Cellular aging: A basic paradox elucidated

Date:
November 9, 2021
Source:
University of Montreal Hospital Research Centre (CRCHUM)
Summary:
Cancer researchers show for the first time that cellular
senescence, which occurs when aging cells stop dividing, is caused
by irreversible damage to the genome rather than simply by telomere
erosion.



FULL STORY ==========================================================================
In a study published in Nucleic Acids Research,the team of cancer
researcher Francis Rodier, an Universite' de Montre'al professor, shows
for the first time that cellular senescence, which occurs when aging
cells stop dividing, is caused by irreversible damage to the genome
rather than simply by telomere erosion.


==========================================================================
This discovery goes against the scientific model most widely adopted
in the last 15 years, which is based on one principle: telomeres, caps
located at the ends of chromosomes whose purpose is to protect genetic information, erode with each cell division. When they get too short,
they tell the cell to stop dividing, thus preventing damage to its
DNA. Made dormant, the cell enters senescence.

For this model to be valid, the inactivation of a single telomere should
be sufficient to activate the senescence program. Rodier's laboratory
and many others had already observed that several dysfunctional telomeres
were necessary.

"What's most surprising is that, before really entering senescence, the
cells divide one last time," said Rodier. "In fact, the cell division
caused by telomere dysfunction is so unstable that it ends up creating
genetic defects.

Contrary to what was believed, senescent cells have an abnormal
genome. That's what we show in our study." Snapshots of the life of a
cell To achieve such results, Rodier's research team was able to count
on state-of- the-art imaging equipment funded by the Institut du cancer de?Montre'al.

"Genetically, we were able to reproduce the phenomenon of cellular aging
in the laboratory and ensured that all the telomeres of a population of
cells became dysfunctional," said PhD student Marc-Alexandre Olivier,
co-first author of the study with former colleague Sabrina Ghadaouia,
currently pursuing postdoctoral studies in England. "With our equipment,
we then observed in real time what was happening inside each single cell."
With time, senescent cells build up in the body and are responsible
for the development of diseases such as cancer. This study, therefore,
opens up new research opportunities.

For example, could telomeres be repaired prior to the senescence phase,
thereby preventing cellular aging and genomic instability? The scientific community has been debating this potential cellular rejuvenation for
several years now.

Nevertheless, these emerging therapeutic approaches still need
fine-tuning.

========================================================================== Story Source: Materials provided by University_of_Montreal_Hospital_Research_Centre_(CRCHUM).

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Sabrina Ghadaouia, Marc-Alexandre Olivier, Aure'lie Martinez, Tibila
Kientega, Jian Qin, Patrick Lambert-Lanteigne, Guillaume B Cardin,
Chantal Autexier, Nicolas Malaquin, Francis Rodier. Homologous
recombination-mediated irreversible genome damage underlies
telomere- induced senescence. Nucleic Acids Research, 2021; DOI:
10.1093/nar/ gkab965 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/11/211109095334.htm

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