TORC1 signaling inhibition by rapamycin and caffeine affect lifespan, global gene expression, and cell proliferation of fission yeast

Article


Rallis, C., Codlin, Sandra and Bähler, Jürg 2013. TORC1 signaling inhibition by rapamycin and caffeine affect lifespan, global gene expression, and cell proliferation of fission yeast. Aging Cell. 12 (4), pp. 563-573.
AuthorsRallis, C., Codlin, Sandra and Bähler, Jürg
Abstract

Target of rapamycin complex 1 (TORC1) is implicated in growth
control and aging from yeast to humans. Fission yeast is
emerging as a popular model organism to study TOR signaling,
although rapamycin has been thought to not affect cell growth in
this organism. Here, we analyzed the effects of rapamycin and
caffeine, singly and combined, on multiple cellular processes in
fission yeast. The two drugs led to diverse and specific phenotypes
that depended on TORC1 inhibition, including prolonged
chronological lifespan, inhibition of global translation, inhibition
of cell growth and division, and reprograming of global gene
expression mimicking nitrogen starvation. Rapamycin and caffeine
differentially affected these various TORC1-dependent
processes. Combined drug treatment augmented most phenotypes
and effectively blocked cell growth. Rapamycin showed a
much more subtle effect on global translation than did caffeine,
while both drugs were effective in prolonging chronological
lifespan. Rapamycin and caffeine did not affect the lifespan via
the pH of the growth media. Rapamycin prolonged the lifespan
of nongrowing cells only when applied during the growth phase
but not when applied after cells had stopped proliferation. The
doses of rapamycin and caffeine strongly correlated with growth
inhibition and with lifespan extension. This comprehensive
analysis will inform future studies into TORC1 function and
cellular aging in fission yeast and beyond.
Key words: cell proliferation; chronological aging; gene regulation;
Schizosaccharomyces pombe; Target of Rapamycin;
translation.

JournalAging Cell
Journal citation12 (4), pp. 563-573
ISSN14749718
Year2013
PublisherWiley Open Access for Anatomical Society of Great Britain and Ireland
Publisher's version
License
CC BY
Digital Object Identifier (DOI)doi:10.1111/acel.12080
Web address (URL)https://doi.org/10.1111/acel.12080
Publication dates
Online02 May 2013
Publication process dates
Deposited13 Feb 2018
Accepted11 Mar 2013
Accepted11 Mar 2013
FunderBiotechnology and Biological Sciences Research Council
Wellcome Trust
Copyright information© 2013 The authors
LicenseCC BY 3.0
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