Deletion of Nrip1 Extends Female Mice Longevity, Increases Autophagy, and Delays Cell Senescence

Wang, Jinyu; Chen, Xundi; Osland, Jared M.; Gerber, Skyler J; Luan, Chao; Delfino, Kristin; Goodwin, Leslie O.; Yuan, Rong

doi:10.1093/gerona/glx257

Cited by 21 publications

(20 citation statements)

References 51 publications

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“…In this paper, we used an extensive set of available data from several of our previous studies that investigated longevity‐related phenotypes in a variety of mouse strains, including inbred and genetically modified strains (Wang et al, 2018; Yuan et al, 2012, 2009). Our lifespan study of inbred strains was specifically designed to cover most of the genetic diversity of the mouse ( Mus musculus species, including representatives of four subspecies).…”

Section: Introductionmentioning

confidence: 99%

Genetic differences and longevity‐related phenotypes influence lifespan and lifespan variation in a sex‐specific manner in mice

et al. 2020

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Section: Introductionmentioning

confidence: 99%

Genetic differences and longevity‐related phenotypes influence lifespan and lifespan variation in a sex‐specific manner in mice

et al. 2020

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“…processes [25]. The other hubs of this module are related to ER to Golgi transport, mitochondria, molecule transport, transcriptional regulation, signaling, cell cycle, and metabolic processes.…”

Section: Weighted Gene Co-expression Network Analysis (Wgcna)mentioning

confidence: 99%

Age-related transcriptional modules and TF-miRNA-mRNA interactions in neonatal and infant human thymus

et al. 2020

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The human thymus suffers a transient neonatal involution, recovers and then starts a process of decline between the 1 st and 2 nd years of life. Age-related morphological changes in thymus were extensively investigated, but the genomic mechanisms underlying this process remain largely unknown. Through Weighted Gene Co-expression Network Analysis (WGCNA) and TF-miRNA-mRNA integrative analysis we studied the transcriptome of neonate and infant thymic tissues grouped by age: 0-30 days (A); 31days-6 months (B); 7-12 months (C); 13-18 months (D); 19-31months (E). Age-related transcriptional modules, hubs and high gene significance (HGS) genes were identified, as well as TF-miRNA-hub/HGS co-expression correlations. Three transcriptional modules were correlated with A and/or E groups. Hubs were mostly related to cellular/metabolic processes; few were differentially expressed (DE) or related to T-cell development. Inversely, HGS genes in groups A and E were mostly DE. In A (neonate) one third of the hyper-expressed HGS genes were related to T-cell development, against one-twentieth in E, what may correlate with the early neonatal depletion and recovery of thymic T-cell populations. This genomic mechanism is tightly regulated by TF-miRNA-hub/HGS interactions that differentially govern cellular and molecular processes involved in the functioning of the neonate thymus and in the beginning of thymic decline.

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“…Our data demonstrated a decrease in NRIP1 expression after peptide 14 treatment. Interestingly, the deletion of this gene in old mice resulted in increased autophagy, reduced the number of senescent cells and extended female longevity 66 .…”

Section: Discussionmentioning

confidence: 99%

Senotherapeutic peptide reduces skin biological age and improves skin health markers

Zonari¹,

Le²,

Kz³

et al. 2020

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Skin aging has been primarily related to aesthetics and beauty. Therefore, interventions have focused on reestablishing skin appearance, but not necessarily skin health, function, and resilience. Recently, cellular senescence was shown to play a role in age-related skin function deterioration and influence organismal health and, potentially, longevity. In the present study, a two-step screening was performed to identify peptides capable of reducing cellular senescence in human dermal fibroblasts (HDF) from Hutchinson-Gilford Progeria (HGPS) patients. From the top four peptides of the first round of screening, we built a 764-peptide library using amino acid scanning, of which the second screen led to the identification of peptide 14. Peptide 14 effectively decreased HDF senescence induced by HGPS, chronological aging, ultraviolet-B radiation, and etoposide treatment, without inducing significant cell death, and likely by modulating longevity and senescence pathways. We further validated the effectiveness of peptide 14 using human skin equivalents and skin biopsies, where peptide 14 promoted skin health and reduced senescent cell markers, as well as the biological age of samples, according to the Skin-Specific DNA methylation clock, MolClock. Topical application of peptide 14 outperformed Retinol treatment, the current gold-standard in anti-aging skincare. Finally, we determined that peptide 14 is safe for long-term applications and also significantly extends both the lifespan and healthspan of C. elegans worms tested in two independent testings. This highlights the potential for geroprotective applications of the senotherapeutic compounds identified using our screening platform beyond the skin.

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Deletion of Nrip1 Extends Female Mice Longevity, Increases Autophagy, and Delays Cell Senescence

Cited by 21 publications

References 51 publications

Genetic differences and longevity‐related phenotypes influence lifespan and lifespan variation in a sex‐specific manner in mice

Genetic differences and longevity‐related phenotypes influence lifespan and lifespan variation in a sex‐specific manner in mice

Age-related transcriptional modules and TF-miRNA-mRNA interactions in neonatal and infant human thymus

Senotherapeutic peptide reduces skin biological age and improves skin health markers

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