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Title
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Multidimensional informatic deconvolution defines gender-specific roles of hypothalamic GIT2 in aging trajectories
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Author
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Abstract
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| In most species, females live longer than males. An understanding of this female longevity advantage will likely uncover novel anti-aging therapeutic targets. Here we investigated the transcriptomic responses in the hypothalamus - a key organ for somatic aging control - to the introduction of a simple aging-related molecular perturbation, i.e. GIT2 heterozygosity. Our previous work has demonstrated that GIT2 acts as a network controller of aging. A similar number of both total (1079-female, 1006-male) and gender-unique (577-female, 527-male) transcripts were significantly altered in response to GIT2 heterozygosity in early life-stage (2 month-old) mice. Despite a similar volume of transcriptomic disruption in females and males, a considerably stronger dataset coherency and functional annotation representation was observed for females. It was also evident that female mice possessed a greater resilience to pro-aging signaling pathways compared to males. Using a highly data-dependent natural language processing informatics pipeline, we identified novel functional data clusters that were connected by a coherent group of multifunctional transcripts. From these it was clear that females prioritized metabolic activity preservation compared to males to mitigate this pro-aging perturbation. These findings were corroborated by somatic metabolism analyses of living animals, demonstrating the efficacy of our new informatics pipeline. |
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Language
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English
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Source (journal)
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Mechanisms of ageing and development. - Lausanne
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Publication
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Lausanne
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2019
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ISSN
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0047-6374
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DOI
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10.1016/J.MAD.2019.111150
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Volume/pages
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184
(2019)
, 20 p.
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Article Reference
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111150
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ISI
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000501657500001
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Pubmed ID
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31574270
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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