The role of mitochondria in cell aging
LifeSciencesToday based on materials from Newcastle University: Mitochondria shown to trigger cell aging
A study published in The EMBO Journal (Correia‐Melo et al., Mitochondria are required for pro-aging features of the senescent phenotype), conducted at the University of Newcastle (Newcastle University) under the leadership of Dr. Joao Passos, found evidence that the removal of mitochondria leads to the rejuvenation of aging cells. This experiment for the first time convincingly proves that mitochondria are the trigger of senescence. The discovery of British scientists brings us closer to the development of anti-aging treatment methods, which will be based on targeting mitochondria.
Scientists conducted a series of genetic experiments on human cells grown in the laboratory and were able to remove most, if not all, mitochondria from the senescent cells. Normally, cells themselves can destroy defective mitochondria through a biochemical mechanism known as mitophagy. But the researchers managed to "trick" the cells – to induce this process in them on a larger scale.
To their surprise, they observed that after the loss of mitochondria, the senescent cells showed characteristics similar to those of young cells, that is, they became younger. The levels of inflammation–related molecules and reactive oxygen species (ROS), as well as the expression levels of certain genes – all these indicators are considered markers of senescence - have fallen to values that would be expected from younger cells.
"This is a very interesting and surprising discovery. We already had some information that mitochondria play a role in senescence, but scientists around the world have been trying to understand exactly how and to what extent they are involved in this process," says Dr. Passos (The Newcastle University Institute for Aging) about his work. "These new findings highlight that mitochondria are indeed essential for cell aging."
Senescence is an important anticancer mechanism, but it also contributes to aging. A study by British and American scientists shows that mitochondria are necessary for the pro-inflammatory phenotype of senescent cells and that senescence can be induced by mitochondrial biogenesis. The new signaling pathway of cellular aging includes ATM, Akt, mTOR and PGC‐1ß-mediated mitochondrial biogenesis. Mitochondrial biogenesis stabilizes senescence through a positive feedback chain including reactive oxygen species (ROS) and DNA damage response (DDR). In several models of aging, the absence of mitochondria reduces the spectrum of effectors and phenotypes of aging while maintaining ATP synthesis due to increased glycolysis. Global analysis of the transcriptome by RNA sequencing has shown that the overwhelming number of changes associated with senescence, in particular, the proinflammatory phenotype, depends on mitochondria. Mechanistically, the phosphorylation cascade of ATM, Akt and mTORC1 integrates signals from DDR and induces PGC-1-dependent mitochondrial biogenesis, contributing to ROS-mediated activation of DDR and cell cycle suspension. Reducing the number of mitochondria in vivo by either inhibiting mTORC1 or deleting PGC-1ß prevents senescence in the liver of aging mice. (Fig. The EMBO Journal)
Dr. Passos and his colleagues from other British and American universities managed to decipher the mechanism by which mitochondria contribute to cell aging. They discovered that one of the main factors of senescence is mitochondrial biogenesis, a complex process of formation of new mitochondria.
"For the first time, the study shows that mitochondria are necessary for cell aging," says the study's lead author, Dr. Clara Correia-Melo. "Now we are one step closer to developing anti-aging cell therapies that target mitochondria."
The study was funded by the Biotechnology and Biological Sciences Research Council (BBSRC).
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10.03.2016