Re: Severe calorie restriction reduces aging-related cell damage

[Guest guest]

Diane,

I was just reading about this in another publication. Besides

reducing cell damage, CR also improved 2 other biomarkers:

" Our results indicate that prolonged calorie restriction caused a

reversal in two of three previously reported biomarkers of longevity

(fasting insulin level and core body temperature)… and a reduction in

DNA fragmentation, reflecting less DNA damage, " wrote lead author

Leonie Heilbronn from Louisiana State University.

Another write-up on Nutraingredients.com, and the abstract from JAMA

is copied below.

Dave

++++++++++++++++++

http://www.nutraingredients.com/news/ng.asp?n=66877 & m=1NIE405 & c=lqeudkujayvvlpc

Calorie-restricted diet could slow aging

05/04/2006- Restricting your intake of calories may not only help

people live longer, as well as losing weight, say the scientists

behind a clinical trial.

Previous studies have reported that calorie-restricted diets could

prolong the lives of rodents and other short-lived species, but, until

now, no such human study has been undertaken to investigate the

effects of such diets on markers of human aging.

The Comprehensive Assessment of the Long Term Effects of Reducing

Intake of Energy (CALERIE) study, published in the new issue of the

Journal of the American Medical Association (Vol. 295, pp. 1539-1548),

followed 48 middle-aged, overweight, non-obese men and women eating

one of four calorie-controlled diets for six months.

The participants (21 men, 27 women) were randomly assigned to eat one

of four diets: control (weight maintenance diet); calorie restriction

(calorie intake reduced by 25 per cent of normal); calorie restriction

with exercise (calorie intake reduced by 12.5 per cent, energy

expenditure increased by 12.5 per cent); very low-calorie diet (890

kilocalories per day until 15 per cent weight loss and then weight

maintenance diet).

After six months, the control group had a measured weight loss of

about 1 per cent. The three intervention groups, as expected, lost

significantly more weight. Both the calorie restriction and calorie

restriction with exercise groups lost about 10 per cent during the

trial, while the low-calorie group lost on average 14 per cent, in

keeping with the design study.

Weight loss was not the primary focus of the study however, and

positive results for the calorie restriction were observed for markers

of aging.

" Our results indicate that prolonged calorie restriction caused a

reversal in two of three previously reported biomarkers of longevity

(fasting insulin level and core body temperature)… and a reduction in

DNA fragmentation, reflecting less DNA damage, " wrote lead author

Leonie Heilbronn from Louisiana State University.

" We are the first to report a significant decline in DNA damage

following six months of calorie restriction in non-obese men and

women, " stressed Heilbronn.

One of the most widely accepted theories on aging is that reactive

oxygen species (ROS) attack, amongst other things, DNA, affect normal

cell function and lead to again and, potentially, the development of

cancer.

No changes were recorded in other markers of longevity, including

dehydroepiandrosterone sulfate (DHEAS) levels, or in fasting glucose

levels, which have been measured in both primates and longer-lived

men, an inconsistency suggested to be due to the short duration of the

CALERIE study.

Interestingly, a `metabolic adaptation' (a change in the use of

energy) was observed and occurred in the first three months of the

trial, with no further changes at the end of the trial.

" The metabolic adaptation in the calorie restriction with exercise

group was similar to that observed in the calorie restriction group,

suggesting that energy deficit rather than calorie restriction itself

is driving the decrease in energy expenditure, " said Heilbronn.

In an accompanying editorial, Luigi Fontana from Washington University

School of Medicine welcomed the study as adding a considerable amount

of information to the current understanding of the subject.

" It is anticipated that the study by Heilbronn et al will stimulate

additional investigation of the effects of calorie restriction in

humans, " said Fontana.

Dr. Fontana called for longer-term studies with larger sample

populations to measure changes to hormones, metabolism and gene

expression caused by such diets.

" Although it is not likely that many individuals would adopt a

calorie-restricted diet, the value of these studies is that they

suggest possible mechanisms of aging in humans and points of

intervention to modify the effects of aging, " concluded Fontana.

The call for more study was echoed by Helen Stracey, a registered

dietitian on behalf of the British Dietetic Association.

" It is true that calorie restriction increases longevity in rats, this

has been proved, " Stracey told NutraIngredients.com.

" This study is in humans but unfortunately the sample size is too

small (46 people counting the drop outs) for us to conclude anything

and in particular extrapolate anything to the general population. The

conclusion is that larger studies of longer duration are needed to

determine if calorie restriction attenuates the aging process. "

http://jama.ama-assn.org/cgi/content/abstract/295/13/1539?maxtoshow= & HITS=10 & hit\

s=10 & RESULTFORMAT= & fulltext=calerie & searchid=1 & FIRSTINDEX=0 & resourcetype=HWCIT

Effect of 6-Month Calorie Restriction on Biomarkers of Longevity,

Metabolic Adaptation, and Oxidative Stress in Overweight Individuals

A Randomized Controlled Trial

Leonie 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 Team

JAMA. 2006;295:1539-1548.

