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).
Showing posts with label calorie restriction. Show all posts
Showing posts with label calorie restriction. Show all posts
Sunday, February 19, 2012
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.
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.
Saturday, January 22, 2011
Impact of Dietary Restriction on Brain Aging and Neurodegenerative Disorders: Emerging Findings from Experimental and Epidemiological Studies
Summary: Calorie restriction helps mice and rat models of Alzheimer's, Parkinson's and stroke. 2-doxyglucose does too.
Interestingness: 2
Paper by Mark P Mattson in the Journal of Anti-Aging Medicine, Volume 2, Issue 4, Winter 1999.
(((
Rats and mice models of Alzheimer's disease (AD) did better when they were on a calorie restriction diet (CR). The same for Parkinson's disease (PD). Also for Huntington disease (HD). Also for rats given a stroke. I don't like the models, except the one for stroke, so I don't care much about these results.
They think this effect comes from over-expression of heat shock proteins (HSP-70) when glucose goes low. When given 2-deoxygluose (2-DG), a modified glucose that competes with glucose for the energy chain enzymes but is not able to be broken down properly (http://readingrejuvenationresearch.blogspot.com/2010/07/2-deoxy-d-glucose-feeding-in-rats.html), rats and mice also did better in the AD, PD and stroke models, even though they lived under all-you-can eat buffet conditions.
Finally, some lame-sounding correlation studies between caloric intake surveys with PD, AD and stroke are listed.
)))
Abstract follows:
Interestingness: 2
Paper by Mark P Mattson in the Journal of Anti-Aging Medicine, Volume 2, Issue 4, Winter 1999.
(((
Rats and mice models of Alzheimer's disease (AD) did better when they were on a calorie restriction diet (CR). The same for Parkinson's disease (PD). Also for Huntington disease (HD). Also for rats given a stroke. I don't like the models, except the one for stroke, so I don't care much about these results.
They think this effect comes from over-expression of heat shock proteins (HSP-70) when glucose goes low. When given 2-deoxygluose (2-DG), a modified glucose that competes with glucose for the energy chain enzymes but is not able to be broken down properly (http://readingrejuvenationresearch.blogspot.com/2010/07/2-deoxy-d-glucose-feeding-in-rats.html), rats and mice also did better in the AD, PD and stroke models, even though they lived under all-you-can eat buffet conditions.
Finally, some lame-sounding correlation studies between caloric intake surveys with PD, AD and stroke are listed.
)))
Abstract follows:
Although dietary restriction (DR) extends life span and reduces levels of cellular oxidative stress in several different organ systems of laboratory rodents and monkeys, its impact on the brain is unknown. As is the case with age-related disorders in other organ systems (e.g., cardiovascular disease, diabetes, and many cancers), neurodegenerative disorders such as Alzheimer disease (AD), Parkinson disease (PD), and stroke involve increased levels of cellular oxidative stress and metabolic compromise. Recent studies of experimental rat and mouse models of AD, PD, and stroke have shown that DR increases resistance of neurons to dysfunction and degeneration. DR can attenuate age-related and disease-specific deficits in cognitive and motor functions in rodents. The available data suggest at least two possible mechanisms whereby DR protects neurons. One involves decreased levels of mitochondrial oxyradical production, and the second involves induction of the expression of "stress proteins" and neurotrophic factors. The latter mechanism is supported by data showing that the neuroprotective effect of DR can be mimicked by administration of 2-deoxyglucose to animals fed ad libitum. Recent findings in epidemiological studies of human populations suggest that individuals with a low daily calorie intake have reduced risk for AD and PD. Collectively, the available data suggest that DR may prove beneficial in reducing both the incidence and severity of neurodegenerative disorders in humans.
Monday, November 1, 2010
Recovery of Circadian Body Temperature in Aged Persons
Summary: Some body temperature measurements of old people, with some rising
Interestingness: 1
Paper by Iwao Hirosawa, Susumu Iwamoto, Junko Yoneda, Yasuhiko Wada and Akio Koizumi in the Journal of Anti-Aging Medicine, Volume 2, Issue 2, Summer 1999.
(((
They measured the temperature of 10 old people that were put into aged care, mostly after having a stroke. They measured many times a day for about a year. In their analysis, they split the people into two groups, the first one, consisting of four people, in which their temperature went up after they entered the care place, and the other of the remaining six, whose temperature didn't go up. Their summary says that maybe the people in the first group were under caloric restriction prior to entering, which got fixed once entering, thus raising their temperature. From the weight numbers, they were probably all borderline CR anyway (40 kg for women, 43 for men, 1.40 and 1.49 metres. Small people). The graphs are not clear to me. It isn't clear either whether the rise in temperature for those four people was a good or bad thing.
There is some further analysis of seasonal changes split across time of day, but I don't understand what it showed
)))
Abstract follows:
Interestingness: 1
Paper by Iwao Hirosawa, Susumu Iwamoto, Junko Yoneda, Yasuhiko Wada and Akio Koizumi in the Journal of Anti-Aging Medicine, Volume 2, Issue 2, Summer 1999.
