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.
Showing posts with label mouse. Show all posts
Showing posts with label mouse. Show all posts
Sunday, March 31, 2013
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.
Tuesday, February 5, 2013
Extension of Murine Life Span by Overexpression of Catalase Targeted to Mitochondria
Interestingness: 7
tl;dr 20% lifespan increase from mitochondrially hyperexpressed catalase
By Samuel E Schriner, Nancy J Linford, George M Martin,Piper Treuting, Charles E Ogburn, Mary Emond, Pinar E Coskun, Warren Ladiges, Norman Wolf, Holly Van Remmen, Douglas C Wallace and Peter S Rabinovitch in Science 308, 1909 (2005). doi: 10.1126/science.1106653
This was not published in Rejuvenation Research. It was published in Science. It was commented about by Richard Cutler in issue 3 of 2005 of Rejuvenation Research, but I couldn't find access to the comments. I did find this one though, and since it is a pretty famous result, I read it.
They overexpressed human catalase in mice in six separate lineages, two in their peroxisome, two in their nucleus and two in their mitochondria. That is, there are four different mice lineages per experiment, two for controls, and two with the intervention, one corresponding to each of the controls. They show results per lineage with respect to their corresponding control, and I'll write them down like that too since I can't think of a better way. In all cases, the amount of catalase expressed is very high compared to wild type.
Going by the graphs, control median lifespan was about 26-27 months, and maximum lifespan (age at 10% survival, not average lifespan of top 10% like they measure in the paper (because I don't have the raw data)) at around 33 months. Expression in the nucleus extended median lifespan by 1 and 3 months (p > 0.05) with no increase in maximum lifespan. Expression in the peroxisome increased median by 3 (p > 0.05) and 3.5 months (p < 0.02) with no increase in maximum. Expression in the mitochondria increased median by 4.5 months (p < 0.0001) and 5.5 months (p < 0.0002) with maximum lifespan increases of 4.5 months (p < 0.001 combined lineages)
Most of the paper focuses on the mitochondrial branch since it's the most impressive. In the mitochondrial branch, there's equivalent lifespan increases for males and females. They also observe lots of good shit happening to the heart (less heart disease in general).
In what seems like a side-experiment they cross the peroxisome-expressing mice with a superoxide-dismutase expressing mice, and they get a 18.5% (p < 0.0001) median life extension with respect to wild type and 7% (p=0.036) compared to the peroxisome mice, but no maximum life extension. They note that the mitochondrially expressing mice would be a better one to try.
By the way, superoxide anion O2- goes to hydrogen peroxide H2O2 helped by superoxide dismutase. Hydrogen peroxide goes hammertime unless defused by catalase (or glutathione peroxidase).
tl;dr 20% lifespan increase from mitochondrially hyperexpressed catalase
By Samuel E Schriner, Nancy J Linford, George M Martin,Piper Treuting, Charles E Ogburn, Mary Emond, Pinar E Coskun, Warren Ladiges, Norman Wolf, Holly Van Remmen, Douglas C Wallace and Peter S Rabinovitch in Science 308, 1909 (2005). doi: 10.1126/science.1106653
This was not published in Rejuvenation Research. It was published in Science. It was commented about by Richard Cutler in issue 3 of 2005 of Rejuvenation Research, but I couldn't find access to the comments. I did find this one though, and since it is a pretty famous result, I read it.
They overexpressed human catalase in mice in six separate lineages, two in their peroxisome, two in their nucleus and two in their mitochondria. That is, there are four different mice lineages per experiment, two for controls, and two with the intervention, one corresponding to each of the controls. They show results per lineage with respect to their corresponding control, and I'll write them down like that too since I can't think of a better way. In all cases, the amount of catalase expressed is very high compared to wild type.
Going by the graphs, control median lifespan was about 26-27 months, and maximum lifespan (age at 10% survival, not average lifespan of top 10% like they measure in the paper (because I don't have the raw data)) at around 33 months. Expression in the nucleus extended median lifespan by 1 and 3 months (p > 0.05) with no increase in maximum lifespan. Expression in the peroxisome increased median by 3 (p > 0.05) and 3.5 months (p < 0.02) with no increase in maximum. Expression in the mitochondria increased median by 4.5 months (p < 0.0001) and 5.5 months (p < 0.0002) with maximum lifespan increases of 4.5 months (p < 0.001 combined lineages)
Most of the paper focuses on the mitochondrial branch since it's the most impressive. In the mitochondrial branch, there's equivalent lifespan increases for males and females. They also observe lots of good shit happening to the heart (less heart disease in general).
In what seems like a side-experiment they cross the peroxisome-expressing mice with a superoxide-dismutase expressing mice, and they get a 18.5% (p < 0.0001) median life extension with respect to wild type and 7% (p=0.036) compared to the peroxisome mice, but no maximum life extension. They note that the mitochondrially expressing mice would be a better one to try.
