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Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates
Published on: February 27, 2016
Small molecule SIRT1 activators for the treatment of aging and age-related diseases
Basil P Hubbard1, David A Sinclair2
1Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Abstract:
Recent studies in mice have identified single molecules that can delay multiple diseases of aging and extend lifespan. In theory, such molecules could prevent dozens of diseases simultaneously, potentially extending healthy years of life. In this review, we discuss recent advances, controversies, opportunities, and challenges surrounding the development of SIRT1 activators, molecules with the potential to delay aging and age-related diseases. Sirtuins comprise a family of NAD⁺-dependent deacylases that are central to the body's response to diet and exercise. New studies indicate that both natural and synthetic sirtuin activating compounds (STACs) work via a common allosteric mechanism to stimulate sirtuin activity, thereby conferring broad health benefits in rodents, primates, and possibly humans. The fact that two-thirds of people in the USA who consume multiple dietary supplements consume resveratrol, a SIRT1 activator, underscores the importance of understanding the biochemical mechanism, physiological effects, and safety of STACs.
Insights
Single molecules, known as SIRT1 activators, show promise in delaying aging and extending lifespan by activating sirtuin enzymes. Further research is crucial to understand their full potential and safety for human health.
Area of Science:
- Biochemistry
- Gerontology
- Molecular Biology
Background:
- Sirtuins are NAD+-dependent deacylases crucial for cellular responses to diet and exercise.
- Single molecules have been identified that can delay aging and extend lifespan in preclinical studies.
- SIRT1 activators (STACs) are compounds that stimulate sirtuin activity, offering potential health benefits.
Purpose of the Study:
- To review recent advances in the development of SIRT1 activators.
- To discuss controversies, opportunities, and challenges in the field.
- To explore the mechanism, effects, and safety of STACs.
Main Methods:
- Review of recent scientific literature on SIRT1 activators.
- Analysis of studies in rodents, primates, and humans.
- Discussion of the allosteric mechanism of STACs.
Main Results:
- SIRT1 activators confer broad health benefits in various species.
- Natural and synthetic STACs share a common allosteric mechanism.
- Resveratrol, a known SIRT1 activator, is widely consumed as a supplement.
Conclusions:
- SIRT1 activators hold significant potential for delaying aging and age-related diseases.
- Understanding the mechanism and safety of STACs is critical for therapeutic development.
- Further research is needed to translate these findings to human health benefits.
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