Researchers discover 2 ways of aging and new insights on health promotion

Molecular biologists and bioengineers at the University of California, San Diego have discovered key mechanisms behind the mysteries of aging. They isolated two different pathways that cells travel through aging and designed a new way to genetically program these processes to extend shelf life.

The research is described July 17 in the journal. Science.

Our life expectancy as humans is determined by the aging of our individual cells. To understand whether different cells age at the same rate and for the same cause, the researchers studied aging in budding yeast Saccharomyces cerevisiae, a manageable model to investigate the mechanisms of aging, including skin and cell aging pathways. mother.

Scientists discovered that cells in the same genetic material and within the same environment can age in surprisingly different ways, their destinies unfolding through different molecular and cellular pathways. Using microfluidics, computer modeling, and other techniques, they found that about half of cells age through a gradual decrease in the stability of the nucleolus, a region of nuclear DNA where key components of protein-producing “factories” are synthesized. In contrast, the other half aged due to dysfunction of their mitochondria, the cells’ energy-producing units.

Cells embark on the nucleolar or mitochondrial pathway early in life, and follow this “aging pathway” throughout their lives through decline and death. At the heart of the controls, the researchers found a master circuit that guides these aging processes.

“To understand how cells make these decisions, we identified the molecular processes underlying each aging pathway and the connections between them, revealing a molecular circuitry that controls cellular aging, analogous to the electrical circuits that control household appliances,” Nan said. Hao, lead author of The Study and an associate professor in the Molecular Biology Section, Division of Biological Sciences.

Having developed a new model of the aging landscape, Hao and his co-authors discovered that they could manipulate and ultimately optimize the aging process. Computer simulations helped the researchers reprogram the master molecular circuitry by modifying its DNA, allowing them to genetically create a new aging pathway that has a dramatically extended lifespan.

“Our study raises the possibility of rationally designing genetic or chemical therapies to reprogram how human cells age, with the goal of effectively delaying human aging and extending human health,” said Hao.

The researchers will now test their new model on more complex cells and organisms, and eventually human cells, to look for similar aging pathways. They also plan to test chemical techniques and evaluate how combinations of drug “cocktails” and therapies could guide pathways to longevity.

“Much of the work presented in this paper benefits from a strong interdisciplinary team that came together,” said molecular biology professor of molecular biology, Lorraine Pillus, one of the study’s co-authors. “A great aspect of the team is that we not only do the modeling but we also do the experimentation to determine if the model is correct or not. These iterative processes are critical to the work we are doing.”