this for a while and seem to have lost the knack. Lots of citations for this one.
"Factors That Might Affect the Allotopic Replacement of a Damaged Mitochondrial DNA-Encoded Protein". Review of successful allotopic expression of mitochondrial genes ported to the nuclear DNA and possible issues with getting those proteins into the inner membrane of the mitochondria. Sounds interesting.
"Can a Single Subunit Yeast NADH Dehydrogenase (Ndi1) Remedy Diseases Caused by Respiratory Complex I Defects?" They introduced NDi1, which transfers electrons from NADH to ubiquinone in yeast, into mammalian cells, some missing Complex 1. NDi1 inserted itself into the inner membrane of mitochondria and rescued the cells that were lacking Complex 1. They got it working on mice muscles and brains. Interesting.
"Protective Efficacy of α-Lipoic Acid on Acetylcholinesterase Activity in Aged Rat Brain Regions". Pumped alpha-lipoic acid into old rats, saw acetylcholinesterase levels restored in some parts of their brain.
"Cytochemical Estimation of Cytochrome Oxidase Activity as a Morphofunctional Mitochondrial Check-Up". They propose that measuring the ratio of cytochemical precipitate to mitochondrial area would give a good indication of mitochondrial function since the ratio decreased by 25% with aging.
"From Disease-Oriented to Aging/Longevity-Oriented Studies". Not sure what this is. Abstract sounds like the general aging IS a disease drive, with a focus on epigenetics, but hard to tell. Quite a few citations.
"Tissue-Specific Effect of Age and Caloric Restriction Diet on Mitochondrial DNA Content". CR reversed the drop in mtDNA in old rat livers and leg muscles, and increased the mtDNA of the brain, even though there is no drop there in ad-libitum rats.
"Testing Mitochondrial Metabolic Competence by Cytochrome Oxidase Preferential Cytochemistry Versus Immunoreactivity of Subunits I and IV". COX activity dropped with age in rats but not levels of two of its subunits.
"Caloric Restriction Protects Mitochondrial Function with Aging in Skeletal and Cardiac Muscles" 25 to 46% drop in oxidative capacity markers for ad-libitum-fed 'animals' (who knows what animals). None for CR. A lot of citations.
"Mitochondrial Genome Anatomy and Species-Specific Lifespan" Maximum lifespan is correlated with amount of cytosine in the DNA of mammal species, especially for primates. Vaguely interesting.
"Relationship Between Aging and Susceptibility of Erythrocytes to Oxidative Damage: In View of Nutraceutical Interventions". Placebo-controlled study feeding fermented papaya preparation to old people. Rescued abnormal higher concentration of nitric oxide synthase and malondialdehyde (a marker for oxidative stress) in red blood cells of old people compared to young people.
"Aging-Related Cell Surface ECTO-NOX Protein, arNOX, a Preventive Target to Reduce Atherogenic Risk in the Elderly". Cell-surface electron-transport protein associated with aging that can produce superoxide and thus oxidise circulating lipoproteins.
Section 6: Molecular Crosslinking and Aggregation
"Emerging Strategies for the Treatment of Hereditary Metabolic Storage Disorders" looks at solutions other than enzyme replacement for Gaucher and Fabry disease, which are diseases caused by mutations to enzymes that break down the stuff left over when senescent cells die.
"Advanced Atherosclerotic Foam Cell Formation Has Features of an Acquired Lysosomal Storage Disorder". Reviews the evidence for the foam cells in atherosclerosis to be due to an acquired lysosomal storage disorder. That is, the lysosomes are failing to break down what is sent to them so the material acumulates in the cell. Quite a few citations for this one.
"Indirect Antioxidant Protection Against Photooxidative Processes Initiated in Retinal Pigment Epithelial Cells by a Lipofuscin Pigment". Claims lipofuscin A2E triggers oxidation damage in retinal epithelial cells and is protected from this by glutathione and sulforaphane.
"Prevention and Repair of Protein Damage by the Maillard Reaction In Vivo". Equivalence between Maillard recation and advanced glycation end products (AGEs). 20 AGEs in human skin. No evidence of AGE breakers of breaking crosslinks in vivo. Maybe interesting, at least to learn about AGEs.
"Extracellular Glycation Crosslinks: Prospects for Removal". Two proposed methods of getting rid of glucosepane and K2P crosslinks. One is upping extracellular matrix turnover. A second one is high-throughput screening for molecules that can break those two down.
