Re: Re: Severe calorie restriction reduces aging-related cell damage

[Guest guest]

Thanks very much, Dave,

I'm a little puzzled about the wording in the first: " reversal in two of three previously reported biomarkers of longevity (fasting insulin level and core body temperature)… ", though.

The second I guess clears it up.

But the main thing that puzzles me, is that obese people apparently experience a lower core temp also.

I'm back down to 98.2 deg today, having dropped the excess protein. I don't feel uncomfortably cold. I wonder if there's a magic level of say 98.0 (average of 97.4 and 98.6)that provides a compromise?

Just wondering - 97.4 is cold in the winter.

Regards.

[ ] Re: Severe calorie restriction reduces aging-related cell damage

Diane,I was just reading about this in another publication. Besidesreducing cell damage, CR also improved 2 other biomarkers:"Our results indicate that prolonged calorie restriction caused areversal in two of three previously reported biomarkers of longevity(fasting insulin level and core body temperature)… and a reduction inDNA fragmentation, reflecting less DNA damage," wrote lead authorLeonie Heilbronn from Louisiana State University.Another write-up on Nutraingredients.com, and the abstract from JAMAis copied below.Dave++++++++++++++++++http://www.nutraingredients.com/news/ng.asp?n=66877 & m=1NIE405 & c=lqeudkujayvvlpcCalorie-restricted diet could slow aging05/04/2006- Restricting your intake of calories may not only helppeople live longer, as well as losing weight, say the scientistsbehind a clinical trial.Previous studies have reported that calorie-restricted diets couldprolong the lives of rodents and other short-lived species, but, untilnow, no such human study has been undertaken to investigate theeffects of such diets on markers of human aging.The Comprehensive Assessment of the Long Term Effects of ReducingIntake of Energy (CALERIE) study, published in the new issue of theJournal of the American Medical Association (Vol. 295, pp. 1539-1548),followed 48 middle-aged, overweight, non-obese men and women eatingone of four calorie-controlled diets for six months.The participants (21 men, 27 women) were randomly assigned to eat oneof four diets: control (weight maintenance diet); calorie restriction(calorie intake reduced by 25 per cent of normal); calorie restrictionwith exercise (calorie intake reduced by 12.5 per cent, energyexpenditure increased by 12.5 per cent); very low-calorie diet (890kilocalories per day until 15 per cent weight loss and then weightmaintenance diet).After six months, the control group had a measured weight loss ofabout 1 per cent. The three intervention groups, as expected, lostsignificantly more weight. Both the calorie restriction and calorierestriction with exercise groups lost about 10 per cent during thetrial, while the low-calorie group lost on average 14 per cent, inkeeping with the design study.Weight loss was not the primary focus of the study however, andpositive results for the calorie restriction were observed for markersof aging."Our results indicate that prolonged calorie restriction caused areversal in two of three previously reported biomarkers of longevity(fasting insulin level and core body temperature)… and a reduction inDNA fragmentation, reflecting less DNA damage," wrote lead authorLeonie Heilbronn from Louisiana State University."We are the first to report a significant decline in DNA damagefollowing six months of calorie restriction in non-obese men andwomen," stressed Heilbronn.One of the most widely accepted theories on aging is that reactiveoxygen species (ROS) attack, amongst other things, DNA, affect normalcell function and lead to again and, potentially, the development ofcancer.No changes were recorded in other markers of longevity, includingdehydroepiandrosterone sulfate (DHEAS) levels, or in fasting glucoselevels, which have been measured in both primates and longer-livedmen, an inconsistency suggested to be due to the short duration of theCALERIE study.Interestingly, a `metabolic adaptation' (a change in the use ofenergy) was observed and occurred in the first three months of thetrial, with no further changes at the end of the trial."The metabolic adaptation in the calorie restriction with exercisegroup was similar to that observed in the calorie restriction group,suggesting that energy deficit rather than calorie restriction itselfis driving the decrease in energy expenditure," said Heilbronn.In an accompanying editorial, Luigi Fontana from Washington UniversitySchool of Medicine welcomed the study as adding a considerable amountof information to the current understanding of the subject."It is anticipated that the study by Heilbronn et al will stimulateadditional investigation of the effects of calorie restriction inhumans," said Fontana.Dr. Fontana called for longer-term studies with larger samplepopulations to measure changes to hormones, metabolism and geneexpression caused by such diets."Although it is not likely that many individuals would adopt acalorie-restricted diet, the value of these studies is that theysuggest possible mechanisms of aging in humans and points ofintervention to modify the effects of aging," concluded Fontana.The call for more study was echoed by Helen Stracey, a