Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Caloric restriction extends yeast chronological lifespan via a mechanism linking cellular aging to cell cycle regulation maintenance of a quiescent state entry into a nonquiescent state and survival in the nonquiescent state

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Oncotarget. 2017; 8:69328-69350. https://doi.org/10.18632/oncotarget.20614

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Anna Leonov1, Rachel Feldman1, Amanda Piano1, Anthony Arlia-Ciommo1, Vicky Lutchman1, Masoumeh Ahmadi1, Sarah Elsaser1, Hana Fakim1, Mahdi Heshmati-Moghaddam1, Asimah Hussain1, Sandra Orfali1, Harshvardhan Rajen1, Negar Roofigari-Esfahani1, Leana Rosanelli1 and Vladimir I. Titorenko1

1 Department of Biology, Concordia University, Montreal, Quebec, Canada

Correspondence to:

Vladimir I. Titorenko, email:

Keywords: yeast, cellular aging, cell cycle, cell differentiation, cell quiescence, Gerotarget 

Received: June 12, 2017 Accepted: August 14, 2017 Published: September 01, 2017

Abstract

A yeast culture grown in a nutrient-rich medium initially containing 2% glucose is not limited in calorie supply. When yeast cells cultured in this medium consume glucose, they undergo cell cycle arrest at a checkpoint in late G1 and differentiate into quiescent and non-quiescent cell populations. Studies of such differentiation have provided insights into mechanisms of yeast chronological aging under conditions of excessive calorie intake. Caloric restriction is an aging-delaying dietary intervention. Here, we assessed how caloric restriction influences the differentiation of chronologically aging yeast cultures into quiescent and non-quiescent cells, and how it affects their properties. We found that caloric restriction extends yeast chronological lifespan via a mechanism linking cellular aging to cell cycle regulation, maintenance of quiescence, entry into a non-quiescent state and survival in this state. Our findings suggest that caloric restriction delays yeast chronological aging by causing specific changes in the following: 1) a checkpoint in G1 for cell cycle arrest and entry into a quiescent state; 2) a growth phase in which high-density quiescent cells are committed to become low-density quiescent cells; 3) the differentiation of low-density quiescent cells into low-density non-quiescent cells; and 4) the conversion of high-density quiescent cells into high-density non-quiescent cells.