Section 7: Miscellaneous
"Cryopreservation of Complex Systems: The Missing Link in the Regenerative Medicine Supply Chain". On the potential use of vitrification to store organs, created through regenerative medicine, for transplanting when necessary. Claims routine recovery of vitrified rabbit kidneys cooled to -45 degrees celsius functioning properly after rewarming and being transplanted back into rabbits. Found the article. Might write one for it.
"Cryptobiosis, Aging, and Cancer: Yin-Yang Balancing of Signaling Networks". Aging as unbalanced complex signaling pathways.
"The Neurosecretory System Is Hypertrophied in Senescence-Accelerated Mice". Analysis of the neurosecretory system of senescence-accelerated mice.
"Natural Background Radioactive Carbon and the Natural Death Rate of People". Correlation between levels of carbon-14 in the atmosphere and death rates over the last 150 years. Notable mainly because the author's organisation is given as 'independent researcher'. Didn't think that was possible in this century.
"Radiocarbon Mechanism of Aging". More on carbon-14 and death rates by independent researchers, offering a mechanism of aging by carbon-14.
"Variations of Humans' Natural Death Rate and the Radiocarbon Aging Mechanism". More carbon-14 and mortality.
"Statistical Issues of Regression Analysis on Development of an Age-Predictive Equation". Equations to predict age from physical fitness measurements training on 31 Japanese males.
"Soft Strategies for Postponing Aging and Prolonging Human Life". Postponing aging by looking at things that cause discomfort and stopping things from becoming major.
"Psychosocial Aspects and Zinc Status: Is There a Relationship with Successful Aging?". Low albumin, as indicator for zinc, correlated with higher levels of depression in old Italians.
"Liver Exposure to Xenobiotics: The Aging Factor and Potentials for Functional Foods". Study on liver cells from young and old rats cultured with and without alpha-linolenic acid and given YHK (a herbal supplement I'd never heard of) or sylibin. They then gave them copper and iron. YHK did better at some things.
"The Aging Gut Motility Decay: May Symbiotics Be Acting as "Implantable" Biologic Pace-Makers?" Symbiotic (I don't know what that is) SCM-III (also no idea) does something to old rats' colons and jejunum.
"How Evolutionary Thinking Affects People's Ideas About Aging Interventions". From a person that belong to the group that think that aging is an evolutionarily programmed response. Mentions apoptosis and senescence via telomere shortening as behaviours that seem to shorten lifespan. Also, NSAIDs slowing arthritis, cancer and atherosclerosis as evidence for inflammation as programmed autoimmune response.
"Zinc Homeostasis in Aging: Two Elusive Faces of the Same 'Metal'". Aging creates zinc dyshomeostasis, not zinc deficiency.
"Aging and Oral Health Related to Quality of Life in Geriatric Patients". Survey of 53 70-year old Bulgarians regarding reasons they go to the dentist. 32% for acute pain and the rest for caries.
"Is Thrombolytic Therapy Effective in Elderly Patients?". Clinical (single-arm?) study doing thrombolytic therapy on 103 heart attacked people over 75. They say it had a positive effect.
"Negligible Senescence: How Will We Know It When We See It?". Suggests the use of global index of aging rate as units of functional change per time.
Section 5: Mitochondria and Oxidative Damage
"Extracellular Redox State: Refining the Definition of Oxidative Stress in Aging" suggests that blood glutathione/glutathione disulfide ratio does not equilibrate with blood cysteine/cystine ratio, that the latter is not just a diagnostic but that it affects cell proliferation and oxidant-induced apoptosis, and that both ratios are good controlling indicators of oxidative stress. Or something like that, I haven't done this for a while and seem to have lost the knack. Lots of citations for this one.
"Factors That Might Affect the Allotopic Replacement of a Damaged Mitochondrial DNA-Encoded Protein". Review of successful allotopic expression of mitochondrial genes ported to the nuclear DNA and possible issues with getting those proteins into the inner membrane of the mitochondria. Sounds interesting.
"Can a Single Subunit Yeast NADH Dehydrogenase (Ndi1) Remedy Diseases Caused by Respiratory Complex I Defects?" They introduced NDi1, which transfers electrons from NADH to ubiquinone in yeast, into mammalian cells, some missing Complex 1. NDi1 inserted itself into the inner membrane of mitochondria and rescued the cells that were lacking Complex 1. They got it working on mice muscles and brains. Interesting.
"Protective Efficacy of α-Lipoic Acid on Acetylcholinesterase Activity in Aged Rat Brain Regions". Pumped alpha-lipoic acid into old rats, saw acetylcholinesterase levels restored in some parts of their brain.
