Another example of calorie restriction slowing a specific aspect of the damage of aging: "restricting the caloric intake of adult female mice prevents a spectrum of abnormalities, such as extra or missing copies of chromosomes, which arise more frequently in egg cells of aging female mammals. ... We found that we could completely prevent, in a mouse model, essentially every aspect of the declining egg quality typical of older females. We also identified a gene that can be manipulated to reproduce the effects of dietary caloric restriction and improve egg quality in aging animals fed a normal diet, which gives us clues that we may be able to alter this highly regulated process with compounds now being developed to mimic the effects of caloric restriction. ... The long-term effects of a caloric restriction (CR) diet in humans are being investigated in ongoing studies, but some health improvements, including reductions in cholesterol levels and other cardiovascular risk factors, have already been reported. ... While the mechanisms by which caloric restriction produces its effects are still being investigated, several of the metabolic pathways involve a regulator of DNA transcription called PGC-1a, which is known to modulate genes involved in controlling mitochondrial number and function. [The researchers] also found that egg cells from female mice lacking a functional PGC-1a gene who were allowed to free feed through adulthood maintained the same egg-cell quality as seen in the CR mice. However, combining CR with PGC-1a inactivation did not increase the effects beyond those achieved separately, which suggests that the two approaches work in a common pathway."