Context Prolonged calorie restriction increases life span in rodents.

Whether prolonged calorie restriction affects biomarkers of longevity

or markers of oxidative stress, or reduces metabolic rate beyond that

expected 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, 25

to <30) men and women.

Design, Setting, and Participants Randomized controlled trial of

healthy, sedentary men and women (N = 48) conducted between March 2002

and August 2004 at a research center in Baton Rouge, La.

Intervention Participants were randomized to 1 of 4 groups for 6

months: control (weight maintenance diet); calorie restriction (25%

calorie restriction of baseline energy requirements); calorie

restriction with exercise (12.5% calorie restriction plus 12.5%

increase in energy expenditure by structured exercise); very

low-calorie diet (890 kcal/d until 15% weight reduction, followed by a

weight maintenance diet).

Main Outcome Measures Body composition; dehydroepiandrosterone

sulfate (DHEAS), glucose, and insulin levels; protein carbonyls; DNA

damage; 24-hour energy expenditure; and core body temperature.

Results Mean (SEM) weight change at 6 months in the 4 groups was as

follows: controls, –1.0% (1.1%); calorie restriction, –10.4% (0.9%);

calorie restriction with exercise, –10.0% (0.8%); and very low-calorie

diet, –13.9% (0.7%). At 6 months, fasting insulin levels were

significantly reduced from baseline in the intervention groups (all

P<.01), whereas DHEAS and glucose levels were unchanged. Core body

temperature was reduced in the calorie restriction and calorie

restriction with exercise groups (both P<.05). After adjustment for

changes in body composition, sedentary 24-hour energy expenditure was

unchanged in controls, but decreased in the calorie restriction (–135

kcal/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 than

expected based on loss of metabolic mass) were statistically different

from controls (P<.05). Protein carbonyl concentrations were not

changed from baseline to month 6 in any group, whereas DNA damage was

also 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 by

prolonged calorie restriction in humans and support the theory that

metabolic rate is reduced beyond the level expected from reduced

metabolic body mass. Studies of longer duration are required to

determine if calorie restriction attenuates the aging process in humans.

Trial Registration ClinicalTrials.gov Identifier: NCT00099151

Author Affiliations: Pennington Biomedical Research Center, Louisiana

State University, Baton Rouge; and Garvan Institute for Medical

Research, 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]

Diane,

I was just reading about this in another publication. Besides

reducing cell damage, CR also improved 2 other biomarkers:

" Our results indicate that prolonged calorie restriction caused a

reversal in two of three previously reported biomarkers of longevity

(fasting insulin level and core body temperature)… and a reduction in

DNA fragmentation, reflecting less DNA damage, " wrote lead author

Leonie Heilbronn from Louisiana State University.

Another write-up on Nutraingredients.com, and the abstract from JAMA

is copied below.

Dave

++++++++++++++++++

http://www.nutraingredients.com/news/ng.asp?n=66877 & m=1NIE405 & c=lqeudkujayvvlpc

Calorie-restricted diet could slow aging

05/04/2006- Restricting your intake of calories may not only help

people live longer, as well as losing weight, say the scientists

behind a clinical trial.

Previous studies have reported that calorie-restricted diets could

prolong the lives of rodents and other short-lived species, but, until

now, no such human study has been undertaken to investigate the

effects of such diets on markers of human aging.

The Comprehensive Assessment of the Long Term Effects of Reducing

Intake of Energy (CALERIE) study, published in the new issue of the

Journal of the American Medical Association (Vol. 295, pp. 1539-1548),

followed 48 middle-aged, overweight, non-obese men and women eating

one of four calorie-controlled diets for six months.

The participants (21 men, 27 women) were randomly assigned to eat one

of four diets: control (weight maintenance diet); calorie restriction

(calorie intake reduced by 25 per cent of normal); calorie restriction

with exercise (calorie intake reduced by 12.5 per cent, energy

expenditure increased by 12.5 per cent); very low-calorie diet (890

kilocalories per day until 15 per cent weight loss and then weight

maintenance diet).

After six months, the control group had a measured weight loss of

about 1 per cent. The three intervention groups, as expected, lost

significantly more weight. Both the calorie restriction and calorie

restriction with exercise groups lost about 10 per cent during the

trial, while the low-calorie group lost on average 14 per cent, in

keeping with the design study.

Weight loss was not the primary focus of the study however, and

positive results for the calorie restriction were observed for markers

of aging.

" Our results indicate that prolonged calorie restriction caused a

reversal in two of three previously reported biomarkers of longevity

(fasting insulin level and core body temperature)… and a reduction in

DNA fragmentation, reflecting less DNA damage, " wrote lead author

Leonie Heilbronn from Louisiana State University.

