July 20, 2010

Late onset calorie restriction reduces cellular senescence, protects telomeres

Research presented at the British Society for Research on Ageing conference, held July 15-16 in Newcastle, England reveals that calorie restriction, even started later in life, reduces cellular senescence: the point at which at which a cell can no longer replicate, which has been hypothesized to be a major cause of aging due to its impact on the body's tissues.

Researchers at the Biotechnology and Biological Sciences Research Council Centre for Integrated Systems Biology of Ageing and Nutrition (CISBAN) at Newcastle University fed adult mice a calorie restricted diet for a short period of time beginning in adulthood and found a decrease of the accumulation of senescent cells in their livers and intestines, which normally accumulate high amounts of senescent cells with age. They also found that the animals' telomeres, which are protective caps on the ends of the chromosomes that prevent errors as DNA replicates, were better maintained and markers of cumulative oxidative tissue damage were reduced.

"Many people will have heard of the theory that eating a very low calorie diet can help to extend life span and there is a lot of evidence that this is true," lead researcher Chunfang Wang commented. "However, we need a better understanding of what is actually happening in an organism on a restricted diet. Our research, which looked at parts of the body that easily show biological signs of ageing, suggests that a restricted diet can help to reduce the amount of cell senescence occurring and can reduce damage to protective telomeres. In turn this prevents the accumulation of damaging tissue oxidation which would normally lead to age-related disease."

"It's particularly exciting that our experiments found this effect on age-related senescent cells and loss of telomeres, even when food restriction was applied to animals in later life," added Professor Thomas von Zglinicki, who contributed to the work. "This proof of principle encourages us at CISBAN in our search for interventions that might in the foreseeable future be used to combat frailty in old patients."

Calorie restriction

People imagine that caloric restriction is associated with near-starvation and constant hunger, or malnutrition due to inadequate intake of dietary nutrients. In fact, caloric restriction, if undertaken correctly, is a healthy lifestyle that is accompanied by weight loss, only occasional hunger, optimal nutrition, and other health benefits. To stress the importance of a healthy lifestyle, caloric restriction will henceforth be referred to as "caloric restriction with optimal nutrition" or CRON.

Practicing CRON means decreasing caloric intake by 30 percent to 40 percent while following the principles of a healthy diet and greatly limiting the consumption of calorie-dense, nutrient-poor foods such as white flour and refined sugar. It is also important that additional vitamins and minerals be added to any caloric restriction program to supply any missing nutrients. Only calories, not nutrients, should be limited (Nicolas AS et al 1999).

Researchers initially speculated that animals who consumed fewer calories would also expend less energy. However, careful measurements of the energy expenditures of animals on CRON indicate that they use as much or more energy than their free-feeding counterparts (Duffy PH et al 1991; Masoro EJ et al 1982; Masoro EJ et al 1992; McCarter RJ et al 1992).

In spite of the comparable energy expenditure, however, CRON reduces the cellular damage that is typically associated with higher energy expenditure, including accumulation of ROS products, lipid peroxidation, oxidized proteins, and other measures of cellular aging (Cook CI et al 1998; Dubey A et al 1996; Matsuo M et al 1993).

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