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Ageing signalling pathways: Quantifying the effects of protein interactions
Author(s) -
Sadria Mehrshad,
Layton Anita
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.01894
Subject(s) - mtorc1 , pi3k/akt/mtor pathway , sirtuin , ageing , ampk , calorie restriction , biology , longevity , mechanistic target of rapamycin , resveratrol , nutrient sensing , sirtuin 1 , mtorc2 , neuroscience , microbiology and biotechnology , autophagy , signal transduction , protein kinase a , nad+ kinase , phosphorylation , genetics , gene , pharmacology , biochemistry , downregulation and upregulation , endocrinology , apoptosis , enzyme
Cells adapt their metabolism and activities in response to signals from their surroundings, and this ability is essential for their survival in the face of environmental changes. In mammalian tissues a deficit of these mechanisms is commonly associated with cellular aging and degenerative diseases related to aging, such as cardiovascular disease, cancer, immune system decline, and neurological pathologies. Several proteins have been identified as being able to respond directly to energy, nutrient, and growth factor levels and stress stimuli in order to mediate adaptations in the cell. In particular, mTOR, AMPK, and sirtuins are known to play an essential role in the management of metabolic stress and in the mechanisms and metabolism of ageing of mammals. Given that the ageing process remains to be completely understood, the goal of this study is to gain insights into the interactions of the proteins in the ageing‐related signalling pathways, and how those interactions may impact longevity and related diseases. To achieve that goal, we have developed a computational model of ageing signalling pathways. Specifically, the insulin growth factor/mTOR pathway and the sirtuin pathway are represented. The model simulates the interactions among Akt, mTORC1, AMPK, NAD, and SIRT, and predicts their dynamics. The model can be used as an essential component to simulate gene manipulation, therapies (e.g., resveratrol and curcumin), calorie restrictions, and chronic stress, and assess their functional implications on longevity and ageing‐related diseases. Support or Funding Information This research was supported in part by the Canada 150 Research Chair program.