Haploinsufficiency of akt1 prolongs the lifespan of mice.

There is increasing evidence that nutrient-sensing machinery is critically involved in the regulation of aging. The insulin/insulin-like growth factor-1 signaling pathway is the best-characterized pathway with an influence on longevity in a variety of organisms, ranging from yeast to rodents. Reduce...

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Autores principales:	Aika Nojima, Masakatsu Yamashita, Yohko Yoshida, Ippei Shimizu, Harumi Ichimiya, Naomi Kamimura, Yoshio Kobayashi, Shigeo Ohta, Naoaki Ishii, Tohru Minamino
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e04105dc4ed44a10b29229bac99f9b10
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spelling	oai:doaj.org-article:e04105dc4ed44a10b29229bac99f9b102021-11-18T09:02:03ZHaploinsufficiency of akt1 prolongs the lifespan of mice.1932-620310.1371/journal.pone.0069178https://doaj.org/article/e04105dc4ed44a10b29229bac99f9b102013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23935948/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203There is increasing evidence that nutrient-sensing machinery is critically involved in the regulation of aging. The insulin/insulin-like growth factor-1 signaling pathway is the best-characterized pathway with an influence on longevity in a variety of organisms, ranging from yeast to rodents. Reduced expression of the receptor for this pathway has been reported to prolong the lifespan; however, the underlying mechanisms are largely unknown. Here we show that haploinsufficiency of Akt1 leads to an increase of the lifespan in mice. Akt1 (+/-) mice had a lower body weight than their littermates with less fat mass and normal glucose metabolism. Ribosomal biogenesis and the mitochondrial DNA content were significantly reduced in these mice, along with a decrease of oxidative stress. Consistent with the results obtained in mice, inhibition of Akt-1 promoted longevity in nematodes (Caenorhabditis elegans), whereas activation of Akt-1 shortened the lifespan. Inhibition of Akt-1 led to a decrease of ribosomal gene expression and the mitochondrial DNA content in both human cells and nematodes. Moreover, deletion of ribosomal gene expression resulted in a decrease of the mitochondrial DNA content and normalized the lifespan shortened by Akt-1 activation in nematodes. These results suggest that an increase of mitochondrial amount and energy expenditure associated with enhanced protein synthesis accelerates both aging and the onset of age-associated diseases.Aika NojimaMasakatsu YamashitaYohko YoshidaIppei ShimizuHarumi IchimiyaNaomi KamimuraYoshio KobayashiShigeo OhtaNaoaki IshiiTohru MinaminoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e69178 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Aika Nojima Masakatsu Yamashita Yohko Yoshida Ippei Shimizu Harumi Ichimiya Naomi Kamimura Yoshio Kobayashi Shigeo Ohta Naoaki Ishii Tohru Minamino Haploinsufficiency of akt1 prolongs the lifespan of mice.
description	There is increasing evidence that nutrient-sensing machinery is critically involved in the regulation of aging. The insulin/insulin-like growth factor-1 signaling pathway is the best-characterized pathway with an influence on longevity in a variety of organisms, ranging from yeast to rodents. Reduced expression of the receptor for this pathway has been reported to prolong the lifespan; however, the underlying mechanisms are largely unknown. Here we show that haploinsufficiency of Akt1 leads to an increase of the lifespan in mice. Akt1 (+/-) mice had a lower body weight than their littermates with less fat mass and normal glucose metabolism. Ribosomal biogenesis and the mitochondrial DNA content were significantly reduced in these mice, along with a decrease of oxidative stress. Consistent with the results obtained in mice, inhibition of Akt-1 promoted longevity in nematodes (Caenorhabditis elegans), whereas activation of Akt-1 shortened the lifespan. Inhibition of Akt-1 led to a decrease of ribosomal gene expression and the mitochondrial DNA content in both human cells and nematodes. Moreover, deletion of ribosomal gene expression resulted in a decrease of the mitochondrial DNA content and normalized the lifespan shortened by Akt-1 activation in nematodes. These results suggest that an increase of mitochondrial amount and energy expenditure associated with enhanced protein synthesis accelerates both aging and the onset of age-associated diseases.
format	article
author	Aika Nojima Masakatsu Yamashita Yohko Yoshida Ippei Shimizu Harumi Ichimiya Naomi Kamimura Yoshio Kobayashi Shigeo Ohta Naoaki Ishii Tohru Minamino
author_facet	Aika Nojima Masakatsu Yamashita Yohko Yoshida Ippei Shimizu Harumi Ichimiya Naomi Kamimura Yoshio Kobayashi Shigeo Ohta Naoaki Ishii Tohru Minamino
author_sort	Aika Nojima
title	Haploinsufficiency of akt1 prolongs the lifespan of mice.
title_short	Haploinsufficiency of akt1 prolongs the lifespan of mice.
title_full	Haploinsufficiency of akt1 prolongs the lifespan of mice.
title_fullStr	Haploinsufficiency of akt1 prolongs the lifespan of mice.
title_full_unstemmed	Haploinsufficiency of akt1 prolongs the lifespan of mice.
title_sort	haploinsufficiency of akt1 prolongs the lifespan of mice.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/e04105dc4ed44a10b29229bac99f9b10
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Haploinsufficiency of akt1 prolongs the lifespan of mice.

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