registereddietitian on behalf of the British Dietetic Association."It is true that calorie restriction increases longevity in rats, thishas been proved," Stracey told NutraIngredients.com."This study is in humans but unfortunately the sample size is toosmall (46 people counting the drop outs) for us to conclude anythingand in particular extrapolate anything to the general population. Theconclusion is that larger studies of longer duration are needed todetermine if calorie restriction attenuates the aging process."http://jama.ama-assn.org/cgi/content/abstract/295/13/1539?maxtoshow= & HITS=10 & hits=10 & RESULTFORMAT= & fulltext=calerie & searchid=1 & FIRSTINDEX=0 & resourcetype=HWCITEffect of 6-Month Calorie Restriction on Biomarkers of Longevity,Metabolic Adaptation, and Oxidative Stress in Overweight IndividualsA Randomized Controlled TrialLeonie K. Heilbronn, PhD; Lilian de Jonge, PhD; Madlyn I. Frisard,PhD; P. DeLany, PhD; D. Enette Larson-Meyer, PhD; Rood,PhD; Tuong Nguyen, BSE; Corby K. , PhD; Volaufova, PhD; M. Most, PhD; L. Greenway, PhD; R. , MD;Walter A. Deutsch, PhD; A. on, PhD; Ravussin, PhD;for the Pennington CALERIE TeamJAMA. 2006;295:1539-1548.Context Prolonged calorie restriction increases life span in rodents.Whether prolonged calorie restriction affects biomarkers of longevityor markers of oxidative stress, or reduces metabolic rate beyond thatexpected from reduced metabolic mass, has not been investigated in humans.Objective To examine the effects of 6 months of calorie restriction,with or without exercise, in overweight, nonobese (body mass index, 25to <30) men and women.Design, Setting, and Participants Randomized controlled trial ofhealthy, sedentary men and women (N = 48) conducted between March 2002and August 2004 at a research center in Baton Rouge, La.Intervention Participants were randomized to 1 of 4 groups for 6months: control (weight maintenance diet); calorie restriction (25%calorie restriction of baseline energy requirements); calorierestriction with exercise (12.5% calorie restriction plus 12.5%increase in energy expenditure by structured exercise); verylow-calorie diet (890 kcal/d until 15% weight reduction, followed by aweight maintenance diet).Main Outcome Measures Body composition; dehydroepiandrosteronesulfate (DHEAS), glucose, and insulin levels; protein carbonyls; DNAdamage; 24-hour energy expenditure; and core body temperature.Results Mean (SEM) weight change at 6 months in the 4 groups was asfollows: controls, –1.0% (1.1%); calorie restriction, –10.4% (0.9%);calorie restriction with exercise, –10.0% (0.8%); and very low-caloriediet, –13.9% (0.7%). At 6 months, fasting insulin levels weresignificantly reduced from baseline in the intervention groups (allP<.01), whereas DHEAS and glucose levels were unchanged. Core bodytemperature was reduced in the calorie restriction and calorierestriction with exercise groups (both P<.05). After adjustment forchanges in body composition, sedentary 24-hour energy expenditure wasunchanged in controls, but decreased in the calorie restriction (–135kcal/d [42 kcal/d]), calorie restriction with exercise (–117 kcal/d[52 kcal/d]), and very low-calorie diet (–125 kcal/d [35 kcal/d])groups (all P<.008). These "metabolic adaptations" (~ 6% more thanexpected based on loss of metabolic mass) were statistically differentfrom controls (P<.05). Protein carbonyl concentrations were notchanged from baseline to month 6 in any group, whereas DNA damage wasalso reduced from baseline in all intervention groups (P <.005).Conclusions Our findings suggest that 2 biomarkers of longevity(fasting insulin level and body temperature) are decreased byprolonged calorie restriction in humans and support the theory thatmetabolic rate is reduced beyond the level expected from reducedmetabolic body mass. Studies of longer duration are required todetermine if calorie restriction attenuates the aging process in humans.Trial Registration ClinicalTrials.gov Identifier: NCT00099151Author Affiliations: Pennington Biomedical Research Center, LouisianaState University, Baton Rouge; and Garvan Institute for MedicalResearch, Darlinghurst, Australia (Dr Heilbronn).>> http://snipurl.com/ooxs> > Longevity researchers say they've shown for the first time that> following a strict low-calorie diet can decrease DNA damage linked> with aging.> > The findings are provocative, but preliminary. Longer-term research> will try to sort out whether such changes can meaningfully extend> people's lives, said senior author Ravussin of the Pennington> Biomedical Research Center at Louisiana State University.> > "They are the first proof that what has been observed in rodents seems> to be also working in humans," Ravussin said.> > The results are from the first phase of research at the Baton Rouge> center sponsored by a $12.4 million National Institute on Aging grant.> They follow unrelated research reported in January which suggested a> very restrictive diet seemed to help the heart age more slowly.> > The latest study appears in Wednesday's Journal of the American> Medical Association.>

[Guest guest]

Thanks very much, Dave,

I'm a little puzzled about the wording in the first: " reversal in two of three previously reported biomarkers of longevity (fasting insulin level and core body temperature)… ", though.

