The main mechanism behind the elucidated aging process

Researchers at the University of California, San Diego say they have uncovered the major mechanisms behind the aging process. They isolated two distinct pathways by which cells travel during aging and designed new ways to genetically program these processes to prolong life.

Their research,Prospects for programmable fate decisions underlie single-cell senescence in yeastIs Science..

“Chromatin instability and mitochondrial depletion are conserved processes that contribute to cellular senescence. Both processes have been examined individually in the context of their distinct signaling pathways, but in individual cells. The mechanism that determines which processes govern the aging of the is unknown.

“We show that the interaction between chromatin silencing and the mitochondrial pathway leads to an epigenetic landscape of replicative senescence in yeast with multiple equilibrium states that represent the terminal states of different types of senescence.” Promotes the differentiation of single cells towards one of these states during aging, which determines fate very early and is immune to intracellular noise.”

“Based on a quantitative model of an aging landscape, we genetically engineered a long-lived equilibrium characterized by long life.”

Human life is determined by the aging of individual cells. To understand whether different cells age at the same rate and for the same cause, the researchers studied aging in the budding yeast, Saccharomyces cerevisiae. This is a model for investigating aging mechanisms such as the aging pathways of skin and stem cells.

Scientists have discovered that cells in the same environment with the same genetic material can age in surprisingly different ways. Their fate unfolds through different molecular and cell orbitals. Using microfluidics, computer modeling, and other techniques, it is possible to predict that about half of the cells are senescent due to the gradual loss of stability of the nucleolus where key components of protein production plants are synthesized. discovered. In contrast, the other half year is due to mitochondrial dysfunction.

Cells embark on nucleolar or mitochondrial pathways early in life, following this aging pathway throughout life, leading to decline and death. At the heart of control, researchers have found a master circuit that guides these aging processes.

“To understand how cells make these decisions, we identify the molecular processes that underlie each aging pathway and the connections between them, similar to electrical circuits that control appliances. We have uncovered the molecular circuits that control cell aging,” said Nan Hao, Ph.D., author of senior research and associate professor of the Molecular Biology section of the Biological Sciences Division.

Hao and his co-authors, who developed a new model of the aging situation, have discovered that the aging process can be manipulated and ultimately optimized. Computer simulations have helped researchers reprogram the master molecular circuit by altering DNA, allowing them to genetically create new aging pathways characterized by dramatically long lifespans.

“Our research has the potential to reasonably design genes or chemotherapy to reprogram human cell aging methods with the goal of effectively delaying human aging and prolonging human health. Is increasing,” said Hao.

Researchers are testing new models in more complex cells and organisms, and ultimately human cells, to explore similar aging pathways. They also plan to test chemical techniques and evaluate how the combination of treatments and drug cocktails can lead the way to longevity.

“Many of the studies featured in this paper benefit from a strong, multidisciplinary team assembled,” said one of the co-authors of the study, Professor of Biosciences, Dr. Loraine Pils of Molecular Biology. States. “One of the great things about the team is not only modeling, but experimenting to determine if the model is correct. These iterative processes are important to the work we are doing.”