Further Explorations in Calorie Restriction

Once money starts flowing into a field, as it has been for the study of the longevity and health benefits of calorie restriction in the past couple of years, you'll find a contingent working on advancing knowledge by mapping those parts of the problem space not yet paved and built up. I thought I'd point out a couple of recent papers that take a short term study approach by examining the effects of calorie restriction of different dietary components on mitochondrial metabolism. Given the link between mitochondrial free radical generation, cellular damage and degenerative aging, this might be a helpful proxy for effects on long term health and longevity.

Carbohydrate restriction does not change mitochondrial free radical generation and oxidative DNA damage:

Many previous investigations have consistently reported that caloric restriction (40%), which increases maximum longevity, decreases mitochondrial reactive species (ROS) generation and oxidative damage to mitochondrial DNA (mtDNA) in laboratory rodents. These decreases take place in rat liver after only seven weeks of caloric restriction. Moreover, it has been found that seven weeks of 40% protein restriction, independently of caloric restriction, also decrease these two parameters, whereas they are not changed after seven weeks of 40% lipid restriction. This is interesting since it is known that protein restriction can extend longevity in rodents, whereas lipid restriction does not have such effect. However, before concluding that the ameliorating effects of caloric restriction on mitochondrial oxidative stress are due to restriction in protein intake, studies on the third energetic component of the diet, carbohydrates, are needed.

Not all dietary components are equal - some are a good deal more equal than others, it seems. Research into protein restriction has been going on for a while, but there's no such thing as too much supporting evidence. This next study heads off in the other direction, however, in search of benefits obtained without restricting protein:

Synergistic effects of caloric restriction with maintained protein intake on skeletal muscle performance in 21-month-old rats: a mitochondria-mediated pathway:

Caloric restriction (CR) delays the onset of age-related mitochondrial abnormalities but does not prevent the decline in ATP production needed to sustain muscle protein fractional synthesis rate (FSR) and contractile activity. We hypothesized that improving mitochondrial activity and FSR using a CR diet with maintained protein intakes could enhance myofibrillar protein FSR and consequently improve muscle strength in aging rats. Wistar rats (21 months old) were fed either an ad libitum (AL), 40% protein-energy restricted (PER) or 40% AL-isonitrogenous energy restricted (ER) diet for 5 months.


the synergistic effects of CR with maintained protein intake may help to limit the progression of sarcopenia by optimizing the turnover rates and functions of major proteins in skeletal muscle.

People like optimizing complex things - such as metabolic processes that contribute to longevity and health. Enjoyment of this sort of activity is hardwired into us; a very necessary part of our success story as individuals and as a species. Long after aging has been defeated through the application of advanced technology, there will be communities that optimize baseline human metabolism for fun.

But today, it's something of a distraction - there are better initiatives we could be advancing with these resources, so as to more rapidly and effectively defeat aging. You can't get to the finish line by manipulating metabolism; all you can do is buy a little more time. But if you spent all your efforts on that, what time is left to really work on the defeat of aging?

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This is your argument over and over. People
are wasting their time b/c they are not working
on what you think is best.

The reality is way more complex than you suggest.
CR study will lead to understanding of the genes
involved in longevity. This may lead to understanding of repair mechanisms for Mi-DNA,
which gets back to the type of research you prefer. In other words, they're not distinct.

Then there's the fact that the delay of a decade
is not really a decade of lost time. What will
be able to be accomplished 10 years from now
per unit of time will be dramatically increased
from today.

It's not as simple as you're boiling it down to.
And it's not a waste of time either.

Posted by: Joel at December 9th, 2006 5:58 AM

I'm not suggesting that any of this is a waste of time. I'm suggesting it's too slow and low-yield in comparison to other methods. It's a utility argument.

On a timescale of a couple of decades, as I've argued in the past, you can't benefit greatly from accelerating change in research capabilities. The human processes of funding and organization - and thus the business cycles of commercialization - are incompressible below a certain level while people are still people.

Ten years spend working on X followed by 10 years working on Y is most certainly not going to lead to result Y twenty years from now, if result Y requires twenty years of work now. The science component of that work is somewhat small compared to the regulatory and commercial side.

Many millions will suffer and die unnecessarily over the next few decades if we are complacent about steering research into the most effective way forward.

Posted by: Reason at December 9th, 2006 10:44 AM

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