"Cytochemical Estimation of Cytochrome Oxidase Activity as a Morphofunctional Mitochondrial Check-Up". They propose that measuring the ratio of cytochemical precipitate to mitochondrial area would give a good indication of mitochondrial function since the ratio decreased by 25% with aging.
"From Disease-Oriented to Aging/Longevity-Oriented Studies". Not sure what this is. Abstract sounds like the general aging IS a disease drive, with a focus on epigenetics, but hard to tell. Quite a few citations.
"Tissue-Specific Effect of Age and Caloric Restriction Diet on Mitochondrial DNA Content". CR reversed the drop in mtDNA in old rat livers and leg muscles, and increased the mtDNA of the brain, even though there is no drop there in ad-libitum rats.
"Testing Mitochondrial Metabolic Competence by Cytochrome Oxidase Preferential Cytochemistry Versus Immunoreactivity of Subunits I and IV". COX activity dropped with age in rats but not levels of two of its subunits.
"Caloric Restriction Protects Mitochondrial Function with Aging in Skeletal and Cardiac Muscles" 25 to 46% drop in oxidative capacity markers for ad-libitum-fed 'animals' (who knows what animals). None for CR. A lot of citations.
"Mitochondrial Genome Anatomy and Species-Specific Lifespan" Maximum lifespan is correlated with amount of cytosine in the DNA of mammal species, especially for primates. Vaguely interesting.
"Relationship Between Aging and Susceptibility of Erythrocytes to Oxidative Damage: In View of Nutraceutical Interventions". Placebo-controlled study feeding fermented papaya preparation to old people. Rescued abnormal higher concentration of nitric oxide synthase and malondialdehyde (a marker for oxidative stress) in red blood cells of old people compared to young people.
"Aging-Related Cell Surface ECTO-NOX Protein, arNOX, a Preventive Target to Reduce Atherogenic Risk in the Elderly". Cell-surface electron-transport protein associated with aging that can produce superoxide and thus oxidise circulating lipoproteins.
Section 6: Molecular Crosslinking and Aggregation
"Emerging Strategies for the Treatment of Hereditary Metabolic Storage Disorders" looks at solutions other than enzyme replacement for Gaucher and Fabry disease, which are diseases caused by mutations to enzymes that break down the stuff left over when senescent cells die.
"Advanced Atherosclerotic Foam Cell Formation Has Features of an Acquired Lysosomal Storage Disorder". Reviews the evidence for the foam cells in atherosclerosis to be due to an acquired lysosomal storage disorder. That is, the lysosomes are failing to break down what is sent to them so the material acumulates in the cell. Quite a few citations for this one.
"Indirect Antioxidant Protection Against Photooxidative Processes Initiated in Retinal Pigment Epithelial Cells by a Lipofuscin Pigment". Claims lipofuscin A2E triggers oxidation damage in retinal epithelial cells and is protected from this by glutathione and sulforaphane.
"Prevention and Repair of Protein Damage by the Maillard Reaction In Vivo". Equivalence between Maillard recation and advanced glycation end products (AGEs). 20 AGEs in human skin. No evidence of AGE breakers of breaking crosslinks in vivo. Maybe interesting, at least to learn about AGEs.
"Extracellular Glycation Crosslinks: Prospects for Removal". Two proposed methods of getting rid of glucosepane and K2P crosslinks. One is upping extracellular matrix turnover. A second one is high-throughput screening for molecules that can break those two down.
Section 7: Miscellaneous
"Cryopreservation of Complex Systems: The Missing Link in the Regenerative Medicine Supply Chain". On the potential use of vitrification to store organs, created through regenerative medicine, for transplanting when necessary. Claims routine recovery of vitrified rabbit kidneys cooled to -45 degrees celsius functioning properly after rewarming and being transplanted back into rabbits. Found the article. Might write one for it.
"Cryptobiosis, Aging, and Cancer: Yin-Yang Balancing of Signaling Networks". Aging as unbalanced complex signaling pathways.
"The Neurosecretory System Is Hypertrophied in Senescence-Accelerated Mice". Analysis of the neurosecretory system of senescence-accelerated mice.
"Natural Background Radioactive Carbon and the Natural Death Rate of People". Correlation between levels of carbon-14 in the atmosphere and death rates over the last 150 years. Notable mainly because the author's organisation is given as 'independent researcher'. Didn't think that was possible in this century.
"Radiocarbon Mechanism of Aging". More on carbon-14 and death rates by independent researchers, offering a mechanism of aging by carbon-14.
"Variations of Humans' Natural Death Rate and the Radiocarbon Aging Mechanism". More carbon-14 and mortality.
