Fasting and calorie restriction
It is obvious that living to the maximum (well beyond 100 years) is no longer just a whim but rather a cooperative effort: one pursued by committed individuals as well as scientists. It is reassuring to know that individuals can actively contribute to their odds of living long and living well (through mind-set, diet, supplements, and exercise) and that the scientific community is just as passionate about helping them achieve their objective.
Since genes control every aspect of biological life (including health, senescence, and longevity) and caloric restriction extends healthy life span, a rational approach to finding biomarkers of aging is to compare gene expression in normal aging animals with gene expression in calorie-restricted animals (a heretofore slow, labor intensive, and costly pursuit).
A tremendous breakthrough occurred when scientists at the University of Wisconsin used high-density DNA microarrays (gene chips), a technology developed by Affymetrix (Santa Clara, California) to rapidly detect expression in up to 6,347 genes at one time. When researchers (Richard Weindruch and Tomas Prolla) compared gene activity in normally aging mice with gene expression in calorie-restricted mice, they found that many of the genetic changes of aging were reversible by calorie restriction (Lee et al. 1999).
Recently, scientists have shown that a single gene can control both life span and the timing of systemic and cellular aging in mammals, indicating only a few pivotal genes may be intricately involved in longevity.
For example, unlike calorie-restricted mice, long-lived Snell dwarf mice ate all they wanted, became obese and exhibited higher levels of leptin (a hormone derived from fat tissue). Researchers are aware that the Pit1 gene produces dwarfism in Snell dwarf mice as a result of impairments in the pituitary, the master gland. These impairments result in deficiencies of three hormones: thyroid hormone, growth hormone, and prolactin. Thus, it appears that the life extension mechanism may rely on deficiencies of one or more of these hormones. Some researchers believe that a deficiency in the growth hormone may be the most interesting of the three in explaining longevity (recall that insulin-like growth factor-1 (IGF-1) is made in response to growth hormone) (Premo 2001; Kent 2003).
When the exact genes that govern aging are pinpointed, scientists will be able to target those genes, the proteins they produce and the biologic mechanisms they affect in order to develop new drugs and other therapies to slow aging, prevent disease, and extend healthy life span.