1. Aging Cell. 2013 Aug;12(4):563-73. doi: 10.1111/acel.12080. Epub 2013 May 2.

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

Rallis C(1), Codlin S, Bähler J.

Author information: 
(1)Department of Genetics, Evolution & Environment and Institute of Healthy
Ageing, University College London, Gower Street - Darwin Building, London, WC1E
6BT, UK.

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.

© 2013 The Authors. Aging Cell published by John Wiley & Sons Ltd and the
Anatomical Society.

DOI: 10.1111/acel.12080 
PMCID: PMC3798131
PMID: 23551936  [Indexed for MEDLINE]