Harvard Medical School researcher David Sinclair may be on the verge of discovering the legendary elixir of youth—this time in the form of resveratrol, a molecule found in red wine. The idea may seem fantastical, but the biochemical mechanisms behind aging and its prevention are now clearer than ever. In particular, the Sinclair lab has shown that resveratrol and other diverse allosteric activators associated with anti-aging functions work through a common pathway via regulation of the SIRT1 deacetylase.
Sinclair’s lab focuses on longevity pathways and their relation to disease, and the lab’s work is at the forefront of the aging field. In 2003, the lab discovered resveratrol, a molecule that, when injected into mice, slowed aging and provided other physiological benefits similar to those associated with dieting and exercise. Since then, the lab has been probing the mechanism behind resveratrol and other similar molecules’ effect on longevity in order to better understand aging overall.
Aging occurs, in part, as a result of the protein SIRT1, an enzyme that deacetylates certain proteins, an imperative step in the cellular regulation and longevity processes. This enzyme, which is part of a family of aging-related proteins called sirtuins, is activated when bound by a molecule such as resveratrol. Activation is linked to a single amino acid in SIRT1, namely glutamate-230 in the N-terminal domain of the enzyme. Knowledge of this specific site could enhance the outcomes of further drug discovery and development associated with anti-aging.
With such a discovery, Sinclair says, “The impact would be global.”
This SIRT1 regulation pathway is not unique to resveratrol. In fact, there is now a whole family of synthetically manufactured drugs called STACs, or synthetic sirtuin-activating compounds, which mimic resveratrol in both their mechanisms and their effects. These synthetic molecules are much more potent than their naturally occurring resveratrol counterpart, leading to the possibility of future drugs that can reduce aging significantly in humans. With such a discovery, Sinclair says, “The impact would be global, both economically and socially.”
Now, more so than ever before, researchers are finding direct links between aging and other physiological functions. For example, the enzyme SIRT1 is directly affected by dieting and exercise, for its activity increases as a result of those behaviors and shuts off in their absence, a phenomenon accompanying obesity. Additionally, the mechanisms accompanying aging correlate strongly to those associated with memory loss, for resveratrol and STACs, the same molecules that accompany anti-aging, affect memory loss prevention as well through.
The implications of these relationships abound. In addition to slowing down aging, these molecules also affect a wide range of other diseases, from neurodegeneration to inflammatory bowel disease to Type II diabetes. Sinclair says, “In the future, we could create medicines to treat one disease that would simultaneously protect against other diseases associated with aging.”
For centuries, people have looked for means to combat aging and the diseases associated with it. “The difference today,” Sinclair says, “is that now we have the technology to make a successful attempt at it.”
Lily Zhang is a Brevia staff writer. She can be reached at firstname.lastname@example.org. Featured image credit: Los Angeles Times