By the way, superoxide anion O2- goes to hydrogen peroxide H2O2 helped by superoxide dismutase. Hydrogen peroxide goes hammertime unless defused by catalase (or glutathione peroxidase).
Saturday, September 25, 2010
Characterization of the Age Changes in Brain and Liver Enzymes of Senescence-Accelerated Mice (SAM)
Summary: Some enzymes and neurotransmitters have different activity in mice models of accelerated aging.
Interestingness: 1
Paper by E Bulygina, S Gallant, G Kramarenko, S Stvolinsky, M Yuneva and A Boldyrev in the Journal of Anti-Aging Medicine, Volume 2, Issue 1, Spring 1999.
(((
In senescence accelerated mice, prone 1 (SAMP1) compared to senescence accelerated mice, resistant 1 (SAMR1):
In all of the above, young is 4 months, age tracking goes from 8-12 months. SAMP1 mice die around then.
)))
Abstract follows:
Interestingness: 1
Paper by E Bulygina, S Gallant, G Kramarenko, S Stvolinsky, M Yuneva and A Boldyrev in the Journal of Anti-Aging Medicine, Volume 2, Issue 1, Spring 1999.
(((
In senescence accelerated mice, prone 1 (SAMP1) compared to senescence accelerated mice, resistant 1 (SAMR1):
- Mono-amine oxide b (MAOb) activity in the brain goes up as it ages. In SAMR1 it stays put.
- Glutamate binding in N-methyl-D-aspartic acid (NMDA) receptors starts much lower in young mice, but climbs to be much higher as it ages
- Na/K ATPase activity in the brain goes up as it ages.
- Cytochrome P450 activity in the liver is consitently higher
In all of the above, young is 4 months, age tracking goes from 8-12 months. SAMP1 mice die around then.
)))
Abstract follows:
The comparative neurochemical characteristics of brain and liver membranes of senescence-accelerated mice, prone (SAMP1) and senescence-accelerated mice, resistant (SAMR1) strains were evaluated using males and females of several ages. Abnormal N-methyl-D-aspartic acid (NMDA) binding and monoamine oxidase b activity in SAMP brain membranes may promote increased accumulation of reactive oxygen species (ROS) in neurons. Na/K-adinosine triphosphatase (ATPase) and liver cytochrome P450 activities are greater in SAMP1 neurons than in SAMR1 neurons, which may reflect an adaptive tissue response to ROS accumulation.
Sunday, January 10, 2010
Interventions of Senescence in SAM Mice
Summary: Description of effects of many substances on various diseases on mice that age fast.
Paper by Masanory Hosokawa, Makiko Umezawa, Keiichi Higuchi and Toshio Takeda in Journal of Anti-Aging Medicine, Volume 1, Number 1, 1998.
(((bias: I don't pay much attention to mice as models of aging. I pay even less attention to accelerated-aging mice as models of aging. They seem too far removed. I also know squat about the subject)))
Most of the paper describes the Senescence accelerated mouse prone and resistant (SAMP and SAMR) variety of mice developed since the late 60s. They are closely related, and are both relatively normal until they reach maturity (((don't know when that is, but they become fertile at around 45 days))). After maturity, SAMR continues a relatively normal mouse life, but SAMP deteriorates rapidly in many different ways. Median life-span of SAMR mice is about the same as normal long-lived mice, although not the ones in their lab, which lived for around 19 months. Median life-span for SAMP mice varied between about 7 and 14 months depending on the sub-variety. They also use a degree-of-senescence score that is just how fucked they think the mouse is, and note a factor of 1.5-3.5 greater degree of senescence in SAMP mice over SAMR at 8 months of age. SAM mice, both varieties, tend to die from contracted kidneys, abscess formation (((balls of pus!?))), pneumonia and lymphomas (((not similar to the profile in humans))). The idea is that the SAMP is just an accelerated decline version of the SAMR.
It then describes a few sub-variants of the SAMP mice that are specially prone to osteoperosis, learning and memory problems, amyloidosis (((insoluble protein clumps in various organs))) and immune system decline.
It finishes with things they tried that helped with each one of those. Caloric restriction helped with the lifespan and the amyloidosis of SAMP mice (no measurement numbers given) (((Most interesting for me is that it didn't extend the SAMR lifespan))). Summary of the rest of the benefits found is as follows (no numbers are given for any of these):
Soy bean protein instead of casein for amyloidosis, aged garlic extract helped survival ratio of the sub-variety with problems with memory and immune-system (SAMP8). Toki-Shakuyaku-San (TSS) and Boui-Jiou-Tou (BJT) extended median survival of the amyloidosis prone mice (SAMP1). Deer antler (((!?!))) orally increased testosterone, decreased malondialdehyde (((a oxidative stress marker))) in the liver and brain, increased RNA and protein in the liver, increased liver super-oxide simutase, decreased monoamine oxidase B in liver and brain in SAMP8 males. Alpha-phenyl N-tertiary-butyl nitrone (PBN, a spin-trapping agent) (((free-radical capture))) increased lifespan of SAMP8. Acidic fibroblast growth factor (aFGF) protected the impairment of delayed type hypersensitivity reaction in SAMP8.
