Verlingue2016 - Signalling pathway that control S-phase entry and geroconversion - Boolean Model

Verlingue2016 - Signalling pathway that
control S-phase entry and geroconversion - Boolean Model

This model is described in the article:

A comprehensive approach to
the molecular determinants of lifespan using a Boolean model of
geroconversion.

Verlingue L, Dugourd A, Stoll G,
Barillot E, Calzone L, Londoño-Vallejo A.
Aging Cell 2016 Sep; :
Abstract:

Altered molecular responses to insulin and growth factors
(GF) are responsible for late-life shortening diseases such as
type-2 diabetes mellitus (T2DM) and cancers. We have built a
network of the signaling pathways that control S-phase entry
and a specific type of senescence called geroconversion. We
have translated this network into a Boolean model to study
possible cell phenotype outcomes under diverse molecular
signaling conditions. In the context of insulin resistance, the
model was able to reproduce the variations of the senescence
level observed in tissues related to T2DM's main morbidity and
mortality. Furthermore, by calibrating the pharmacodynamics of
mTOR inhibitors, we have been able to reproduce the
dose-dependent effect of rapamycin on liver degeneration and
lifespan expansion in wild-type and HER2-neu mice. Using the
model, we have finally performed an in silico prospective
screen of the risk-benefit ratio of rapamycin dosage for
healthy lifespan expansion strategies. We present here a
comprehensive prognostic and predictive systems biology tool
for human aging.

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