(((
They measured the temperature of 10 old people that were put into aged care, mostly after having a stroke. They measured many times a day for about a year. In their analysis, they split the people into two groups, the first one, consisting of four people, in which their temperature went up after they entered the care place, and the other of the remaining six, whose temperature didn't go up. Their summary says that maybe the people in the first group were under caloric restriction prior to entering, which got fixed once entering, thus raising their temperature. From the weight numbers, they were probably all borderline CR anyway (40 kg for women, 43 for men, 1.40 and 1.49 metres. Small people). The graphs are not clear to me. It isn't clear either whether the rise in temperature for those four people was a good or bad thing.
There is some further analysis of seasonal changes split across time of day, but I don't understand what it showed
)))
Abstract follows:
The human diurnal body temperature rhythm does not differ significantly between aged and young subjects; the amplitude and mean level, however, decrease with age. In order to know whether the core body temperature of disabled elderly persons was influenced by environmental factors, we measured the tympanic temperature of nursing home patients. In 4 of 10 tested patients, there was a statistically significant upward shift of the core body temperature within 1 month of admission (P < 0.05). This restoration of body temperature was observed to occur without any relationship to the season of admission. The amplitude of circadian body temperature did not change. There were significant seasonal variations in the diurnal body temperature range between summer and winter, especially between 0900 and 1100 hours in 5 persons with, and without, an upward shift of body temperature. The persons who recovered their body temperatures were thought to have been had lower-than-normal-body temperature for age prior to admission. Body temperature recovery after admission may have been caused by an improvement in energy intake and nutritional balance.
Sunday, June 27, 2010
Calorie Restriction in Nonhuman Primates: Implications for Age-Related Disease Risk
Summary: Calorie restriction (CR) probably reduces diabetes and heart disease markers in rhesus monkeys. It also probably maintains DHEAS levels.
Interestingness: 3
Paper by Mark A Lane, Angela Black, Donald K Ingram and George S Roth in the Journal of Anti-Aging Medicine, Volume 1, Issue 4, Winter 1998.
(((I had already read a follow up paper published in 2010, so I knew the movie continued to go relatively well, but not fantastically so. That detracted from the excitement. This paper focuses on the effects of CR on diabetes and cardiovascular disease, and by measuring biomarkers in the latter case. Mortality would have been more interesting, but most likely the numbers would have been too low at such an early stage of the study. In any case, since CR seems to be the only "easy" intervention to make a difference for now, it's still a relatively interesting read.)))
Calorie restriction (CR) (((lowering food calorie intake by about 30% while maintaining good nutrition))) extends lifespan in lots of short-lived species, including rotifers (((little water animals, about half a milimetre long))), water fleas (((same))), fish, spiders, hamsters, mice and rats. Doing the relevant controlled experiment in humans would be tricky and take a long time. Doing it on rhesus monkeys is a close approximation and until animal-liberationists bomb them, less problematic.
Four experiments are reviewed. Two proper long-term randomised control studies on groups of 200 and 80 monkeys, the first one (NIA) in its 12th year, starting on sets of 1-2 year olds, 3-5 year olds and of > 17 year old monkeys, and the second one (UW) on 8-14 year old monkeys (((lifespan of rhesus monkeys is around 40 years))). One of the others (BGWF) is a short term (4 years) study on the cardiovascular effects of CR on 32 8-year old crab-eating macaques, the study being in its second year. The final study (UMB) is on 8 weight-stabilised rhesus monkeys which by coincidence happened to have a food regime similar to CR monkeys.
From the NIA study, the following effects are seen on the monkeys:
Decreases in:
Increases in:
No changes in:
All of these agree with rodent CR studies, in the cases where the rodent data is available, except for the lymphocyte calcium response.
(((That could really do as a summary, but the paper had another eight pages to go)))
With regards to diabetes and glucose regulation, there is another handy table summarising all the studies:
Both big studies agree in all of the following results:
The small coincidental study disagrees with regards to fasting glucose and glucose tolerance, and the short term study with respect to fasting insulin.
The effect of CR on cardiovascular disease doesn't appear to be as clearly beneficial. While triglyceride levels decreased the effect on LDL, HDL and total cholesterol was not statistically significant. By analysing HDL fractions, an increase in HDL2B levels was measured. In the female subset of monkeys, lower total cholesterol and blood pressure was measured in CR monkeys compared to control monkeys. Lower arterial stiffness was also measured in male CR monkeys.
(((A graph at the end shows lower rate of decline of DHEAS (dehydroepiandrosterone-sulfate) in male CR monkeys, which would probably be the most interesting part of the paper. The framing of the graph seems a bit too purposeful though (why only show 3 years between 6 and 9 years of age?) )))
Abstract follows:
Interestingness: 3
Paper by Mark A Lane, Angela Black, Donald K Ingram and George S Roth in the Journal of Anti-Aging Medicine, Volume 1, Issue 4, Winter 1998.