"Statistical Issues of Regression Analysis on Development of an Age-Predictive Equation". Equations to predict age from physical fitness measurements training on 31 Japanese males.
"Soft Strategies for Postponing Aging and Prolonging Human Life". Postponing aging by looking at things that cause discomfort and stopping things from becoming major.
"Psychosocial Aspects and Zinc Status: Is There a Relationship with Successful Aging?". Low albumin, as indicator for zinc, correlated with higher levels of depression in old Italians.
"Liver Exposure to Xenobiotics: The Aging Factor and Potentials for Functional Foods". Study on liver cells from young and old rats cultured with and without alpha-linolenic acid and given YHK (a herbal supplement I'd never heard of) or sylibin. They then gave them copper and iron. YHK did better at some things.
"The Aging Gut Motility Decay: May Symbiotics Be Acting as "Implantable" Biologic Pace-Makers?" Symbiotic (I don't know what that is) SCM-III (also no idea) does something to old rats' colons and jejunum.
"How Evolutionary Thinking Affects People's Ideas About Aging Interventions". From a person that belong to the group that think that aging is an evolutionarily programmed response. Mentions apoptosis and senescence via telomere shortening as behaviours that seem to shorten lifespan. Also, NSAIDs slowing arthritis, cancer and atherosclerosis as evidence for inflammation as programmed autoimmune response.
"Zinc Homeostasis in Aging: Two Elusive Faces of the Same 'Metal'". Aging creates zinc dyshomeostasis, not zinc deficiency.
"Aging and Oral Health Related to Quality of Life in Geriatric Patients". Survey of 53 70-year old Bulgarians regarding reasons they go to the dentist. 32% for acute pain and the rest for caries.
"Is Thrombolytic Therapy Effective in Elderly Patients?". Clinical (single-arm?) study doing thrombolytic therapy on 103 heart attacked people over 75. They say it had a positive effect.
"Negligible Senescence: How Will We Know It When We See It?". Suggests the use of global index of aging rate as units of functional change per time.
Monday, April 1, 2013
Issue 1, 2006
This issue and the next are all about the SENS 2005 meeting. I'm still going by the abstracts though, since that's the best I've got.
Section 1: Stem Cells and Regeneration
"Conjecture: Can Continuous Regeneration Lead to Immortality? Studies in the MRL Mouse". Separate summary since I found the article and it sounded interesting
"Sustained Stromal Stem Cell Self-Renewal and Osteoblastic Differentiation During Aging". Characterisation of a line of stem cells isolated in bone marrow that can differentiate into all (?) other types. Frequency decreases from 0.01% of bone marrow cells when 3 years old to 0.0018% at 45 but doesn't go down after that. Interesting but probably too basic-sciency to incorporate.
"To Make a New Intestinal Mucosa". Grabbed some rats, chopped a quarter of their small intestine, making them leak bile in their shit, grabbed intestinal stem cells from newborn rats, and combined them with a separate bit of cleaned up section of intestine (from different rats I assume), and inserted the reformed bit at the end of their small intestines. Worked (as in no more bile leakage). They also did some other experiment with plastic scaffolds and being able to look at the implanted cells in vivo. It all sounds interesting.
"Transfection of CCE Mouse Embryonic Stem Cells with EGFP and BDNF Genes by the Electroporation Method". They show they can insert genes into stem cells by electroporation of plasmids and have them expressed.
"Glucose-Induced Replicative Senescence in Mesenchymal Stem Cells". Calorie restriction experiment in-vitro in which the mesenchymal stem cells which get less sugar die less and have higher replicative potential.
Section 2: Cancer, Cell Senescence, and Telomeres
"Gene Therapy That Safely Targets and Kills Tumor Cells Throughout the Body". Separate summary.
"Catechin-Vanilloid Synergies with Potential Clinical Applications in Cancer". Combination of two molecules inhibit expression of tNOX which is a molecule supposedly expressed only in cancers, and supposedly necessary for cancer growth.
"Multilocus Genotypes Spanning Estrogen Metabolism Associated with Breast Cancer and Fibroadenoma". Analysis of correlations between multiple SNPs associated with estrogen and breast cancer and fibroadenoma. They think they found something that increases risk 25 times. Study of 2500 people.
"Analysis of Telomere Length and Telomerase Activity in Tree Species of Various Lifespans, and with Age in the Bristlecone Pine Pinus longaeva". They compare telomere length and telomerase activity of bristlecone pines, which live for thousands of years to shorter lived trees. They think there's something there.
