AsianScientist (Apr. 10, 2017) – Researchers from the Tata Institute of Fundamental Research (TIFR) have identified how the ‘longevity gene’ sirtuin 1 (SIRT1) is controlled. These findings, published in Cell Reports, could aid efforts aimed at designing specific pharmacological agents to activate the gene.
Since it was first identified two decades ago, SIRT1 has come to be associated with a protective role in diseases such as diabetes, obesity, neurodegeneration, atherosclerosis, autoimmune diseases, nephropathy and other conditions. Functionally, SIRT1 is known to be activated by reduced dietary inputs, commonly referred to as calorie restriction, and has been hotly pursued as a therapeutic target against age-related diseases.
Researchers at TIFR and other institutions have previously shown that SIRT1 increases longevity and reduces the risk of several diseases. However, efforts to develop therapies to activate this gene have been less fruitful for lack of clarity on the biochemical properties that provide specificity of function in different organs.
In this context, researchers led by Dr. Ullas Kolthur at TIFR Mumbai have identified a particular region of SIRT1 that can determine the specificity of interaction with other cellular regulators. Interestingly, the same region has also been implicated in binding several pharmacological agents that activate its functions.
The current findings clearly demonstrate the importance of a small region within the protein that determines the functional outcome by allowing SIRT1 to choose factors that it would interact with. Importantly, this region seems to be excluded in a variant of this gene, which is selectively expressed in organs such as brain and testes.
The researchers claim that these findings will enhance efforts at tackling several morbid non-communicable lifestyle diseases that plague modern humans and provide a new facet to our understanding of this longevity factor.
The article can be found at: Deota et al. (2017) Identification of a Tissue-Restricted Isoform of SIRT1 Defines a Regulatory Domain that Encodes Specificity.
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Source: Tata Institute of Fundamental Research.
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