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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