"Mitochondrial Dysfunction and Cell Senescence: Cause or Consequence?". Look at evidence of mitochondria's role in senescence. They say it's complicated. Sounds interesting but can't find it.
"Chromatin Modification and Senescence: Linkage by Tumor Suppressors?". Investigation of chromatin-modification path to senescence and potential genes involved. Maybe interesting.
Section 3: Neurodegeneration
"Amyloid-Beta Immunotherapy for the Prevention and Treatment of Alzheimer Disease: Lessons from Mice, Monkeys, and Humans". Seems to be a review of the experiments that have been performed in attacking amyloid beta through immunotherapy.
"Synaptic Pathology in the Brain Cortex of Old Monkeys as an Early Alteration in Senile Plaque Formation". Measurements of synaptic density in old monkeys compared to adult monkeys. I don't understand the measurements, except for the one where it says that the number of synapses per neuron go down by about 20% in the temporal cortex, but not in the frontal cortex.
"Membership in Genetic Groups Predicts Alzheimer Disease". Allele group analysis correlations with Alzheimer's. They think they found something with 800 times risk. 300 people in study.
"Level and Distribution of Microtubule- Associated Protein-2 (MAP2) as an Index of Dendritic Structural Dynamics". More comparison of measurements between the brains of old rats and adult rats that I don't understand.
"Association Between the HLA-A2 Allele and Alzheimer Disease". They find that 46% of their study group with AD have the HLA-A2 allele vs 38% of controls.
"Structural Synaptic Remodeling in the Perirhinal Cortex of Adult and Old Rats Following Object-Recognition Visual Training". And yet more measurements comparing synaptic densities in old and adult rats. This time, it is after the rats learn something.
"The nACHR4 594C/T Polymorphism in Alzheimer Disease". Analysis of correlations between variants of the neuronal nicotinic acetylcholine receptor and AD. Study of 140.
Section 4: Immunosenescence
"Immunorejuvenation in the Elderly". About possible ways to restore the immune system from its cytomegalovirus obsession by killing those T-cells, regrowing the thymus and hammering CMV with drugs. Sounds interesting but I can't find it.
"Antibody Quality in Old Age". So supposedly, the specificity of antibodies produced against antigens decreases with age. They think this is due to laxer selection in the germinal centers of mucosal tissue.
"Immunomodulatory Vaccines Against Autoimmune Diseases". Description of therapeutic vaccines against multiple sclerosis and myasthenia gravis, an autoimmune neuromuscular disease.
"A Novel Approach to Thymic Rejuvenation in the Aged". They implant cells that produce interleukin-7 into old thymus and it seems to help. Another one that sounds interesting but that I cannot find.
"Biology of Longevity: Role of the Innate Immune System". Seems to be a review of the links between the immune system and longevity. Could be interesting. Hard to tell from the abstract. Can't find it anyway.
"Memory B Cell Subpopulations in the Aged". Lower blood levels of IgD in the blood of old people, higher level of CD19+CD27+ memory cells. Negative correlation between the two. Too many memory cells, not enough naive.
"Analysis of Candidate Genes in Celiac Disease: A Tool to Identify Life-Threatening Associated Genes?" They find no difference in the frequencies of the transforming growth factor beta 2 alleles between celiac disease patients, healthy patients and healthy people over 95 year old.
"Analysis of HLA-DQA, HLA-DQB Frequencies in a Group of Sardinian Centenarians". No significant differences between observed and expected frequencies of HLA-DQA1 and HLA-DQB1 in centenarians.
Section 1: Stem Cells and Regeneration
"Conjecture: Can Continuous Regeneration Lead to Immortality? Studies in the MRL Mouse". Separate summary since I found the article and it sounded interesting
"Sustained Stromal Stem Cell Self-Renewal and Osteoblastic Differentiation During Aging". Characterisation of a line of stem cells isolated in bone marrow that can differentiate into all (?) other types. Frequency decreases from 0.01% of bone marrow cells when 3 years old to 0.0018% at 45 but doesn't go down after that. Interesting but probably too basic-sciency to incorporate.
"To Make a New Intestinal Mucosa". Grabbed some rats, chopped a quarter of their small intestine, making them leak bile in their shit, grabbed intestinal stem cells from newborn rats, and combined them with a separate bit of cleaned up section of intestine (from different rats I assume), and inserted the reformed bit at the end of their small intestines. Worked (as in no more bile leakage). They also did some other experiment with plastic scaffolds and being able to look at the implanted cells in vivo. It all sounds interesting.