" We are the first to report a significant decline in DNA damage

following six months of calorie restriction in non-obese men and

women, " stressed Heilbronn.

One of the most widely accepted theories on aging is that reactive

oxygen species (ROS) attack, amongst other things, DNA, affect normal

cell function and lead to again and, potentially, the development of

cancer.

No changes were recorded in other markers of longevity, including

dehydroepiandrosterone sulfate (DHEAS) levels, or in fasting glucose

levels, which have been measured in both primates and longer-lived

men, an inconsistency suggested to be due to the short duration of the

CALERIE study.

Interestingly, a `metabolic adaptation' (a change in the use of

energy) was observed and occurred in the first three months of the

trial, with no further changes at the end of the trial.

" The metabolic adaptation in the calorie restriction with exercise

group was similar to that observed in the calorie restriction group,

suggesting that energy deficit rather than calorie restriction itself

is driving the decrease in energy expenditure, " said Heilbronn.

In an accompanying editorial, Luigi Fontana from Washington University

School of Medicine welcomed the study as adding a considerable amount

of information to the current understanding of the subject.

" It is anticipated that the study by Heilbronn et al will stimulate

additional investigation of the effects of calorie restriction in

humans, " said Fontana.

Dr. Fontana called for longer-term studies with larger sample

populations to measure changes to hormones, metabolism and gene

expression caused by such diets.

" Although it is not likely that many individuals would adopt a

calorie-restricted diet, the value of these studies is that they

suggest possible mechanisms of aging in humans and points of

intervention to modify the effects of aging, " concluded Fontana.

The call for more study was echoed by Helen Stracey, a registered

dietitian on behalf of the British Dietetic Association.

" It is true that calorie restriction increases longevity in rats, this

has been proved, " Stracey told NutraIngredients.com.

" This study is in humans but unfortunately the sample size is too

small (46 people counting the drop outs) for us to conclude anything

and in particular extrapolate anything to the general population. The

conclusion is that larger studies of longer duration are needed to

determine if calorie restriction attenuates the aging process. "

http://jama.ama-assn.org/cgi/content/abstract/295/13/1539?maxtoshow= & HITS=10 & hit\

s=10 & RESULTFORMAT= & fulltext=calerie & searchid=1 & FIRSTINDEX=0 & resourcetype=HWCIT

Effect of 6-Month Calorie Restriction on Biomarkers of Longevity,

Metabolic Adaptation, and Oxidative Stress in Overweight Individuals

A Randomized Controlled Trial

Leonie 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 Team

JAMA. 2006;295:1539-1548.

Context Prolonged calorie restriction increases life span in rodents.

Whether prolonged calorie restriction affects biomarkers of longevity

or markers of oxidative stress, or reduces metabolic rate beyond that

expected 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, 25

to <30) men and women.

Design, Setting, and Participants Randomized controlled trial of

healthy, sedentary men and women (N = 48) conducted between March 2002

and August 2004 at a research center in Baton Rouge, La.

Intervention Participants were randomized to 1 of 4 groups for 6

months: control (weight maintenance diet); calorie restriction (25%

calorie restriction of baseline energy requirements); calorie

restriction with exercise (12.5% calorie restriction plus 12.5%

increase in energy expenditure by structured exercise); very

low-calorie diet (890 kcal/d until 15% weight reduction, followed by a

weight maintenance diet).

Main Outcome Measures Body composition; dehydroepiandrosterone

sulfate (DHEAS), glucose, and insulin levels; protein carbonyls; DNA

damage; 24-hour energy expenditure; and core body temperature.

Results Mean (SEM) weight change at 6 months in the 4 groups was as

follows: controls, –1.0% (1.1%); calorie restriction, –10.4% (0.9%);

calorie restriction with exercise, –10.0% (0.8%); and very low-calorie

diet, –13.9% (0.7%). At 6 months, fasting insulin levels were

significantly reduced from baseline in the intervention groups (all

P<.01), whereas DHEAS and glucose levels were unchanged. Core body

temperature was reduced in the calorie restriction and calorie

restriction with exercise groups (both P<.05). After adjustment for

changes in body composition, sedentary 24-hour energy expenditure was

unchanged in controls, but decreased in the calorie restriction (–135

kcal/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 than

expected based on loss of metabolic mass) were statistically different

from controls (P<.05). Protein carbonyl concentrations were not

changed from baseline to month 6 in any group, whereas DNA damage was

also 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 by

prolonged calorie restriction in humans and support the theory that

metabolic rate is reduced beyond the level expected from reduced

metabolic body mass. Studies of longer duration are required to

determine if calorie restriction attenuates the aging process in humans.

Trial Registration ClinicalTrials.gov Identifier: NCT00099151

Author Affiliations: Pennington Biomedical Research Center, Louisiana

State University, Baton Rouge; and Garvan Institute for Medical

Research, 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.

>