Baton Rouge: Scientists are nearer to creating an anti-ageing pill after discovering why eating less can help mankind live longer.
Studies in a number of animals, from worms to mice and monkeys, have oncluded that if you eat enough nutrients to be healthy but cut calories to the minimum, perhaps to half the normal daily amount – that lifespan could be extended by up to half, pushing well over a century, while cutting the risk of cancer, heart disease, and strokes.
Now a study published in PLoS Medicine, gives more information into how calorie restriction translates into a longer life is published by a team that has studied what happens in the body during these extreme diets. It is thought the effects could be mimicked with a ”long life” pill.
The reserachers at the Pennington Biomedical Research Centre in Baton Rouge, Lousiana, studied a key factor in the age-related decline of bodily functions – the accumulation of “oxidative damage” in the body’s proteins, fats, and DNA.
Oxidants – in particular, damaging chemical intermediates called “free radicals” – are produced when food is converted to energy by cellular structures called mitochondria.
One theory on how calorie restriction slows ageing is that it lowers free-radical production by inducing the formation of efficient mitochondria.
As oxidative damage has been linked to ageing, this could explain how limiting calorie intake without malnutrition extends life span, say the researchers
The team studied 36 healthy overweight but non-obese young people. A third of them received 100 per cent of their energy requirements in their diet; the calorie restriction group had their calorie intake reduced by 25 per cent; and the calorie restriction plus exercise group had their calorie intake reduced by 12.5 per cent and their energy expenditure increased by 12.5 per cent.
The researchers found that a 25 per cent calorie deficit for six months decreased the overall calories burned by the body, which suggests improved function of mitochondria, the “batteries” in cells.
The researchers also examined the way genes winked on and off in the participants. In yeast, worms, and flies the activation of one particular gene, called Sir2, increases life span and regulates cellular metabolism. An important question is whether caloric restriction can regulate affect the human equivalent, called SIRT1.
Civitarese and colleagues found that fewer calories did indeed increase the use of SIRT1 in muscle, suggesting SIRT1 may contribute to more efficient metabolism, less oxidative stress, and increase longevity in humans too.
Intriguingly, the protein is activated by a compound found in red wine, called resveratrol, which has been linked by earlier research with extended life span in yeast and in tiny worms called nematodes. Sirtuins are the subject of research around the world, said Dr Civitarese, because they offer the hope of extending lifespan and possibly suggesting treatments for metabolic diseases such as diabetes and neurological disorders such Alzheimer’s and Huntington’s diseases.
Exercise and dieting to improve the function of mitochondria remain the first action that doctors recommend to diabetics but it now seems that resveratrol, acting via SIRT1, can also boost mitochondrial function too.
Prof Johan Auwerx at the University Louis Pasteur in Strasbourg, with Sirtris Pharmaceuticals in Cambridge, Massachusetts, has shown in a study of 120 Finnish volunteers that a variant of SIRT1 is linked to accelerated metabolism.
Sirtris has finished two phase 1 human safety studies with SRT501, an improved formulation of resveratrol that is capable of producing levels in human volunteers comparable to those used in the animal studies – native resveratrol can not reach therapeutic levels- to do this, you would need to drink 100s of glasses of red wine or take 100s of pills of nutraceutical products — per day. Sirtris has now started a phase 1b study in 90 patients with diabetes with STT501.