Action Potential

Another way for the sirtuins to enhance longevity

ResearchBlogging.org

What do obesity and Parkinson’s disease have in common? Strains on our current health care system? Well…yes, but apparently another answer is the sirtuin family of deacetylases. A new study published in Science claims that controlling the activity of sirtuin2 (SIRT2) can be neuroprotective against alpha-synuclein pathology.

The sirtuins are better known for their influence on aging, with many studies demonstrating an increase in the lifespan of several different organisms if these genes are activated. One way to turn on these genes is by stressing an organism, for example through caloric restriction, leading to the activation of SIRT1. SIRT1 can also be directly activated by Resveratrol. Mice that overexpress SIRT1 exhibit several properties associated with a restricted diet, and increased longevity, including low cholesterol, low blood glucose, and low insulin levels. Interestingly, increased SIRT1 expression and/or activity delays the Parkinson’s pathology associated with aggregating alpha-synuclein.

SIRT2, another sirtuin family member, is mainly expressed in the brain and is known to be involved with cell cycle regulation, however, the variety of substrates that have been identified for this deacetylase (including tubulin, histones and p53) suggests that it may serve in several cellular capacities. A group at Harvard decided to reduce the expression of SIRT2 through RNAi or small molecule inhibitors, and found that, unlike SIRT1, reduced expression and activity of SIRT2 protected against neuronal cell death in culture and even in a Drosophila model of Parkinson’s. Although not completely confirmed, one possibility for the differences discovered regarding the activity levels and neuroprotection between the different sirtuin isoforms is that SIRT1 and SIRT2 act in opposing manners when influencing signaling pathways, with each deacetylase providing checks and balances against the other’s actions.

It is exciting that we are beginning to gain an understanding of the signaling systems that influence aging, with the sirtuins exhibiting a knack for extending lifespan, including the maintenance of good health through our digestive systems, and apparently now in our brains. I suspect that we can expect much more from sirtuin research.

Outeiro, T., Kontopoulos, E., Altmann, S., Kufareva, I., Strathearn, K., Amore, A., Volk, C., Maxwell, M., Rochet, J., McLean, P., Young, A., Abagyan, R., Feany, M., Hyman, B., & Kazantsev, A. (2007). Sirtuin 2 Inhibitors Rescue -Synuclein-Mediated Toxicity in Models of Parkinson’s Disease Science, 317 (5837), 516-519 DOI: 10.1126/science.1143780

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    michael said:

    The main reasons I can see that causes shorter lives is smoking, and oxidation within our diet.