| First Author | van Gastel J | Year | 2019 |
| Journal | Mech Ageing Dev | Volume | 184 |
| Pages | 111150 | PubMed ID | 31574270 |
| Mgi Jnum | J:293322 | Mgi Id | MGI:6452528 |
| Doi | 10.1016/j.mad.2019.111150 | Citation | van Gastel J, et al. (2019) Multidimensional informatic deconvolution defines gender-specific roles of hypothalamic GIT2 in aging trajectories. Mech Ageing Dev 184:111150 |
| abstractText | 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. |
