Human Calorie Restriction Studies Continue Apace

Studies of the biochemistry of calorie restriction (CR) in humans are being held in a number of research institutes in the US. So far, as expected, the beneficial biochemical changes caused by CR in humans look very much like the biochemical changes observed in mice, rats, and rhesus monkeys. That bodes well for a gain in human life span as a result of this practice, though at the present level of available biotechnology there is little option but to wait and see what the results will be on that count. The consensus amongst biogerontologists appears to be that CR will extend human life span by a handful of percentage points, but practitioners of calorie restriction would be expected to evade or resist all of the common age-related diseases.

Biologist Michael Rose, known for his work on aging in flies, is a calorie restriction (CR) skeptic, it would seem. He and John Phelan have developed a mathematical model that predicts a "lifetime of low-calorie dieting would only extend human life span by about 7 percent, unlike smaller animals, whose life spans are affected more by the effects of starvation. ... Longevity is not a trait that exists in isolation; it evolves as part of a complex life history, with a wide range of underpinning physiological mechanisms involving, among other things, chronic disease processes."

Bear in mind that estimates for the expected difference in human life span between people who exercise regularly and people who do not exercise regularly are in the range of 10 years, give or take a few years. There is no medical technology available today that can achieve anywhere near these sorts of results.

In any case, you might look at this recent paper which examines CR in healthy, thin people:

Calorie restriction (CR) slows aging and is thought to improve insulin sensitivity in laboratory animals. In contrast, decreased insulin signaling and/or mild insulin resistance paradoxically extends maximal lifespan in various genetic animal models of longevity. Nothing is known regarding the long-term effects of CR on glucose tolerance and insulin action in lean healthy humans.

In this study we evaluated body composition, glucose, and insulin responses to an oral glucose tolerance test and serum adipokines levels in 28 volunteers, who had been eating a CR diet for an average of 6.9 +/- 5.5 years, (mean age 53.0 +/- 11 years), in 28 age-, sex-, and body fat-matched endurance runners (EX), and 28 age- and sex-matched sedentary controls eating Western diets (WD).

We found that the CR and EX volunteers were significantly leaner than the WD volunteers. Insulin sensitivity [was] significantly higher in the CR and EX groups than in the WD group (P = 0.001). Nonetheless, despite high serum adiponectin and low inflammation, approximately 40% of CR individuals exhibited an exaggerated hyperglycemic response to a glucose load. This impaired glucose tolerance is associated with lower circulating levels of IGF-1, total testosterone, and triiodothyronine, which are typical adaptations to life-extending CR in rodents.

As for other human studies of CR, it shows that the CR metabolism is better set up for long term health and avoidance of age-related disease.

ResearchBlogging.orgFontana L, Klein S, & Holloszy JO (2009). Effects of long-term calorie restriction and endurance exercise on glucose tolerance, insulin action, and adipokine production. Age (Dordrecht, Netherlands) PMID: 19904628

Comments

It's always the same problem: quantity versus quality.

Starving to get a few more years of life seems a good alternative to the typical USAmerican junk food diet. But maybe not for those who live to enjoy the delights of 3 stars stars like Adriá, Arzak, Berasategui, etc.

Posted by: El Guerrero del Interfaz at November 17th, 2009 6:40 AM

Did he say ONLY 7 percent ?

As in, ONLY 4 years ?

Posted by: jay at November 17th, 2009 1:01 PM

@jay: that's in the context of the same degree of calorie restriction producing 30-40% extension of life in mice.

But yes, people seem willing to jump through all sorts of hoops in aim of adding a few years to their life. A pity that so many ignore exercise and CR as options, given that those are the only presently working options for basically healthy people. Everything else (and especially that portion of everything else touted by the "anti-aging" marketplace) is a mirage, but there are always plenty of people willing to buy a mirage that promises gain without working for it.

Posted by: Reason at November 17th, 2009 1:15 PM

Below is a recent email to William H. Millard, founder of the Millard Foundation, and supporter of Aubrey de Grey. The email is self-explanatory, and suggests that the approach to regenerative medicine taken by de Grey, with its disregard of metabolism, is doomed to continued inconsequence; and that the resolution of the problem is not one that can be helped by money, but is instead a question of science. Getting the science right turns out to be not a matter of basic research, or advanced research, but an escape from preconceptions about metabolism.

