Two paths of aging: New insights on promoting healthspan
Master aging circuit identified

Date:
July 16, 2020
Source:
University of California - San Diego
Summary:
Scientists have unraveled key mechanisms behind the mysteries
of aging.

They isolated two distinct paths that cells travel during aging
and engineered a new way to genetically program these processes
to extend lifespan. Cells embark upon either a nucleolar or
mitochondrial path early in life, and follow this ''aging route''
throughout their entire lifespan through decline and death. At the
heart of the controls the researchers found a master circuit that
guides these aging processes.



FULL STORY ========================================================================== Molecular biologists and bioengineers at the University of California San
Diego have unraveled key mechanisms behind the mysteries of aging. They isolated two distinct paths that cells travel during aging and engineered
a new way to genetically program these processes to extend lifespan.


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

Our lifespans as humans are determined by the aging of our individual
cells. To understand whether different cells age at the same rate and
by the same cause, the researchers studied aging in the budding yeast Saccharomyces cerevisiae, a tractable model for investigating mechanisms
of aging, including the aging paths of skin and stem cells.

The scientists discovered that cells of the same genetic material
and within the same environment can age in strikingly distinct
ways, their fates unfolding through different molecular and cellular trajectories. Using microfluidics, computer modeling and other techniques,
they found that about half of the cells age through a gradual decline
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 age due to dysfunction of their mitochondria, the energy production units of cells.

The cells embark upon either the nucleolar or mitochondrial path early
in life, and follow this "aging route" throughout their entire lifespan
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 route and the connections among them,
revealing a molecular circuit that controls cell aging, analogous to
electric circuits that control home appliances," said Nan Hao, senior
author of the study and an associate professor in the Section of Molecular Biology, Division of Biological Sciences.

Having developed a new model of the aging landscape, Hao and his
coauthors found they could manipulate and ultimately optimize the aging process. Computer simulations helped the researchers reprogram the master molecular circuit by modifying its DNA, allowing them to genetically
create a novel aging route that features a dramatically extended 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,"
said Hao.

The researchers will now test their new model in more complex cells and organisms and eventually in human cells to seek similar aging routes. They
also plan to test chemical techniques and evaluate how combinations of therapeutics and drug "cocktails" might guide pathways to longevity.

"Much of the work featured in this paper benefits from a strong interdisciplinary team that was assembled," said Biological Sciences
Professor of Molecular Biology Lorraine Pillus, one of the study's
coauthors. "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."

========================================================================== Story Source: Materials provided by
University_of_California_-_San_Diego. Original written by Mario
Aguilera. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Yang Li, Yanfei Jiang, Julie Paxman, Richard O'laughlin, Stephen
Klepin,
Yuelian Zhu, Lorraine Pillus, Lev S. Tsimring, Jeff Hasty, Nan
Hao. A programmable fate decision landscape underlies single-cell
aging in yeast. Science, 2020 DOI: 10.1126/science.aax9552 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200716144732.htm

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