"Transfection of CCE Mouse Embryonic Stem Cells with EGFP and BDNF Genes by the Electroporation Method". They show they can insert genes into stem cells by electroporation of plasmids and have them expressed.
"Glucose-Induced Replicative Senescence in Mesenchymal Stem Cells". Calorie restriction experiment in-vitro in which the mesenchymal stem cells which get less sugar die less and have higher replicative potential.
Section 2: Cancer, Cell Senescence, and Telomeres
"Gene Therapy That Safely Targets and Kills Tumor Cells Throughout the Body". Separate summary.
"Catechin-Vanilloid Synergies with Potential Clinical Applications in Cancer". Combination of two molecules inhibit expression of tNOX which is a molecule supposedly expressed only in cancers, and supposedly necessary for cancer growth.
"Multilocus Genotypes Spanning Estrogen Metabolism Associated with Breast Cancer and Fibroadenoma". Analysis of correlations between multiple SNPs associated with estrogen and breast cancer and fibroadenoma. They think they found something that increases risk 25 times. Study of 2500 people.
"Analysis of Telomere Length and Telomerase Activity in Tree Species of Various Lifespans, and with Age in the Bristlecone Pine Pinus longaeva". They compare telomere length and telomerase activity of bristlecone pines, which live for thousands of years to shorter lived trees. They think there's something there.
"Mitochondrial Dysfunction and Cell Senescence: Cause or Consequence?". Look at evidence of mitochondria's role in senescence. They say it's complicated. Sounds interesting but can't find it.
"Chromatin Modification and Senescence: Linkage by Tumor Suppressors?". Investigation of chromatin-modification path to senescence and potential genes involved. Maybe interesting.
Section 3: Neurodegeneration
"Amyloid-Beta Immunotherapy for the Prevention and Treatment of Alzheimer Disease: Lessons from Mice, Monkeys, and Humans". Seems to be a review of the experiments that have been performed in attacking amyloid beta through immunotherapy.
"Synaptic Pathology in the Brain Cortex of Old Monkeys as an Early Alteration in Senile Plaque Formation". Measurements of synaptic density in old monkeys compared to adult monkeys. I don't understand the measurements, except for the one where it says that the number of synapses per neuron go down by about 20% in the temporal cortex, but not in the frontal cortex.
"Membership in Genetic Groups Predicts Alzheimer Disease". Allele group analysis correlations with Alzheimer's. They think they found something with 800 times risk. 300 people in study.
"Level and Distribution of Microtubule- Associated Protein-2 (MAP2) as an Index of Dendritic Structural Dynamics". More comparison of measurements between the brains of old rats and adult rats that I don't understand.
"Association Between the HLA-A2 Allele and Alzheimer Disease". They find that 46% of their study group with AD have the HLA-A2 allele vs 38% of controls.
"Structural Synaptic Remodeling in the Perirhinal Cortex of Adult and Old Rats Following Object-Recognition Visual Training". And yet more measurements comparing synaptic densities in old and adult rats. This time, it is after the rats learn something.
"The nACHR4 594C/T Polymorphism in Alzheimer Disease". Analysis of correlations between variants of the neuronal nicotinic acetylcholine receptor and AD. Study of 140.
Section 4: Immunosenescence
"Immunorejuvenation in the Elderly". About possible ways to restore the immune system from its cytomegalovirus obsession by killing those T-cells, regrowing the thymus and hammering CMV with drugs. Sounds interesting but I can't find it.
"Antibody Quality in Old Age". So supposedly, the specificity of antibodies produced against antigens decreases with age. They think this is due to laxer selection in the germinal centers of mucosal tissue.
"Immunomodulatory Vaccines Against Autoimmune Diseases". Description of therapeutic vaccines against multiple sclerosis and myasthenia gravis, an autoimmune neuromuscular disease.
"A Novel Approach to Thymic Rejuvenation in the Aged". They implant cells that produce interleukin-7 into old thymus and it seems to help. Another one that sounds interesting but that I cannot find.
"Biology of Longevity: Role of the Innate Immune System". Seems to be a review of the links between the immune system and longevity. Could be interesting. Hard to tell from the abstract. Can't find it anyway.
"Memory B Cell Subpopulations in the Aged". Lower blood levels of IgD in the blood of old people, higher level of CD19+CD27+ memory cells. Negative correlation between the two. Too many memory cells, not enough naive.
"Analysis of Candidate Genes in Celiac Disease: A Tool to Identify Life-Threatening Associated Genes?" They find no difference in the frequencies of the transforming growth factor beta 2 alleles between celiac disease patients, healthy patients and healthy people over 95 year old.