The second I guess clears it up.

But the main thing that puzzles me, is that obese people apparently experience a lower core temp also.

I'm back down to 98.2 deg today, having dropped the excess protein. I don't feel uncomfortably cold. I wonder if there's a magic level of say 98.0 (average of 97.4 and 98.6)that provides a compromise?

Just wondering - 97.4 is cold in the winter.

Regards.

[ ] Re: Severe calorie restriction reduces aging-related cell damage

Diane,I was just reading about this in another publication. Besidesreducing cell damage, CR also improved 2 other biomarkers:"Our results indicate that prolonged calorie restriction caused areversal in two of three previously reported biomarkers of longevity(fasting insulin level and core body temperature)… and a reduction inDNA fragmentation, reflecting less DNA damage," wrote lead authorLeonie Heilbronn from Louisiana State University.Another write-up on Nutraingredients.com, and the abstract from JAMAis copied below.Dave++++++++++++++++++http://www.nutraingredients.com/news/ng.asp?n=66877 & m=1NIE405 & c=lqeudkujayvvlpcCalorie-restricted diet could slow aging05/04/2006- Restricting your intake of calories may not only helppeople live longer, as well as losing weight, say the scientistsbehind a clinical trial.Previous studies have reported that calorie-restricted diets couldprolong the lives of rodents and other short-lived species, but, untilnow, no such human study has been undertaken to investigate theeffects of such diets on markers of human aging.The Comprehensive Assessment of the Long Term Effects of ReducingIntake of Energy (CALERIE) study, published in the new issue of theJournal of the American Medical Association (Vol. 295, pp. 1539-1548),followed 48 middle-aged, overweight, non-obese men and women eatingone of four calorie-controlled diets for six months.The participants (21 men, 27 women) were randomly assigned to eat oneof four diets: control (weight maintenance diet); calorie restriction(calorie intake reduced by 25 per cent of normal); calorie restrictionwith exercise (calorie intake reduced by 12.5 per cent, energyexpenditure increased by 12.5 per cent); very low-calorie diet (890kilocalories per day until 15 per cent weight loss and then weightmaintenance diet).After six months, the control group had a measured weight loss ofabout 1 per cent. The three intervention groups, as expected, lostsignificantly more weight. Both the calorie restriction and calorierestriction with exercise groups lost about 10 per cent during thetrial, while the low-calorie group lost on average 14 per cent, inkeeping with the design study.Weight loss was not the primary focus of the study however, andpositive results for the calorie restriction were observed for markersof aging."Our results indicate that prolonged calorie restriction caused areversal in two of three previously reported biomarkers of longevity(fasting insulin level and core body temperature)… and a reduction inDNA fragmentation, reflecting less DNA damage," wrote lead authorLeonie Heilbronn from Louisiana State University."We are the first to report a significant decline in DNA damagefollowing six months of calorie restriction in non-obese men andwomen," stressed Heilbronn.One of the most widely accepted theories on aging is that reactiveoxygen species (ROS) attack, amongst other things, DNA, affect normalcell function and lead to again and, potentially, the development ofcancer.No changes were recorded in other markers of longevity, includingdehydroepiandrosterone sulfate (DHEAS) levels, or in fasting glucoselevels, which have been measured in both primates and longer-livedmen, an inconsistency suggested to be due to the short duration of theCALERIE study.Interestingly, a `metabolic adaptation' (a change in the use ofenergy) was observed and occurred in the first three months of thetrial, with no further changes at the end of the trial."The metabolic adaptation in the calorie restriction with exercisegroup was similar to that observed in the calorie restriction group,suggesting that energy deficit rather than calorie restriction itselfis driving the decrease in energy expenditure," said Heilbronn.In an accompanying editorial, Luigi Fontana from Washington UniversitySchool of Medicine welcomed the study as adding a considerable amountof information to the current understanding of the subject."It is anticipated that the study by Heilbronn et al will stimulateadditional investigation of the effects of calorie restriction inhumans," said Fontana.Dr. Fontana called for longer-term studies with larger samplepopulations to measure changes to hormones, metabolism and geneexpression caused by such diets."Although it is not likely that many individuals would adopt acalorie-restricted diet, the value of these studies is that theysuggest possible mechanisms of aging in humans and points ofintervention to modify the effects of aging," concluded Fontana.The call for more study was echoed by Helen Stracey, a registereddietitian on behalf of the British