A new method of prolonging life
Researchers at the University of California at Los Angeles, working under the guidance of Professor David Walker, managed to significantly improve the health and slow down the aging of fruit flies drosophila by manipulating their mitochondria. The authors hope that their proposed approach will delay the development of Parkinson's and Alzheimer's diseases, cancer, stroke, cardiovascular diseases and other age-related diseases in the future.
Mitochondria are the energy centers of the cell, regulating the growth of the cell, as well as determining its fate. As the body ages, the accumulation of damaged mitochondria occurs, and if the cells are unable to get rid of them, such mitochondria become toxic and contribute to the development of a number of age-related pathologies.
During the experiments, the authors found that when fruit flies reach an average age of about 1 month out of the 2-month life cycle of insects, their initially small round mitochondria change their shape, increasing in size and stretching.
This led the researchers to the idea that it is the shape change that deprives the cell of the ability to effectively get rid of damaged mitochondria and leads to their accumulation in the cytoplasm. To test their hypothesis, they increased the expression of the Drp1 protein in the mitochondria of 30-day-old insects for a week, which led to the splitting of enlarged organelles into parts. As a result, only healthy mitochondria of normal shape remained in the cells, and all damaged organelles were destroyed and removed from the cells using the mechanism of autophagy (splitting inside lysosomes). Externally, this was manifested by an increase in the activity, vigor and endurance of insects. At the same time, females lived on average by 20%, and males by 12% longer than the usual lifespan of insects.
Mitochondria (green) of fruit flies aged 10 (top left), 28 (top right) and 37 days (bottom two images). In the lower right image, after increasing the level of the Drp1 protein, the mitochondria returned to the state characteristic of a younger age.
These data indicate the exceptional importance of the Drp1 protein for the aging process. It is known that its concentration decreases significantly with aging, at least in the cells of fruit flies and mice.
In parallel, the authors found that an important role in reversing the process of cellular aging belongs to the Atg1 gene. Inactivation of this gene completely deprived cells of the ability to eliminate damaged mitochondria, even with increased expression of the Drp1 protein.
One of the specific problems that the approach proposed by the authors allows to solve is an increase in intestinal permeability, which develops about a week before the death of fruit flies. Similar age-related changes were also detected in roundworms, mice and monkeys. In their experiments, the authors demonstrated that increasing the expression of Drp1 allows delaying the development of this condition in fruit flies.
In addition, as part of their experiments on fruit flies at an age approximately corresponding to forty human years, the researchers demonstrated that they can increase the lifespan and improve the health of insects by neutralizing the Mfn protein, which gives mitochondria the ability to merge and form large conglomerates.
The long-term goal of this work is to create new drugs capable of reproducing the effects of the Drp1 protein on damaged and deformed mitochondria to increase the life expectancy of people, as well as prolong the period of maintaining good health.
Article by Anil Rana et al. Promoting Drp1-mediated mitochondrial fission in midlife prolongs healthy lifespan of Drosophila melanogaster is published in the journal Nature Communications.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the University of California, Los Angeles: UCLA biologists slow aging, extend lifespan of fruit flies.
07.09.2017