5.2.2 Calorie restriction
Since the publication of Osborne, Mendel and Ferry's paper (Science, 1917, Vol 45, pp. 294–5) calorie restriction has been the most reliable method of extending the lifespan of laboratory animals. These results have been confirmed by many researchers and have been extended to a variety of vertebrate and invertebrate animals. The mechanisms underlying this effect of calorie restriction are not clear, because calorie restriction affects different systems in different ways. For example:
it delays or even prevents the onset of age-related loss of crystalline protein in lens tissue
it reduces the number of fat cells
it impairs the ability to maintain the normal oestrous cycle.
In addition to these changes, calorie restriction seems to modulate metabolic processes and make them more efficient than in control animals fed ad libitum. More importantly, calorie-restricted animals maintain a higher efficiency of enzyme regulation as they age. They also show reduced levels of advanced glycation end products and free radicals. It appears that the production of free radicals, mitochondrial defects and glycation of proteins are closely interrelated processes, which play crucial roles in cellular ageing, and are modulated by calorie restriction. Therefore, many research laboratories have focused their attention on the role of oxidative damage, age-dependent DNA changes, mitochondrial function and protein glycation in calorie-restricted animals during ageing.