Dietetic Association."It is true that calorie restriction increases longevity in rats, thishas been proved," Stracey told NutraIngredients.com."This study is in humans but unfortunately the sample size is toosmall (46 people counting the drop outs) for us to conclude anythingand in particular extrapolate anything to the general population. Theconclusion is that larger studies of longer duration are needed todetermine if calorie restriction attenuates the aging process."http://jama.ama-assn.org/cgi/content/abstract/295/13/1539?maxtoshow= & HITS=10 & hits=10 & RESULTFORMAT= & fulltext=calerie & searchid=1 & FIRSTINDEX=0 & resourcetype=HWCITEffect of 6-Month Calorie Restriction on Biomarkers of Longevity,Metabolic Adaptation, and Oxidative Stress in Overweight IndividualsA Randomized Controlled TrialLeonie K. Heilbronn, PhD; Lilian de Jonge, PhD; Madlyn I. Frisard,PhD; P. DeLany, PhD; D. Enette Larson-Meyer, PhD; Rood,PhD; Tuong Nguyen, BSE; Corby K. , PhD; Volaufova, PhD; M. Most, PhD; L. Greenway, PhD; R. , MD;Walter A. Deutsch, PhD; A. on, PhD; Ravussin, PhD;for the Pennington CALERIE TeamJAMA. 2006;295:1539-1548.Context Prolonged calorie restriction increases life span in rodents.Whether prolonged calorie restriction affects biomarkers of longevityor markers of oxidative stress, or reduces metabolic rate beyond thatexpected from reduced metabolic mass, has not been investigated in humans.Objective To examine the effects of 6 months of calorie restriction,with or without exercise, in overweight, nonobese (body mass index, 25to <30) men and women.Design, Setting, and Participants Randomized controlled trial ofhealthy, sedentary men and women (N = 48) conducted between March 2002and August 2004 at a research center in Baton Rouge, La.Intervention Participants were randomized to 1 of 4 groups for 6months: control (weight maintenance diet); calorie restriction (25%calorie restriction of baseline energy requirements); calorierestriction with exercise (12.5% calorie restriction plus 12.5%increase in energy expenditure by structured exercise); verylow-calorie diet (890 kcal/d until 15% weight reduction, followed by aweight maintenance diet).Main Outcome Measures Body composition; dehydroepiandrosteronesulfate (DHEAS), glucose, and insulin levels; protein carbonyls; DNAdamage; 24-hour energy expenditure; and core body temperature.Results Mean (SEM) weight change at 6 months in the 4 groups was asfollows: controls, –1.0% (1.1%); calorie restriction, –10.4% (0.9%);calorie restriction with exercise, –10.0% (0.8%); and very low-caloriediet, –13.9% (0.7%). At 6 months, fasting insulin levels weresignificantly reduced from baseline in the intervention groups (allP<.01), whereas DHEAS and glucose levels were unchanged. Core bodytemperature was reduced in the calorie restriction and calorierestriction with exercise groups (both P<.05). After adjustment forchanges in body composition, sedentary 24-hour energy expenditure wasunchanged in controls, but decreased in the calorie restriction (–135kcal/d [42 kcal/d]), calorie restriction with exercise (–117 kcal/d[52 kcal/d]), and very low-calorie diet (–125 kcal/d [35 kcal/d])groups (all P<.008). These "metabolic adaptations" (~ 6% more thanexpected based on loss of metabolic mass) were statistically differentfrom controls (P<.05). Protein carbonyl concentrations were notchanged from baseline to month 6 in any group, whereas DNA damage wasalso reduced from baseline in all intervention groups (P <.005).Conclusions Our findings suggest that 2 biomarkers of longevity(fasting insulin level and body temperature) are decreased byprolonged calorie restriction in humans and support the theory thatmetabolic rate is reduced beyond the level expected from reducedmetabolic body mass. Studies of longer duration are required todetermine if calorie restriction attenuates the aging process in humans.Trial Registration ClinicalTrials.gov Identifier: NCT00099151Author Affiliations: Pennington Biomedical Research Center, LouisianaState University, Baton Rouge; and Garvan Institute for MedicalResearch, Darlinghurst, Australia (Dr Heilbronn).>> http://snipurl.com/ooxs> > Longevity researchers say they've shown for the first time that> following a strict low-calorie diet can decrease DNA damage linked> with aging.> > The findings are provocative, but preliminary. Longer-term research> will try to sort out whether such changes can meaningfully extend> people's lives, said senior author Ravussin of the Pennington> Biomedical Research Center at Louisiana State University.> > "They are the first proof that what has been observed in rodents seems> to be also working in humans," Ravussin said.> > The results are from the first phase of research at the Baton Rouge> center sponsored by a $12.4 million National Institute on Aging grant.> They follow unrelated research reported in January which suggested a> very restrictive diet seemed to help the heart age more slowly.> > The latest study appears in Wednesday's Journal of the American> Medical Association.>