Mr. William Millard,
Having witnessed your video "Regenerative Medicine: Why and When?," and upon hearing your invitation at its finish to contact you if I wanted to help advance the first regenerative protocol, I wrote the following letter.
First I would like to say that all of the approaches to regeneration of aging bodies or amelioration of age-related decrepitude discussed in the video are unrealistically expensive even if they should be made feasible, and this makes them elitist and irrelevant to the people of the world.  Secondly, none of them is anything more than an ad hoc, stop-gap measure introduced at a time in life when the cascade of systemic problems starts to become a torrent.  Too much sand in the hour glass has rundown.
Thirdly, and most importantly, I want to direct your attention to the presentation of Aubrey de Grey.  De Grey claims at one and the same time that there is still a lot of ignorance about the nature of metabolism, and that it is the corrosive part of metabolism that causes the pathology whose accumulation shows up as the deterioration of aging.  De Grey is only correct about the first part.  That ignorance shows up in the second part.  The deterioration is a result of too little metabolism, which in and of itself is not at all corrosive.  The problem occurs with de Grey's understanding of metabolism in particular, and with the opacity of the concept in the life sciences in general.
Neither de Grey nor life scientists are adequately informed of the nature of chemical energy.  The study of metabolism began as consideration of heat retention and loss.  And although metabolic measurement has advanced to quantification of sugar and oxygen consumption in vitro, in vivo measurement too is limited to measurement of these things in moments of equilibrium, that is, when the patient is at rest and not having had eaten for 12 or more hours prior to measurements.  Those making the measurements in both cases can neither handle deviations from equilibrium, nor can they determine how much of either (oxygen or sugar) went to heat production.  In fact the inclusion of thermogenesis as part of metabolism removes any consideration of efficiency when caloric expenditure is calibrated.
This shortcoming is no more starkly demonstrated than in the field of mathematical biology, where a power law called Kleiber's Law is used to describe the relation between metabolic rate and body mass.  The most common and recent handling of the equation is that termed quarter power scaling.  The major proponents of this version of the law (West, Enquist, Savage, Brown, etc.) suggest that within it are held perhaps the secret to aging.  Data from metabolic energy measurement across hundreds of species do not support the relevance of the equation.  The eponymous Max Kleiber arrived at the equation in the early 30's upon consideration of heat generation of an assortment of species.  The term for metabolic rate is in calories/sec.  As I said above, techniques of measurement have changed, though thermogenesis is still considered part of metabolism.
In a recently published paper of mine, "The terrestrial evolution of metabolism and life - by the numbers" (Theoretical Biology and Medical Modelling, an on-line journal) the term for efficiency was introduced, where efficiency was measured against loss to heat.  Thermogenesis was ruled out as a metabolic consideration except to the extent that it affected the term for efficiency.  Efficiency was a redox coupling ratio of amperes to amperes.  Metabolic rate was expressed in watts.  Unlike the standard approach to metabolism presumed by quarter power scaling, in which efficiency is assumed to be 100%, an approach that rules out thermogenesis as part of metabolism suggests efficiency is lower than 35% for most creatures.
Thermogenesis was not a consideration in the origins of life at submarine volcanic vents.  Thermogenesis is not a consideration for phytoplankton multiplying on the submerged surface of antarctic icebergs.  What is important in both cases is the generation of the covalent bonds of organic molecules necessary for growth and reproduction.  Consider now the predominant metaphor of the cell as a battery.  The understanding of life's origins, and its longevity, must be viewed in these terms, where the battery is an organic battery.  Metabolic rate becomes recharge rate.  In the paper mentioned above, Kleiber's Law is considered in these terms.  These terms deal solely with the essentials of life: water, energy, organic molecules, and salt.  The organic molecules, and their aggregations, expressed in grams, are then considered in terms of their electrical properties, expressed in the term metabolic efficiency.
What the paper then deals with is an examination of the morphogenetic influences of the thermodynamic pressures for equilibrium, given fluctuations in energy availability, and in the electrical properties of the biomass that capture and expend that energy in growth and replication.  And it is in the graph and table of numbers for this equation [Metabolic rate = grams biomass (4x efficiency - 1)/4x efficiency] that the secrets to the aging process and the energetic nature of all biological organization can be plumbed.  The equation models the effects of caloric restriction on longevity.  It models the energetic conditions present at the start of life at submarine volcanic vents, and how life had to change to survive and flourish on the ascent to the surface.
The paper deals with these issues.  In the conclusion are presented some inferences based upon the math and the idea the same forces and pressures there at the start of life, are still what drives it and determines its phases today.  These inferences deal with the use of battery discharge into the body to alter the exponent of biomass so that metabolic recharge rate increases, thereby increasing the endurance of the organic battery that is a human being.  The numbers behind the inference suggest fit human life span can be extended easily.  The key inference is muscle cell mass can be maintained and increased through this discharge, overcoming debilitation from disuse following prolonged bed-rest, stroke, concussion, immobilization, and the degeneration of aging.  It is cheap.  It is easy.  It is here now.  And there is historical evidence supporting this claim.  In this regard I direct you to the essay on electrotherapy at https://en.wikipedia.org/wiki/User:Gregory_O%27Kelly/Sandbox .
I have already attempted several times over the years to interest Aubrey de Grey in this.  The man, being a traditionally trained geneticist (as you can see in his presentation in your video) is ignorant of the details of metabolism.  And, no doubt, he is ignorant of the physics of batteries and covalent bonds.  Yet I am sure he, or you, have people who are capable of understanding the mathematics.  Currently I am awaiting peer review upon a follow-up paper, "Parsing the numbers - lessons from the allometric scaling of metabolism," that goes into a more involved mathematical analysis, pointing out the relevance of the numbers for a variety of things from weight regain after dieting, to mutation, fermentation, and the relation between food and reproduction for creatures large and small.  And how, again, battery discharge into the body can aid in weight loss, prevent mutation, and restore the integrity and functionability of somatic and nervous structures.
I encourage you to investigate the first paper at the site for Theoretical Biology and Medical Modelling.  Hidden within it is the justification for the investigation of a regenerative and revivifying protocol that is here today, and available even for the poor and downtrodden.

Posted by: Gregory O'Kelly at November 19th, 2009 5:09 PM

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