Life Extension Update
|April 12, 2004|
|Life Extension Update Exclusive |
World’s oldest living mouse celebrates fourth birthday
The average lifespan of laboratory mice is a little over two years. But unlike laboratory mice whose lifespans were extended by months of calorie restriction, birthday mouse Yoda owes his longevity to good genes.
Professor of pathology at the University of Michigan (U-M) Geriatrics School, Richard A Miller, MD PhD developed several strains of mice from wild mice captured Idaho. The strains developed by Dr Miller stay smaller, age more slowly and live longer than wild mice. Yoda’s parents were members of a strain of mutant dwarf mice developed at Jackson Laboratories. Although some calorie restricted mice may have survived even longer than Yoda, he is the oldest mouse alive today that Dr Miller knows of. The mice are providing information concerning how genes affect the rate of human aging and late-life disease risk. Dr Miller’s current work, published in the December 2003 issue of the European Journal of Immunology, identifies T cell defects in older mice that adversely affect immune response.
Dr Miller commented, “Yoda is only the second mouse I know to have made it to his fourth birthday without the rigors of a severe calorie-restricted diet. He's the oldest mouse we've seen in 14 years of research on aged mice at U-M. The previous record-holder in our colony died nine days short of his fourth birthday. Hundred-year-old people are much more common than four-year-old mice.”
Yoda is currently living in a “rest home” for geriatric mice that belongs to Dr Miller, and shares his quarters with a larger mouse named Princess Leia.
Fasting and calorie restriction
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.
Aging causes irreversible damage to the body's proteins. The underlying mechanism behind this damage is glycation. A simple definition of glycation is the cross-linking of proteins and sugars to form nonfunctioning structures in the body. The process of glycation can be superficially seen as wrinkled skin. Glycation is also an underlying cause of age-related catastrophes including the neurologic, vascular, and eye disorders. Carnosine is a unique dipeptide that interferes with the glycation process. When compared to the anti-glycating drug aminoguanidine, carnosine has been shown to inhibit glycation earlier in the process and also provides additive health benefits.
Findings from published scientific literature indicates that resveratrol may be the most effective plant extract for maintaining optimal health.
Red wine contains resveratrol, but the quantity varies depending on where the grapes are grown, the time of harvest, and other factors. After more than two years of research, a standardized resveratrol extract is now available as a dietary supplement. This whole grape extract contains a spectrum of polyphenols that are naturally contained in red wine such as proanthocyandins, anthocyanins, flavonoids, etc.
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