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Wednesday, September 19, 2012

Calorie restriction for longevity ~ For mice, not man

Work in any field long enough and you get a “nose” for the job. It is an instinctive reaction to some new event or idea, built on decades of the passive accumulation of knowledge in ones chosen field. I’ve acquired such a nose an did so quite early on. Instinctively, I could spot a good, original and potentially new area of interest among a forest of dross. Equally, I could sniff a no-hoper, a line of research rapidly going nowhere. I first heard a lecture on calorie restriction over 15 years ago, appropriately at a hotel affiliated to the Orlando Disney Park. Rats, whose energy intake was restricted to 15 - 25% of caloric intake, lived longer than rats given as much as they liked to eat of standard rat chow. I neither like nor dislike rats but it remains that I really have no feelings for them of any substance. The fact that the caloric restriction made them live longer was really of no interest to me, other than to wonder how rats feel about longevity in a captive and restricted, if not slave-like existence. However, translating this to humans really made me titter. We live in an extraordinarily obesogenic environment with overweight and obesity abounding and growing in prevalence to every corner of the globe and with quack diets and trash books for every desirable attribute, including weight loss and aging, dominating the mass media. So, it appears from the rat handlers, that  we are to think about adding caloric restriction as an additional string to our public health nutrition bow to beat the grim reaper and steal a few more mortal years. As one of my teachers used to say in exasperation in class at daft responses: “Ye gods and little fishes.”

The effect of caloric restriction on longevity was first reported in 1935 and has now been studied in yeast, worms, flies and rodents and a 15-15% restriction in energy intake in the latter can increase longevity by up to 60%. Such is the wealth of data on these  diverse species that one must accept the literature that caloric restriction prolongs life expectancy. The big question is the translation of that concept to man. Relative to these species, we mature far more slowly and have a longer life span. People often talk about human equivalents of “dog years” but in absolute terms, we outlive dogs by at least 8 fold.

The Calorie Restriction Society[1] boasts 7,000 members. One such member is described in a journalistic piece on the web site. This member is 48 years old, is fit as a fiddle, weighs 118 pounds which is 7 pounds less than the minimum recommended for his height, he confines his energy intake to 1,500 calories a day and although his energy expenditure is not described, he would appear to be very physically active. He first got interested in caloric restriction as a tool to longevity when he was faced with his first manifestation of aging, a receding hairline. Poor guy!!!

The whole are of calorie restriction took a hit recently when the National Institute on Aging published its long term study of energy restriction on longevity in rhesus monkeys, a species far closer to man than yeast, flies, worms and mice[2].   A 20 year study examined the effects of caloric restriction introduced to rhesus monkeys at varying stages of life. No statistically significant differences were observed between control monkeys fed ad libitum and those calorie-restricted (10-40% restriction). The latter did achieve a longer life span than would normally be expected for this species but the authors point out that they lived a privileged life of good husbandry and veterinary care. The main causes of death did not differ between the two groups:cancer, cardiovascular disease and general organ deterioration. However, generally recognised beneficial biomarkers of health increased in the caloric restricted monkeys but this did not translate into a longer life. In fairness to the literature, another colony of monkeys elsewhere (different diet, management and breeds)  did respond but in the world of science, it only takes one black swan to demolish a theory. The recent Nature paper is that black swan.

From a practical point of view, I can see a few dedicated enthusiasts sharing the necessary skills via social networks to achieve successful caloric restriction but I fail to see how it would be dealt with the great majority of the people. Leaving aside the ever-present obesogenic food supply, how is the average person to know exactly what their energy requirements are and then how to pare that down by 20% or more of that to achieve the required level of calorie restriction? How, especially with increasing age, do we ensure that caloric restriction does not drift into malnutrition which in the older population is so strongly associated with increased admission to hospitals, increased complications hen there, longer stays and more frequent re-admissions. Professor James Hill of the University of Colorado in his excellent book “The Step Diet” [3], recommends 25,000 steps per day plus rejection of 25% of the food served at every meal, just to maintain weight loss. For the many fatties among us, moi included, there is (a) the need to shed pounds to an appropriate avoirdupois a la James Hill and (b) having done so, to then hit a 25% calories restriction.
It ain’t going to happen. My nose was right!

Finally, apologies for the late post of this blog but that happens. Also next two mondays are in Asia and a lot of teaching at China Agricultural University in Beijing and Honk Kong University so I’ ll try but please be understanding!

[2] Mattison JA et al (2012) Nature, 489 (7415), 318-321

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