The osteoperosis-prone variety (SAMP6) was helped by mixing its bone marrow with those of another sub-variety, or getting bone marrow-derived factors from that other sub-variety, or by giving it calcium, parathyroid hormone or estrogen.
(((I'll skip the substances that helped memory and learning since I consider them even less relevant to humans than the others, but there's a lot of them, so read the article if you are interested)))
(((Conclusion: mice with mutations that make them age fast can be successfully helped with lots of substances. I wouldn't expect much of it to transfer to humans)))
Abstract follows:
Paper by Masanory Hosokawa, Makiko Umezawa, Keiichi Higuchi and Toshio Takeda in Journal of Anti-Aging Medicine, Volume 1, Number 1, 1998.
(((bias: I don't pay much attention to mice as models of aging. I pay even less attention to accelerated-aging mice as models of aging. They seem too far removed. I also know squat about the subject)))
Most of the paper describes the Senescence accelerated mouse prone and resistant (SAMP and SAMR) variety of mice developed since the late 60s. They are closely related, and are both relatively normal until they reach maturity (((don't know when that is, but they become fertile at around 45 days))). After maturity, SAMR continues a relatively normal mouse life, but SAMP deteriorates rapidly in many different ways. Median life-span of SAMR mice is about the same as normal long-lived mice, although not the ones in their lab, which lived for around 19 months. Median life-span for SAMP mice varied between about 7 and 14 months depending on the sub-variety. They also use a degree-of-senescence score that is just how fucked they think the mouse is, and note a factor of 1.5-3.5 greater degree of senescence in SAMP mice over SAMR at 8 months of age. SAM mice, both varieties, tend to die from contracted kidneys, abscess formation (((balls of pus!?))), pneumonia and lymphomas (((not similar to the profile in humans))). The idea is that the SAMP is just an accelerated decline version of the SAMR.
It then describes a few sub-variants of the SAMP mice that are specially prone to osteoperosis, learning and memory problems, amyloidosis (((insoluble protein clumps in various organs))) and immune system decline.
It finishes with things they tried that helped with each one of those. Caloric restriction helped with the lifespan and the amyloidosis of SAMP mice (no measurement numbers given) (((Most interesting for me is that it didn't extend the SAMR lifespan))). Summary of the rest of the benefits found is as follows (no numbers are given for any of these):
Soy bean protein instead of casein for amyloidosis, aged garlic extract helped survival ratio of the sub-variety with problems with memory and immune-system (SAMP8). Toki-Shakuyaku-San (TSS) and Boui-Jiou-Tou (BJT) extended median survival of the amyloidosis prone mice (SAMP1). Deer antler (((!?!))) orally increased testosterone, decreased malondialdehyde (((a oxidative stress marker))) in the liver and brain, increased RNA and protein in the liver, increased liver super-oxide simutase, decreased monoamine oxidase B in liver and brain in SAMP8 males. Alpha-phenyl N-tertiary-butyl nitrone (PBN, a spin-trapping agent) (((free-radical capture))) increased lifespan of SAMP8. Acidic fibroblast growth factor (aFGF) protected the impairment of delayed type hypersensitivity reaction in SAMP8.
The osteoperosis-prone variety (SAMP6) was helped by mixing its bone marrow with those of another sub-variety, or getting bone marrow-derived factors from that other sub-variety, or by giving it calcium, parathyroid hormone or estrogen.
(((I'll skip the substances that helped memory and learning since I consider them even less relevant to humans than the others, but there's a lot of them, so read the article if you are interested)))
(((Conclusion: mice with mutations that make them age fast can be successfully helped with lots of substances. I wouldn't expect much of it to transfer to humans)))
Abstract follows:
The Senescence-Accelerated Mouse (SAM) strain was established in the Department of Senescence Biology, Chest Disease Research Institute, Kyoto University, as a novel murine model of senescence acceleration and age-associated disorders. This strain is actually a group of related inbred strains (recombinant inbred strain-like) including nine strains of accelerated senescence-prone, short-lived mice (SAMP) and three strains of accelerated senescence-resistant, long-lived mice (SAMR). Each SAMP strain shows relatively strain-specific age-associated pathologies. These characteristic pathological phenotypes are similar to those often observed in elder humans. They include senile osteoporosis, osteoarthritis, age-related deficits in learning and memory with/without forebrain atrophy, presbycusis, senile amyloidosis, age-related impairment of the immune response, and so on. The common aging characteristic of SAMP strains is senescence acceleration after normal development and maturation. We have made attempts to intervene the senescence acceleration and specifically in these pathologies: senile osteoporosis and the age-related deficits in learning and memory. These attempts, including caloric restriction, administration of nutrients, chemicals and traditional herbal medicines, show beneficial effects on the aging process of these mice. Similar interventions may prevent or control the onset and progress of age-associated disorders in other species and may have clinical relevance for humans.
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