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Tuesday, Oct 15, 2019

Scientists identify part of gene, longevity; to help design better drugs

The gene was first identified as the longevity gene in yeast two decades ago and was known to be activated by reduced dietary inputs

mumbai Updated: Apr 28, 2017 16:23 IST
Snehal Fernandes
Snehal Fernandes
Hindustan Times

Lifestyle diseases such as obesity, diabetes, Alzheimer’s, and heart diseases can now be treated effectively.

Scientists at Tata Institute of Fundamental Research (TIFR) have identified a region in a gene – called longevity gene – that could help pharmaceutical companies design better drugs that can provide targeted therapy.

The gene – Sirtuin1 (SIRT1) – was first identified as the longevity gene in yeast two decades ago. Known to be activated by reduced dietary inputs – commonly referred to as calorie restriction – the longevity gene has been hotly pursued as a therapeutic target against age-related and lifestyle diseases.

Pharmaceutical companies have for long contemplated designing a drug that activates and targets specific biological pathways to tackle lifestyle diseases. However, information on which region in the protein determines specific biological pathways or factors that it controls has been largely lacking, and therefore manufacturing a drug has been less fruitful, said researchers.

“Most often drugs fail because pathways that are undesirable are also activated. The region in the gene that we have identified is very important as it determines which specific biological pathway it can [or cannot] activate,” said Ullas Kolthur, lead investigator, and associate professor at the department of biological of sciences, TIFR. “This region determines the specificity of interaction with other proteins that will be useful in understanding how this gene protects against morbid diseases such as diabetes, obesity, neurodegenerative disorders and cardiovascular diseases.”

The study used mice as experimental models as they closely resemble humans in terms of genes, biology and behaviour traits.

“In the past two decades, research has indicated that targeting this gene is important because its gives protection against several diseases including neurodegeneration, obesity, diabetes, cardiovascular diseases,” said Kolthur. “So increased expression or better functioning of this gene/protein means the organism lives longer, and can cope better with stress.”

This gene makes a particular protein that is able to modulate and control the properties of several proteins inside all cells, making it a master regulator. However, this may be detrimental as it can activate even those biological pathways that could be counter-productive, if uncontrolled.

The team’s findings, said researchers, support recent literature, which has shown the currently available drug molecules are likely to be targeting the same region without being aware of it. “We have shown that this region in SIRT1 is not only important for binding to a drug but is also important for determining its specificity towards cellular factors,” said Prof. Kolthur.

The team also identified a variant of this gene that does not have this region, and future work will investigate its importance and functions.

First Published: Apr 28, 2017 16:22 IST

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