A key protein in Drosophila, or can extend life by 20%

A key protein in Drosophila, or can extend life by 20%

January 31, 2018 Source: Biological Exploration of: Flora

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Regarding longevity, many genes or proteins have been listed on the shortlist and become star factors. Now, scientists have discovered a key protein that can bring health and longevity - Sirt4. More importantly, this protein is associated with “starvation metabolism” and is expected to become a new target for solving diseases such as diabetes and obesity.

Image source: Network

In the latest issue of the PNAS journal, scientists from Brown University have recently discovered that when the expression of Sirt4 protein in Drosophila is inhibited, its lifespan is shortened. Conversely, once the Sirt4 protein is upregulated, the lifespan of the fruit fly can be extended.

More importantly, the lack of Sirt4 protein increases the sensitivity of fruit flies to hunger, reduces their fertility and activity, and the inability to call energy stored in the body. This means that the enhancement of Sirt4 protein activity is expected to be an important way to treat age-related metabolic diseases, such as diabetes and obesity, resulting in healthy longevity.

"Research shows that Sirt4 protein is a key substance regulating the lifespan and metabolism of the body, especially the metabolic response to cope with hunger." Jason Wood, Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, said, "We are Once confirmed, Sirt4 protein overexpression can extend the lifespan of fruit flies."

Image source: PNAS (doi.org/10.1073/pnas.1720673115)

1. Extend 20% of healthy life

Initially, Sirt4 was found in mitochondria and belongs to a class of proteins called sirtuins. Studies have shown that sirtuins are associated with longevity, metabolism, genomic stability, diabetes, and neurodegeneration.

There are 7 different sirtuins proteins in human cells, 3 of which are located in mitochondria (Sirt3, Sirt4 and Sirt5). Only one sirtuins protein, Sirt 4, is expressed in Drosophila.

The author of the article, Stephen Helfand, a professor of biology at Brown University, led the team to find that when Sirt4 is overexpressed, the healthy lifespan of mutant flies is extended by 20%. Conversely, if the expression of Sirt4 is inhibited, the lifetime is reduced by 20%.

At the same time, if the cells do not express Sirt4 protein, even if nutrients and fat are stored in the body, fruit flies (without additional food) will die quickly. The researchers speculate that the biological changes brought about by changing the expression level of Sirt 4 may be equally applicable to humans.

This is Sirt4 (in green) in mitochondria (in red) of cells, with asuperimposed image on right (overlap in yellow).

(Source: Brown University)

2 , related to metabolism

Studies have also shown that Sirt 4 may be a gene responsible for fasting, especially when it comes from the conversion of carbohydrates to fat. In the case of malnutrition, the lack of the Sirt 4 gene accelerates death because the body does not have access to stored fat and essential nutrients.

However, scientists do not know the working mechanism of "fasting to reverse aging." Professor Stephen Helfand believes that Sirtuins protein is likely to play an important role in it.

"We believe that Sirt4 is a potential target that helps improve metabolic diseases and is expected to prolong healthy life. Our current research is still limited to fruit flies, and how it will be activated in humans in the future will require more research." Stephen Helfand said.

Studies have shown that resveratrol activates Sirt1 protein. Now, scientists want to know who is responsible for activating Sirt4.

References: 1) Boosting Sirt4 gene activity extends healthy lifespan in fruit flies

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