Cellular aging ‘master circuit’ discovered: Extended human lifespan to follow?

Cellular aging ‘master circuit’ discovered: Extended human lifespan to follow?
by John Anderer July 19, 2020
SAN DIEGO — The average American lives to be around 75 or 80 years old; but if you had an opportunity to slow down the aging process and live an extra couple of decades would you take it? It’s a loaded question, strife with philosophical, religious, and societal considerations. Humans have pondered the possibilities of extended, or even immortal, life for as long as we’ve inhabited this planet. But at the end of the day it’s all just a daydream, right?
Not necessarily, according to new research out of the University of California, San Diego. The study, led by UCSD molecular biologists and bioengineers, produced a groundbreaking discovery regarding the intricacies of cellular aging. In light of their findings, researchers say the notion of “dramatically” extending human life isn’t so farfetched after all.
Yeast cells with the same DNA under the same environment show different structures of mitochondria (green) and nucleolus (red), which may underlie the causes of different aging paths. Single and double arrowheads point to two cells with distinct mitochondrial and nucleolar morphologies. (Image courtesy: Hao Lab, UC San Diego)
Each human’s lifespan and personal rate of aging is determined by the aging of their individual cells. Originally, the study’s authors just wanted to investigate if different types of cells age at different speeds based on different stimuli/causes. To that end, they studied aging in the budding yeast Saccharomyces cerevisiae. This provided a suitable model with which to track aging mechanisms of various cell types.
Two different paths of aging
The research ultimately finds that two cells made of the exact same genetic material, and residing in the same bodily location, can age in vastly different ways and molecular/cellular trajectories. This finding, of course, warranted further research. So, via a variety of complex techniques, researchers discovered that about half of the cells age due to a slow decline in the stability of their nucleus. Meanwhile, the other cells appear to age primarily because of dysfunctioning mitochondria.
Cells seem to start off on either the nucleolar or mitochondrial path of aging very early on in their existence. They continue to follow that same aging process until death. Very importantly, researchers say they were able to find the “master circuit” in charge of controlling these aging processes and paths among cells.
“To understand how cells make these decisions, we identified the molecular processes underlying each aging route and the connections among them, revealing a molecular circuit that controls cell aging, analogous to electric circuits that control home appliances,” says senior study author Nan Hao, an associate professor in the Section of Molecular Biology, Division of Biological Sciences, in a release.
Extending human healthspan
This discovery allowed the study’s authors to construct a new model of the “aging landscape.” This new perspective led to a revelation: Hao and his team believe they can conceivably manipulate and optimize the aging process. Using a series of computer simulations, the research team reprogrammed the master molecular circuit via DNA modification. This facilitated the creation of a new, novel aging route offering a much longer lifespan.
“Our study raises the possibility of rationally designing gene or chemical-based therapies to reprogram how human cells age, with a goal of effectively delaying human aging and extending human healthspan,” Hao says.
Next, researchers want to continue testing their new model on more complex cells before eventually upgrading to human cells.
“Much of the work featured in this paper benefits from a strong interdisciplinary team that was assembled,” says Biological Sciences Professor of Molecular Biology Lorraine Pillus, a study co-author. “One great aspect of the team is that we not only do the modeling but we then do the experimentation to determine whether the model is correct or not. These iterative processes are critical for the work that we are doing.”
The study is published in Science.


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