"Analysis of HLA-DQA, HLA-DQB Frequencies in a Group of Sardinian Centenarians". No significant differences between observed and expected frequencies of HLA-DQA1 and HLA-DQB1 in centenarians.
Sunday, March 31, 2013
Gene Therapy That Safely Targets and Kills Tumor Cells Throughout the Body
Interestingness: 3
By Alicia Hurtado, Jen-Chieh Tseng, and Daniel Meruelo. Rejuvenation Research. Spring 2006, 9(1): 36-44. doi:10.1089/rej.2006.9.36.
I've heard about these cancer-killing viruses many times but I've never read one of the papers.
In this one, they injected cells from human ovarian cancer into mice, and after five days they started injecting them with a non-replicating version of the Sindbis virus. They modified the virus to also express green fluorescent protein (GFP) so they could also check that the bits that were green inside the mouse were the bits where in the tumours and not in the healthy tissue or in control mice that weren't injected with cancers. They also tried two other variants adding genes for interleukin-15 and -17 to the infected virus.
They claim that tumour sizes reduced in the places where the virus infected, and lifespan of the mice was extended, especially for the IL-15 and IL-17 versions. They don't show survival curves which is a pity. They also say that they weren't able to clear the tumours.
Their theory for specificity is that the cancer expresses higher amounts of laminin receptor (LAMR) and that the virus binds to it. LAMR is upregulated in many cancers. They tested the theory by blocking LAMR production through siRNA and saw the amount of virus infection drop in those cancers.
By Alicia Hurtado, Jen-Chieh Tseng, and Daniel Meruelo. Rejuvenation Research. Spring 2006, 9(1): 36-44. doi:10.1089/rej.2006.9.36.
I've heard about these cancer-killing viruses many times but I've never read one of the papers.
In this one, they injected cells from human ovarian cancer into mice, and after five days they started injecting them with a non-replicating version of the Sindbis virus. They modified the virus to also express green fluorescent protein (GFP) so they could also check that the bits that were green inside the mouse were the bits where in the tumours and not in the healthy tissue or in control mice that weren't injected with cancers. They also tried two other variants adding genes for interleukin-15 and -17 to the infected virus.
They claim that tumour sizes reduced in the places where the virus infected, and lifespan of the mice was extended, especially for the IL-15 and IL-17 versions. They don't show survival curves which is a pity. They also say that they weren't able to clear the tumours.
Their theory for specificity is that the cancer expresses higher amounts of laminin receptor (LAMR) and that the virus binds to it. LAMR is upregulated in many cancers. They tested the theory by blocking LAMR production through siRNA and saw the amount of virus infection drop in those cancers.
Thursday, March 28, 2013
Conjecture: Can Continuous Regeneration Lead to Immortality? Studies in the MRL Mouse
Interestingness: 2
By Ellen Heber-Katz, John Leferovich, Khamilia Bedelbaeva, Dmitri Gourevitch, and Lise Clark. Rejuvenation Research. Spring 2006, 9(1): 3-9. doi:10.1089/rej.2006.9.3.
Heber-Katz is the creator of the MRL mouse, which is a mouse with higher regeneration capabilities (regenerates chopped fingers, closes holes on ears and closes holes in their heart). They are trying to make some claim for it having longer longevity potential by making parallels with the hydra.
The hydra is a little (1 centimetre?) aquatic thing that probably doesn't age. It continuously produces cells from somewhere near the middle of the body. Those cells migrate to the extremities and die or bud off or just fall/float off. Their whole body gets replaced every 4 days. Their rate of cell reproduction and probability of death doesn't seem to change, at least for the few years that's been studied.
The parallel alluded to then is that of high cell generation/high cell death. In this paper, they show high cell generation in their injured hearts, and probably high cell death in a brain injury study.
By Ellen Heber-Katz, John Leferovich, Khamilia Bedelbaeva, Dmitri Gourevitch, and Lise Clark. Rejuvenation Research. Spring 2006, 9(1): 3-9. doi:10.1089/rej.2006.9.3.
Heber-Katz is the creator of the MRL mouse, which is a mouse with higher regeneration capabilities (regenerates chopped fingers, closes holes on ears and closes holes in their heart). They are trying to make some claim for it having longer longevity potential by making parallels with the hydra.
The hydra is a little (1 centimetre?) aquatic thing that probably doesn't age. It continuously produces cells from somewhere near the middle of the body. Those cells migrate to the extremities and die or bud off or just fall/float off. Their whole body gets replaced every 4 days. Their rate of cell reproduction and probability of death doesn't seem to change, at least for the few years that's been studied.
