Metabolic Slowing and Reduced Oxidative Damage with Sustained Caloric Restriction Support the Rate of Living and Oxidati

[Todd Allen]

It looks to me like modest results from a modest intervention.

 

http://www.cell.com/cell-metabolism/fulltext/S1550-4131(18)30130-X

 

Summary

Calorie restriction (CR) is a dietary intervention with potential benefits for healthspan improvement and lifespan extension. In 53 (34 CR and 19 control) non-obese adults, we tested the hypothesis that energy expenditure (EE) and its endocrine mediators are reduced with a CR diet over 2 years. Approximately 15% CR was achieved over 2 years, resulting in an average 8.7 kg weight loss, whereas controls gained 1.8 kg. In the CR group, EE measured over 24 hr or during sleep was approximately 80–120 kcal/day lower than expected on the basis of weight loss, indicating sustained metabolic adaptation over 2 years. This metabolic adaptation was accompanied by significantly reduced thyroid axis activity and reactive oxygen species (F2-isoprostane) production. Findings from this 2-year CR trial in healthy, non-obese humans provide new evidence of persistent metabolic slowing accompanied by reduced oxidative stress, which supports the rate of living and oxidative damage theories of mammalian aging.

 

[mccoy]

Todd, you say the results are mdoest but the subjects were young people and 15% calorie-restricted.

 

At the end, there is a metabolic slowdown which, over the decades, might cumulatively give the system a longevity advantage (providing the theory of rate of living is right).

 

Of course, should the restriction bring about the known immunitary and other problems, over the decades the advantage would be compensated by these drawbacks.

[Todd Allen]

I probably could have worded my disclaimer better.  This is a result from one of the bigger/longer studies of CR in people and one might wish it had a lot to say about the value of CR for life extension.  But I doubt anyone here will find much to get excited about in the study or the results.

 

The CR cohort started at 34.2 ± 6.6 % body fat and over 2 years lost −5.6 ± 0.3 % bodyfat with ~15% CR and they averaged about 100 kCal/day of reduced energy expenditure beyond that expected for lost body mass and a reduction of one measure of oxidative stress.  This suggests some benefit for slightly obese people who got a little under the obesity threshhold of body fat.  I don't think this study supports in any significant way the idea pursued here of quite thin/lean people following much stricter CR for life seeking longevity exceeding normal expectations.

[mccoy]

This suggests some benefit for slightly obese people who got a little under the obesity threshhold of body fat.  I don't think this study supports in any significant way the idea pursued here of quite thin/lean people following much stricter CR for life seeking longevity exceeding normal expectations.

 

Todd  as a whole I agree, except for the fact that maybe we should call the partecipants overweight, since I believe the conventional threshold for obesity is BMI=30 kg m^-2. 

 

The interesting bottomline is maybe that the results seem to support the following theories:

• Rate of living (Metabolic rate or EE)
• Oxydative stress - free radicals (maybe, since this has not been shown to decreas in centenary Okinawans and otehr studies)

That is, CR seems to decrease both EE and Oxydative stress, as rigorously measured during the trial.

 

The article seems to be pretty objective, underlining its limitations. There are also some interesting comments at the end (Mediators of Energy Metabolism, Biomarkers of Aging, and Relationship with Metabolic Adaptation).

 

Interesting to remark, the Rate of living and oxydative stress theories are supported by some staunch promoters of the low-carb diet such as Ron Rosedale. They support a low-carb, low-protein, hi fat diet as a CR mimetics, with the purpose to lower metabolic rate and oxydative stress.

 

Of course, decreasing both protein and glucose will drastically decrease leucine signalling and IGF-1 signalling hence downregulate mTOR, which is arguably at the base of the benefits of CR. 

The only drawback being the possible excess of fats. 

[Sibiriak]

Mccoy: maybe we should call the participants overweight...

 

 

Many were not overweight (defined as 25.0 to <28.0 kg/m2 in the study): 

 

 

all subjects were healthy with 22 (41.5%) being normal weight and 31 (58.5%) slightly overweight at screening.

 

 

Terminology aside, I agree that Todd's basic point is still valid (" I don't think this study supports in any significant way the idea pursued here of quite thin/lean people following much stricter CR for life seeking longevity exceeding normal expectations.")

[Todd Allen]

The only advantage of using BMI to classify obesity is that it is super easy to measure.  Otherwise it considers body builders obese and makes people like me with muscle wasting think they are healthy at very harmful levels of body fat.

 

From the wikipedia page on obesity.

>Body fat percentage is total body fat expressed as a percentage of total body weight. There is no generally accepted definition of obesity based on total body fat. Most researchers have used >25% in men, and >30% in women, as cut-points to define obesity.

 

If the above is accurate then my calling this mixed male and female cohort starting at an average of 34.2% bodyfat slightly obese is on target.  I also saw the statement in the paper describing the participants as normal weight or slightly overweight but think under muscled would have been a better description given how fat they were by dexa scan.

 

As for the assumption that lowered oxidative stress through CR is a desirable outcome here is a paper which I think provides interesting discussion both for and against this idea.

http://journals.sagepub.com/doi/pdf/10.2203/dose-response.13-035.Ristow

[mccoy]

I agree that BMI is used as a proxy for adiposity but often it is not a good proxy. If adiposity has been measured by Dexa scans, then it should govern of course.

The average BMI in the study was 25-26 kgm-2, so on the average the subjects were overweight, whereas there sure were people with less than 25 BMI due to statistical variability, reported in the study as +- standard deviation I believe.

Conversely, if we choose bodyfat to define obesity, and we decide that the threshold is 30, then on the average those people, with 33-34% fat, were obese. Whereas some were not, because of statistical variability.

 

I'm interested into the article on ROS, although I'll take my time to read it all. ROS as signaling molecules is a specific line of research as we've already discussed and the hormetic effect is another beneficial mechanism.

the Okinawans centenaries display an higher concentration of antioxidant molecules, so maybe the deleterious side effect of peroxydes signaling is coutneracted by the beneficial presence of abundant antioxydants as described in the article. But I just browsed the article on ROS.