This video segment adapted from NOVA scienceNOW examines the link between genes and diet and why certain people live longer than others. While mutations in specific genes seem to provide some groups of people with built-in protection against age-related disorders such as diabetes and heart disease, the amount of food one eats may also promote longevity by triggering a family of genes called sirtuins into action. Researchers are looking to develop drugs that will ward off disease and thereby promote longer life.
All cells have mechanisms by which certain genes are turned on or off when they are subjected to environmental stresses such as extreme cold, radiation, or viral attack. The genes respond to the stresses by producing proteins. But those mechanisms are prone to break down, especially as the body ages, often leading to serious disease. For nearly 70 years, scientists have known that one kind of stress, calorie restriction, actually prolongs life. In everything from single-celled yeast to worms, mice, and monkeys, persistent hunger has been shown to extend lifespan by as much as one-third. Scientists are currently studying what drives longevity on the molecular level and developing drugs designed to slow the aging process.
Longevity research is being conducted in many different areas. However, a common focus emerging in recent years is a family of genes called sirtuins. These genes may be responsible for the life-extending effects that have been associated with calorie restriction. Sirtuins have been highly conserved in evolution, meaning that they are found in very simple organisms such as yeasts and worms as well as mammals. In yeast cells, a protein called Sir2 attaches to repeating DNA sequences, which stabilizes the DNA. In addition, Sir2 can also repair damaged DNA. With younger cells, damage is typically limited. But as cells age, damage accumulates. The repair process cannot keep up, and the cell ultimately stops reproducing.
In recent years, Sir2 counterparts in more complex organisms have also been linked to stress response. Seven sirtuin genes have been identified in mammals. The genes reside in different parts of a cell and in different parts of the body. While evidence links their presence (or absence) to aging, the mechanisms that control their activities are not entirely understood. According to one study, sirtuins guard against cell death. When cells experience certain kinds of stress, such as calorie restriction, sirtuins stimulate protein and enzyme production, which in turn activates mitochondria to generate more energy. This slows down the cell's aging process significantly.
Another study is looking at resveratrol, a beneficial chemical found in red wine. High levels of resveratrol in the body are associated with high levels of protective sirtuins, suggesting that resveratrol stimulates sirtuin production. When cell protection fails, proteins misfold and fail to function. As inactive proteins accumulate, the system falls apart. Therefore boosting sirtuin levels in the body using resveratrol or some other chemical may help prevent—or at least slow the progression of—certain diseases, such as neurodegenerative diseases that involve misfolded proteins.
In sirtuins, scientists may have uncovered a universal mechanism for aging. As scientific understanding improves, drugs may one day be developed whereby small molecules manipulate sirtuins to control age-related diseases, including various cancers, adult-onset diabetes, and neurodegenerative diseases such as Alzheimer's and Parkinson's. Sirtuins research in its many variations demonstrates how advanced biomedical research and techniques may help resolve fundamental biological questions in ways that were hard to imagine, let alone achieve, just a few years ago.
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