To live long – fast, eat right and sleep

“The best of all medicines are rest and fasting,” said the well known American statesman, writer Benjamin Franklin, while Mahatma Gandhi used fasting as an effective political tool against the British during the freedom movement as well as maintain his lifestyle.

However, the exact benefits of dietary restrictions or fasting on the human health system have not been scientifically well understood.

Now, a scientific team, including Nooruddin Khan from the University of Hyderabad and Bali Pulendran of US have found a mechanism by which the body’s system is able to adapt to nutrient scarcity and explain the benefits of diet restrictions.

The scientists have identified a gene-GCN2 (General controlled non-repressedkinase), which is a metabolic sensor involved in amino acid (building blocks of protein) starvation. The activation of this gene is the key that helps in boosting a vaccine induced immunity. They tumbled upon this mechanism while studying immune responses to the yellow fever vaccine (known to be among the most effective vaccines).

The research pointed out that low protein diet or Caloric Restriction can help boost immunity. Explaining the role of the gene, Nooruddin told BusinessLine that it can sense a starvation like condition in the stomach and gets activated. It starts cleaning up the system (autophagy) by getting rid of unwanted proteins and organic substances, which in turn raise the immunity and suppress the inflammation process in the gut.

Restricting amino acids without leading to a malnutrition condition will dramatically bolster vaccine-induced immunity and protection of intestinal inflammation in the stomach. In simple words dietary restrictions or a balanced diet can protect us from a variety of disorders, especially inflammatory types and extend lifespan.

Of vaccines, drugs and applications

The scientists suggest that vaccine additives, called adjuvants that are effective in stimulating the gene and regulate a response to starvation within cells would be potent in stimulating long-lasting immunity. They have been using this knowledge to engineer vaccines against infections like Dengue, TB and HIV.

The researchers are identifying molecules (plant based derivates) than can activate or mimic the gene function. In addition, they are trying to use them as adjuvants and blend them with existing vaccines to improve their efficacy, said Nooruddin.

In a research paper published in the March 16 issue of Nature, Pulendran and Khan have shown that a low protein diet or drugs that mimic its effect on immune cells, could be tools for the treatment of inflammatory bowel diseases such as Crohn’s disease or Ulcerative colitis.

In Mice fed with a low protein diet (2 per cent, compared to 16 per cent in standard diet) or a diet lacking only the amino acid leucine, were protected from signs of Colitis, such as weight loss and bloody diarrhoea. On the other hand Mice lacking the GCN2 gene were not protected from colitis when fed a low protein diet, which demonstrated the protective role of the gene.

Implications for pharma industry

The researchers interpret the findings to have implications for the treatment of inflammatory bowel diseases and auto-immune diseases such as rheumatoid arthritis and psoriasis. For the pharma industry, this understanding could open up avenues of developing drugs.

At the UoH, Nooruddin’s team is probing the biology of nutrient sensing and immunological regulations in infections diseases like TB, Dengue and HIV. Simultaneously they are developing new mimetics and nano-based delivery systems which can mimic similar conditions and can be used as adjuvants in novel vaccine development as well as therapeutic interventions against metabolic diseases such as Diabetes and IBDs.

Credits The Hindu Business Line

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