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Evolution of Human Longevity Uncoupled from Caloric Restriction Mechanisms
Caloric restriction (CR) and chemical agents, such as resveratrol and rapamycin that partially mimic the CR effect, can delay morbidity and mortality across a broad range of species. In humans, however, the effects of CR or other life-extending agents have not yet been investigated systematically. H...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3882206/ https://www.ncbi.nlm.nih.gov/pubmed/24400080 http://dx.doi.org/10.1371/journal.pone.0084117 |
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author | Zhao, Guodong Guo, Song Somel, Mehmet Khaitovich, Philipp |
author_facet | Zhao, Guodong Guo, Song Somel, Mehmet Khaitovich, Philipp |
author_sort | Zhao, Guodong |
collection | PubMed |
description | Caloric restriction (CR) and chemical agents, such as resveratrol and rapamycin that partially mimic the CR effect, can delay morbidity and mortality across a broad range of species. In humans, however, the effects of CR or other life-extending agents have not yet been investigated systematically. Human maximal lifespan is already substantially greater compared to that of closely related primate species. It is therefore possible that humans have acquired genetic mutations that mimic the CR effect. Here, we tested this notion by comparing transcriptome differences between humans and other primates, with the transcriptome changes observed in mice subjected to CR. We show that the human transcriptome state, relative to other primate transcriptomes, does not match that of the CR mice or mice treated with resveratrol, but resembles the transcriptome state of ad libitum fed mice. At the same time, the transcriptome changes induced by CR in mice are enriched among genes showing age-related changes in primates, concentrated in specific expression patterns, and can be linked with specific functional pathways, including insulin signalling, cancer, and the immune response. These findings indicate that the evolution of human longevity was likely independent of CR-induced lifespan extension mechanisms. Consequently, application of CR or CR-mimicking agents may yet offer a promising direction for the extension of healthy human lifespan. |
format | Online Article Text |
id | pubmed-3882206 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38822062014-01-07 Evolution of Human Longevity Uncoupled from Caloric Restriction Mechanisms Zhao, Guodong Guo, Song Somel, Mehmet Khaitovich, Philipp PLoS One Research Article Caloric restriction (CR) and chemical agents, such as resveratrol and rapamycin that partially mimic the CR effect, can delay morbidity and mortality across a broad range of species. In humans, however, the effects of CR or other life-extending agents have not yet been investigated systematically. Human maximal lifespan is already substantially greater compared to that of closely related primate species. It is therefore possible that humans have acquired genetic mutations that mimic the CR effect. Here, we tested this notion by comparing transcriptome differences between humans and other primates, with the transcriptome changes observed in mice subjected to CR. We show that the human transcriptome state, relative to other primate transcriptomes, does not match that of the CR mice or mice treated with resveratrol, but resembles the transcriptome state of ad libitum fed mice. At the same time, the transcriptome changes induced by CR in mice are enriched among genes showing age-related changes in primates, concentrated in specific expression patterns, and can be linked with specific functional pathways, including insulin signalling, cancer, and the immune response. These findings indicate that the evolution of human longevity was likely independent of CR-induced lifespan extension mechanisms. Consequently, application of CR or CR-mimicking agents may yet offer a promising direction for the extension of healthy human lifespan. Public Library of Science 2014-01-06 /pmc/articles/PMC3882206/ /pubmed/24400080 http://dx.doi.org/10.1371/journal.pone.0084117 Text en © 2014 Zhao et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Zhao, Guodong Guo, Song Somel, Mehmet Khaitovich, Philipp Evolution of Human Longevity Uncoupled from Caloric Restriction Mechanisms |
title | Evolution of Human Longevity Uncoupled from Caloric Restriction Mechanisms |
title_full | Evolution of Human Longevity Uncoupled from Caloric Restriction Mechanisms |
title_fullStr | Evolution of Human Longevity Uncoupled from Caloric Restriction Mechanisms |
title_full_unstemmed | Evolution of Human Longevity Uncoupled from Caloric Restriction Mechanisms |
title_short | Evolution of Human Longevity Uncoupled from Caloric Restriction Mechanisms |
title_sort | evolution of human longevity uncoupled from caloric restriction mechanisms |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3882206/ https://www.ncbi.nlm.nih.gov/pubmed/24400080 http://dx.doi.org/10.1371/journal.pone.0084117 |
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