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Sunday, 20 April 2014

How to Live forever (or die trying)...

Although (with a BMI currently hovering around 32 and having only just resumed regular gym sessions) I'm hardly a poster-boy for healthy living, I've always been intrigued by the possibility of extending natural lifespan in humans via Calorie Restriction (CR). This is often termed CRAN (Calorie Restriction with Adequate Nutrition), CRON (Calorie Restriction with Optimal Nutrition), or CRL (Calorie Restriction for Longevity) in order to clearly differentiate it from eating disorders such as anorexia nervosa, where food intake is restricted, but in an unhealthy manner.

While there's no doubt that obesity can lead to numerous health issues and premature death, in practice it is often difficult to lose weight (and keep it off) and achieve the recommended BMI of around 22. Otherwise the developed countries wouldn't be experiencing an 'obesity epidemic'. Then, once you achieve a healthy BMI and take regular aerobic and strength training exercise, is the any further benefit to be achieved via CRAN?

While CRAN had been proven in multiple independent experiments to extend lifespan in simpler species (such as worms and mice), there was little hard data on the effects (for good or bad) that CRAN could have on humans. Most historical examples of calorie restriction were simply cases of starvation, where the adverse effects of malnutrition were the dominant factor. Given the ethical issues surrounding doing CRAN studies on randomly selected groups of human test subjects, the best scientific data applicable to humans is likely to come from primate studies (although there are a number of people voluntarily adopting CRAN to some degree as a lifestyle choice, such isolated cases are not a controlled study).

A study published a few years ago (by the NIA) had seemed to show that in rhesus monkeys CRAN had no significant beneficial effect. And yet a new study published only a few weeks ago (ref: Colman, R.J. et al. "Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys." Nat. Commin. 5:3557 doi: 10.1038/ncomms4556 (2014).) has found that CRAN did indeed have a significant effect on rhesus monkey survival rates. The apparent disparity in results is (according to the authors of the new study) due to the 'control' monkeys in the NIA study having not actually been fed 'ad libitum', but instead had, unintentionally, been fed on a slightly calorie-restricted diet (as shown by the fact that this 'control' group had lower average weights than is typical for Rhesus monkeys in captivity). The 'control' group had therefore already been getting some of the benefits available from CRAN (as shown by the unusually high survival rate to 40 years - the equivalent of around 116 years old for a human!).

As a very rough approximation of how effective CRAN 'might' be when applied to humans (from young adulthood - so this will be more relevant to DS1 and DS2 than myself!), I've scaled the age of Rhesus monkeys (by a factor of 2.9) to bring the survival rate curve of the monkey 'control' group (red squares) in line with that of UK humans in 2010 (blue diamonds). The scaled plot of the CRAN group of Rhesus monkeys (green triangles) should therefore be roughly in line with what one might expect to happen in the case of humans adopting a CRAN diet from young adulthood onwards.

Hopefully this could mean that instead of around 50% of humans in developed countries surviving to age 80, and very few making it past 100, by adopting a CRAN diet for their adult life, around 50% of people could live past 100, although the maximal natural lifespan could probably not stretch much past 130. The main benefit would be a significant reduction in the many disabling age-related illnesses that often reduce quality of life past 70.

It will be very interesting what happens to the surviving Rhesus monkeys over the next 5 or so years, but which time the survivors will be achieving the normal 'maximal lifespan'.

All in all, there seems to be sufficient evidence to warrant not only my getting down to my 'healthy weight' BMI of around 21-23 (and going to the gym 2-3 times a week), but for me (and later on my sons), adopting a modest level of CR (say 80% of 'normal' maintenance calorie intake) while ensuring our diet has no nutritional deficits. In practice this can be as simple as cutting out all 'empty calories' from snacks and junk foods, and avoiding (or at least minimising) processed foods that all generally high in fats, salt, and/or sugar.

The biggest hurdle is the self-control/psychological one associated with most forms of dietary restriction. If it was easy I would have stuck with CRAN since I first learned about it (and got down to my healthy BMI) back when I was in my mid thirties. I'm due to get my annual blood test done next week, and I'll post some selected biomarkers (BMI, cholesterol etc.) for the past couple of years and update them annually. Hopefully I'll be able to get down to a healthy weight again over the coming year, and transition into a more healthy CRAN-based dietary lifestyle. After all, there's not much point being wealthy if you're in poor health and die young!

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