The parallel alluded to then is that of high cell generation/high cell death. In this paper, they show high cell generation in their injured hearts, and probably high cell death in a brain injury study.
Thursday, March 14, 2013
Issue 4, 2005
By the abstracts:
"Two Hands Make Light Work of Gene Modification". About a then new DNA-modification technique where they combined zinc-fingers and nucleases to chop the DNA wherever they wanted. The idea is to put a suitable replacement patch into the cell, and letting the cell's repair system patch the substitute in. A very similar idea has been making the rounds lately and has been advertised as an easier and cheaper version of the one used in this paper.
"Mitochondrial DNA Mutations, Apoptosis, and the Misfolded Protein Response" seems to be a theoretical paper postulating a mechanism explaining the results of experiments in mice with mutant mitochondrial DNA polymerase. They claim that the main way that mitochondrial mutations drive aging is that mutated proteins occasionally trigger apoptosis by interacting with mitochondrial membrane proteins. This then triggers compensatory effects of the tissue to this loss of cells. In the abstract they mention that heart tissue upregulates anti-apoptotic signals and also drives the rest of the surviving heart cells hard to compensate for pumping loss. In this model, ROS triggers the mtDNA mutations but is not a major part of the downstream mechanism (sort of the reverse of http://readingrejuvenationresearch.blogspot.com.au/2013/03/mitochondrial-microheteroplasmy-and.html, although very obviously related). I found a summary that looks to be an extract from the paper at http://crabsallover.blogspot.com.au/2006/11/mitochondrial-dna-mutations-apoptosis.html. I'll read the rest if I find it.
"Cellular Responses to Protein Accumulation Involve Autophagy and Lysosomal Enzyme Activation". Study of what happens when high level of protein gunk builds up on neurons in vitro. Lysosomes and macroautophagy are activated, but not enough to compensate.
"A Yang-Invigorating Chinese Herbal Formula Enhances Mitochondrial Functional Ability and Antioxidant Capacity in Various Tissues of Male and Female Rats". Chinese herbal formula upregulates SODs in rats.
"NANOG Changes in Mouse Kidneys with Age". Tracking of expression of NANOG, gene needed to keep pluripotency and one of the genes introduced to create iPSCs later, in mice's kidneys as they age. Expression goes down.
Also, there was a report on the 11th Congress of the International Association of Biomedical Gerontology which I'd like to read.
"Two Hands Make Light Work of Gene Modification". About a then new DNA-modification technique where they combined zinc-fingers and nucleases to chop the DNA wherever they wanted. The idea is to put a suitable replacement patch into the cell, and letting the cell's repair system patch the substitute in. A very similar idea has been making the rounds lately and has been advertised as an easier and cheaper version of the one used in this paper.
"Mitochondrial DNA Mutations, Apoptosis, and the Misfolded Protein Response" seems to be a theoretical paper postulating a mechanism explaining the results of experiments in mice with mutant mitochondrial DNA polymerase. They claim that the main way that mitochondrial mutations drive aging is that mutated proteins occasionally trigger apoptosis by interacting with mitochondrial membrane proteins. This then triggers compensatory effects of the tissue to this loss of cells. In the abstract they mention that heart tissue upregulates anti-apoptotic signals and also drives the rest of the surviving heart cells hard to compensate for pumping loss. In this model, ROS triggers the mtDNA mutations but is not a major part of the downstream mechanism (sort of the reverse of http://readingrejuvenationresearch.blogspot.com.au/2013/03/mitochondrial-microheteroplasmy-and.html, although very obviously related). I found a summary that looks to be an extract from the paper at http://crabsallover.blogspot.com.au/2006/11/mitochondrial-dna-mutations-apoptosis.html. I'll read the rest if I find it.
"Cellular Responses to Protein Accumulation Involve Autophagy and Lysosomal Enzyme Activation". Study of what happens when high level of protein gunk builds up on neurons in vitro. Lysosomes and macroautophagy are activated, but not enough to compensate.
"A Yang-Invigorating Chinese Herbal Formula Enhances Mitochondrial Functional Ability and Antioxidant Capacity in Various Tissues of Male and Female Rats". Chinese herbal formula upregulates SODs in rats.
"NANOG Changes in Mouse Kidneys with Age". Tracking of expression of NANOG, gene needed to keep pluripotency and one of the genes introduced to create iPSCs later, in mice's kidneys as they age. Expression goes down.
Also, there was a report on the 11th Congress of the International Association of Biomedical Gerontology which I'd like to read.
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