The yeast forkhead HCM1 controls life span independent of calorie restriction

Noam Maoz; Orshay Gabay; Hiba Waldman Ben-Asher; Haim Y. Cohen

doi:10.1093/gerona/glu059

The yeast forkhead HCM1 controls life span independent of calorie restriction

Noam Maoz, Orshay Gabay, Hiba Waldman Ben-Asher, Haim Y. Cohen

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Abstract

Regulation of life span by members of the forkhead transcription factor family of proteins is one of the most highly investigated pathways in the field of aging. Nevertheless, despite the existence of forkhead family homologues in yeast, our knowledge of these proteins' role in yeast longevity is limited. Here, we show that yeast Hcm1p forkhead is the closest homologue of the worm PHA-4 forkhead, which regulates Caenorhabditis elegans life span. Overexpressing the yeast forkhead HCM1 or its deficiency resulted in a significant extension or reduction in yeast replicative life span, respectively. HCM1 regulates stress resistance, significantly increases the mRNA levels of several stress response genes including the catalase enzymes CTA1 and CTT1, and positively regulates life span independently of calorie restriction. Thus, HCM1 is a key regulator of life span, through a mechanism independent of calorie restriction.

Original language	English
Pages (from-to)	444-453
Number of pages	10
Journal	Journals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume	70
Issue number	4
DOIs	https://doi.org/10.1093/gerona/glu059
State	Published - 1 Apr 2015

Bibliographical note

Funding Information:
Funding This study was supported by the Israel Science Foundation (62113), I-Core Foundation (41/11), Israeli Ministry of Health (3-9194), Teva Pharmaceutical Industries LTD (1237680), and the ERC: European Research Council (242763).

Publisher Copyright:
© 2014 The Author.

Keywords

Aging
Forkhead
HCM1

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10.1093/gerona/glu059

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abstract = "Regulation of life span by members of the forkhead transcription factor family of proteins is one of the most highly investigated pathways in the field of aging. Nevertheless, despite the existence of forkhead family homologues in yeast, our knowledge of these proteins' role in yeast longevity is limited. Here, we show that yeast Hcm1p forkhead is the closest homologue of the worm PHA-4 forkhead, which regulates Caenorhabditis elegans life span. Overexpressing the yeast forkhead HCM1 or its deficiency resulted in a significant extension or reduction in yeast replicative life span, respectively. HCM1 regulates stress resistance, significantly increases the mRNA levels of several stress response genes including the catalase enzymes CTA1 and CTT1, and positively regulates life span independently of calorie restriction. Thus, HCM1 is a key regulator of life span, through a mechanism independent of calorie restriction.",

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AB - Regulation of life span by members of the forkhead transcription factor family of proteins is one of the most highly investigated pathways in the field of aging. Nevertheless, despite the existence of forkhead family homologues in yeast, our knowledge of these proteins' role in yeast longevity is limited. Here, we show that yeast Hcm1p forkhead is the closest homologue of the worm PHA-4 forkhead, which regulates Caenorhabditis elegans life span. Overexpressing the yeast forkhead HCM1 or its deficiency resulted in a significant extension or reduction in yeast replicative life span, respectively. HCM1 regulates stress resistance, significantly increases the mRNA levels of several stress response genes including the catalase enzymes CTA1 and CTT1, and positively regulates life span independently of calorie restriction. Thus, HCM1 is a key regulator of life span, through a mechanism independent of calorie restriction.

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The yeast forkhead HCM1 controls life span independent of calorie restriction

Abstract

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Keywords

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