(((I had already read a follow up paper published in 2010, so I knew the movie continued to go relatively well, but not fantastically so. That detracted from the excitement. This paper focuses on the effects of CR on diabetes and cardiovascular disease, and by measuring biomarkers in the latter case. Mortality would have been more interesting, but most likely the numbers would have been too low at such an early stage of the study. In any case, since CR seems to be the only "easy" intervention to make a difference for now, it's still a relatively interesting read.)))
Calorie restriction (CR) (((lowering food calorie intake by about 30% while maintaining good nutrition))) extends lifespan in lots of short-lived species, including rotifers (((little water animals, about half a milimetre long))), water fleas (((same))), fish, spiders, hamsters, mice and rats. Doing the relevant controlled experiment in humans would be tricky and take a long time. Doing it on rhesus monkeys is a close approximation and until animal-liberationists bomb them, less problematic.
Four experiments are reviewed. Two proper long-term randomised control studies on groups of 200 and 80 monkeys, the first one (NIA) in its 12th year, starting on sets of 1-2 year olds, 3-5 year olds and of > 17 year old monkeys, and the second one (UW) on 8-14 year old monkeys (((lifespan of rhesus monkeys is around 40 years))). One of the others (BGWF) is a short term (4 years) study on the cardiovascular effects of CR on 32 8-year old crab-eating macaques, the study being in its second year. The final study (UMB) is on 8 weight-stabilised rhesus monkeys which by coincidence happened to have a food regime similar to CR monkeys.
From the NIA study, the following effects are seen on the monkeys:
Decreases in:
- Body weight
- Fat and lean mass
- Trunk to leg fat ratio
- Fasting glucose/insulin
- Metabolic rate (short term)
- Body temperature
- Triglycerides
- IGF-1/growth hormone
- IL-6
- Rate of decline of DHEAS
- Lymphocyte number
Increases in:
- Insulin sensitivity
- HDL2B
- Time to sexual maturation
- Time to skeletal maturation (((table says opposite on these last two, but text is clearer)))
No changes in:
- Metabolic rate (long term)
- Locomotion
- Testosterone
- Estradiol, LH, FSH, Progesterone
- Wound closure rate
- Clonal proliferation
- Beta-galactidase senescent cells
- Lymphocyte calcium response
All of these agree with rodent CR studies, in the cases where the rodent data is available, except for the lymphocyte calcium response.
(((That could really do as a summary, but the paper had another eight pages to go)))
With regards to diabetes and glucose regulation, there is another handy table summarising all the studies:
Both big studies agree in all of the following results:
- Decrease in fasting glucose
- Decrease in fasting insulin
- Decrease in insulin response
- Increase in insulin sensitivity
- No increase in glucose tolerance
The small coincidental study disagrees with regards to fasting glucose and glucose tolerance, and the short term study with respect to fasting insulin.
The effect of CR on cardiovascular disease doesn't appear to be as clearly beneficial. While triglyceride levels decreased the effect on LDL, HDL and total cholesterol was not statistically significant. By analysing HDL fractions, an increase in HDL2B levels was measured. In the female subset of monkeys, lower total cholesterol and blood pressure was measured in CR monkeys compared to control monkeys. Lower arterial stiffness was also measured in male CR monkeys.
(((A graph at the end shows lower rate of decline of DHEAS (dehydroepiandrosterone-sulfate) in male CR monkeys, which would probably be the most interesting part of the paper. The framing of the graph seems a bit too purposeful though (why only show 3 years between 6 and 9 years of age?) )))
Abstract follows:
Calorie restriction (CR)—undernutrition without malnutrition—ranks among the most reproducible and widely used research paradigms in gerontologic research. This intervention is the only manipulation that has been shown consistently to extend the life span, delay onset and slow tumor progression, and retard physiologic aging in many systems. A large body of literature exists documenting these remarkable effects in such diverse short-lived species as rotifers, water fleas, fish, spiders, hamsters, and laboratory mice and rats. However, it is not known if CR has similar effects in longer-lived species more closely related to humans. Two major studies in rhesus monkeys, one at the National Institute on Aging and the other at the University of Wisconsin, were begun several years ago to address this question. Two similar studies focusing mostly on disease end points such as obesity, diabetes, and cardiovascular disease are also underway at the University of Maryland and Bowman-Gray School of Medicine. These studies have clearly shown that most physiologic responses assessed in monkeys on CR parallel the extensive literature on rodents. This article focuses on data related to various risk factors for age-associated diseases, in particular diabetes and cardiovascular disease. Although it will be several more years before definitive results regarding life span are available, emerging data from the monkey studies strongly suggest that CR alters several disease risk factors and may affect postmaturational aging in some systems. Therefore, it is likely that this nutritional intervention will result in at least moderate increases in the primate life span related to amelioration of certain age-related diseases and their complications.
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