Does CR really lower metabolism?

[Guest guest]

In several studies and discussions, the idea that lower metabolism

leads to longer lifespans has been called into question, as some of

you may know already. It seems that CR does not lower energy

expenditure to the degree (theoretically?)expected by cutting certain

given percentages of daily calories but there has been " the recent

suggestion that under some circumstances (CR?)we might expect

mitochondria to produce fewer free radicals when metabolism is

higher--particularly when they are uncoupled " .

1: Mech Ageing Dev. 2005 Jun-Jul;126(6-7):783-93. Epub 2005 Mar 16.

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Energy expenditure of calorically restricted rats is higher than

predicted from their altered body composition.

Selman C, T, Staib JL, Duncan JS, Leeuwenburgh C,

Speakman JR.

University of Florida, Department of Aging and Geriatric Research,

College of Medicine, Gainesville, 32608, USA. c.selman@...

Debate exists over the impact of caloric restriction (CR) on the

level of energy expenditure. At the whole animal level, CR decreases

metabolic rates but in parallel body mass also declines. The question

arises whether the reduction in metabolism is greater, smaller or not

different from the expectation based on body mass change alone.

Answers to this question depend on how metabolic rate is normalized

and it has recently been suggested that this issue can only be

resolved through detailed morphological investigation. Added to this

issue is the problem of how appropriate the resting energy expenditure

is to characterize metabolic events relating to aging phenomena. We

measured the daily energy demands of young and old rats under ad

libitum (AD) food intake or 40% CR, using the doubly labeled water

(DLW) method and made detailed morphological examination of

individuals, including 21 different body components. Whole body energy

demands of CR rats were lower than AD rats, but the extent of this

difference was much less than expected from the degree of caloric

restriction, consistent with other studies using the DLW method on CR

animals. Using multiple regression and multivariate data reduction

methods we built two empirical predictive models of the association

between daily energy demands and body composition using the ad lib

animals. We then predicted the expected energy expenditures of the CR

animals based on their altered morphology and compared these

predictions to the observed daily energy demands. Independent of how

we constructed the prediction, young and old rats under CR expended 30

and 50% more energy, respectively, than the prediction from their

altered body composition. This effect is consistent with recent

intra-specific observations of positive associations between energy

metabolism and lifespan and theoretical ideas about mechanisms

underpinning the relationship between oxygen consumption and reactive

oxygen species production in mitochondria.

PMID: 15888333 [PubMed - indexed for MEDLINE]

I'm sure the following has already been discussed here. I wonder how

much light is shed upon its principal hypothesis as a result of the

above abstract.

1: Aging Cell. 2004 Jun;3(3):87-95.

Uncoupled and surviving: individual mice with high metabolism have

greater mitochondrial uncoupling and live longer.

Speakman JR, Talbot DA, Selman C, Snart S, McLaren JS, Redman P,

Krol E, DM, MS, Brand MD.

Aberdeen Centre for Energy Regulation and Obesity (ACERO), School

of Biological Sciences, University of Aberdeen, Aberdeen, Scotland, UK

AB24 2TZ. j.Speakman@...

Two theories of how energy metabolism should be associated with

longevity, both mediated via free-radical production, make completely

contrary predictions. The 'rate of living-free-radical theory' (Pearl,

1928; Harman, 1956; Sohal, 2002) suggests a negative association, the

'uncoupling to survive' hypothesis (Brand, 2000) suggests the

correlation should be positive. Existing empirical data on this issue

is contradictory and extremely confused (Rubner, 1908; Yan & Sohal,

2000; Ragland & Sohal, 1975; Daan et al., 1996; Wolf & Schmid-Hempel,

1989]. We sought associations between longevity and individual

variations in energy metabolism in a cohort of outbred mice. We found

a positive association between metabolic intensity (kJ daily food

assimilation expressed as g/body mass) and lifespan, but no

relationships of lifespan to body mass, fat mass or lean body mass.

Mice in the upper quartile of metabolic intensities had greater

resting oxygen consumption by 17% and lived 36% longer than mice in

the lowest intensity quartile. Mitochondria isolated from the skeletal

muscle of mice in the upper quartile had higher proton conductance

than mitochondria from mice from the lowest quartile. The higher

conductance was caused by higher levels of endogenous activators of

proton leak through the adenine nucleotide translocase and uncoupling

protein-3. Individuals with high metabolism were therefore more

uncoupled, had greater resting and total daily energy expenditures and

survived longest - supporting the 'uncoupling to survive' hypothesis.

Copyright 2004 Blackwell Publishing Ltd.

PMID: 15153176 [PubMed - indexed for MEDLINE]