Calorie Restriction Increases the Number of Competing Stem Cells and Decreases Mutation Retention in the Intestine.

Cell Reports
Lotte BruensJacco van Rheenen

Abstract

Calorie restriction (CR) extends lifespan through several intracellular mechanisms, including increased DNA repair, leading to fewer DNA mutations that cause age-related pathologies. However, it remains unknown how CR acts on mutation retention at the tissue level. Here, we use Cre-mediated DNA recombination of the confetti reporter as proxy for neutral mutations and follow these mutations by intravital microscopy to identify how CR affects retention of mutations in the intestine. We find that CR leads to increased numbers of functional Lgr5+ stem cells that compete for niche occupancy, resulting in slower but stronger stem cell competition. Consequently, stem cells carrying neutral or Apc mutations encounter more wild-type competitors, thus increasing the chance that they get displaced from the niche to get lost over time. Thus, our data show that CR not only affects the acquisition of mutations but also leads to lower retention of mutations in the intestine.

References

Dec 1, 1974·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·I W McLean, P K Nakane
Jul 5, 1996·Science·R S Sohal, R Weindruch
Oct 28, 1999·Neurobiology of Aging·T D PughR Weindruch
Nov 24, 2001·Nature·A BartkeG S Roth
Oct 19, 2007·Nucleic Acids Research·Ahmad R HeydariArlan Richardson
Jul 11, 2009·Science·Ricki J ColmanRichard Weindruch
Jun 12, 2013·Cell·Carlos López-OtínGuido Kroemer
Nov 23, 2013·Science·Louis VermeulenDouglas J Winton
Jan 21, 2015·Cell·Marisa M MerinoEduardo Moreno
Aug 9, 2016·Annual Review of Cell and Developmental Biology·Cristina Clavería, Miguel Torres
May 30, 2017·Gastroenterology·Lotte BruensHugo J Snippert
May 17, 2019·Nature·Stephanie J EllisElaine Fuchs

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Citations

Mar 24, 2021·Developmental Biology·Mariana Marques-Reis, Eduardo Moreno
Jul 28, 2021·Current Biology : CB·Koki KohashiYasuyuki Fujita
Oct 12, 2021·Current Opinion in Genetics & Development·Takeshi Maruyama, Yasuyuki Fujita

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Methods Mentioned

BETA
imaging technique

Software Mentioned

Leica LasX
GraphPad Prism
RNAScope
Fiji

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