Unveiling the Anti-Aging Potential of 3HB: Lifespan Extension, Healthy Life Improvement, and Cellular Senescence Delay
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE262770 | GEO | 2025/06/04
REPOSITORIES: GEO
Similar Datasets
Project description:Unveiling the Anti-Aging Potential of 3HB: Lifespan Extension, Healthy Life Improvement, and Cellular Senescence Delay
| PRJNA1093150 | ENA
Project description:The SIRT1 deacetylase is one of the best-studied potential mediators of some of the anti-aging effects of calorie restriction (CR); but its role in CR-dependent lifespan extension has not been demonstrated. We previously found that mice lacking both copies of SIRT1 displayed a shorter median lifespan than wild type mice on an ad libitum diet. Here we report that median lifespan extension in CR heterozygote SIRT1+/- mice was identical (51%) to that observed in wild type mice but SIRT1+/- mice displayed a higher frequency of some certain pathologies. Although larger studies in different genetic backgrounds are necessary , these results provide strong initial evidence for the requirement of SIRT1 for the anti-aging effects of CR, but suggest that its high expression is not required for CR-induced lifespan extension. Key words: SIRT1, caloric restriction, lifespan, anti-aging 2-5 month old male mice of 3 different genotypes (SIRT1+/+, SIRT1+/-, and SIRT1-/-) that had normal, reduced or no expression of SIRT1 were treated with either a 40% caloric restricted diet (CR) or an ad libitum diet (AL). 2-4 replicates of each experimental condition were used in the analysis.
2014-04-25 | E-GEOD-46895 | biostudies-arrayexpress
Project description:The SIRT1 deacetylase is one of the best-studied potential mediators of some of the anti-aging effects of calorie restriction (CR); but its role in CR-dependent lifespan extension has not been demonstrated. We previously found that mice lacking both copies of SIRT1 displayed a shorter median lifespan than wild type mice on an ad libitum diet. Here we report that median lifespan extension in CR heterozygote SIRT1+/- mice was identical (51%) to that observed in wild type mice but SIRT1+/- mice displayed a higher frequency of some certain pathologies. Although larger studies in different genetic backgrounds are necessary , these results provide strong initial evidence for the requirement of SIRT1 for the anti-aging effects of CR, but suggest that its high expression is not required for CR-induced lifespan extension. Key words: SIRT1, caloric restriction, lifespan, anti-aging
2014-04-25 | GSE46895 | GEO
Project description:DNA repair-deficient Ercc1Δ/- mice show premature cell death, senescence and numerous accelerated aging features limiting lifespan to 4-6 month. Simultaneously they exhibit a ‘survival response’, which suppresses growth and enhances maintenance, resembling the anti-aging response induced by dietary restriction (DR). Here we report that subjecting these progeroid, dwarf mutants to actual dietary restriction (DR) resulted in the largest lifespan increase recorded in mammals. Thirty percent DR tripled median and maximal remaining lifespan, and drastically retarded numerous aspects of accelerated aging, e.g. DR animals retained 50% more neurons and maintained full motoric function. The DR response in Ercc1Δ/- mice resembled DR in wild type animals including reduced insulin signaling. Interestingly, ad libitum Ercc1Δ/- liver expression profiles showed preferential extinction of expression of long genes, consistent with genome-wide accumulation of stochastic, transcription-blocking lesions, which affect long genes more than short ones. DR largely prevented this decline of transcriptional output, indicating that DR prolongs genome function. Our findings strengthen the link between DNA damage and aging, establish Ercc1Δ/- mice as powerful model for identifying interventions to promote healthy aging, reveal untapped potential for reducing endogenous damage, provide new venues for understanding the molecular mechanism of DR, and suggest a counterintuitive DR-like therapy for human progeroid genome instability syndromes and DR-like interventions for preventing neurodegenerative diseases.
2016-09-09 | GSE77226 | GEO
Project description:DNA repair-deficient Ercc1Δ/- mice show premature cell death, senescence and numerous accelerated aging features limiting lifespan to 4-6 month. Simultaneously they exhibit a ‘survival response’, which suppresses growth and enhances maintenance, resembling the anti-aging response induced by dietary restriction (DR). Here we report that subjecting these progeroid, dwarf mutants to actual dietary restriction (DR) resulted in the largest lifespan increase recorded in mammals. Thirty percent DR tripled median and maximal remaining lifespan, and drastically retarded numerous aspects of accelerated aging, e.g. DR animals retained 50% more neurons and maintained full motoric function. The DR response in Ercc1Δ/- mice resembled DR in wild type animals including reduced insulin signaling. Interestingly, ad libitum Ercc1Δ/- liver expression profiles showed preferential extinction of expression of long genes, consistent with genome-wide accumulation of stochastic, transcription-blocking lesions, which affect long genes more than short ones. DR largely prevented this decline of transcriptional output, indicating that DR prolongs genome function. Our findings strengthen the link between DNA damage and aging, establish Ercc1Δ/- mice as powerful model for identifying interventions to promote healthy aging, reveal untapped potential for reducing endogenous damage, provide new venues for understanding the molecular mechanism of DR, and suggest a counterintuitive DR-like therapy for human progeroid genome instability syndromes and DR-like interventions for preventing neurodegenerative diseases.
2016-09-09 | GSE77321 | GEO
Project description:Neuroaging is one of the most distinct signs of aging, which promotes mild cognitive impairment (MCI) and various neurodegenerative diseases. Previous studies have indicated that Panax ginseng C. A. Mey. (ginseng) root polysaccharides have positive effects against senescence and nerve damage. However, its structure and role in delaying senescence-associated neuroaging have not been comprehensively studied. Therefore, this research characterized the structural features of a ginseng root polysaccharide (GRP-E1F2) and the potential mechanism underlying its anti-neurodegeneration effect against senescence-related function and pathological damage. GRP-E1F2 is a neutral polysaccharide with 11.688 kDa molecular weight, which was isolated from the ginseng roots. In this study, NMR, HPLC, FT-IR, and methylation analyses were performed to identify the physiochemical characteristics of GRP-E1F2, which provided its repetitive unit structures. The in vivo experiments revealed that GRP-E1F2 prolonged the lifespan and mitigated senescence-related symptoms including aggregation of lipofuscin and ROS, as well as the antioxidant enzyme inactivation in aging animals (C. elegans and mice). Furthermore, tert-butyl hydroperoxide (tBHP) induced senescent cells indicated that GRP-E1F2 treated has beneficial anti-aging effects. Moreover, the transgenic C. elegans expressing GFP in D-type gamma-aminobutyric acid (GABA)-positive neurons and mice indicated that GRP-E1F2 reduced neuronal morphological abnormalities and reversed aging-induced cognitive deficits, indicating the anti-neuroaging effects of GRP-E1F2. Mechanistically, GRP-E1F2 downregulates cellular senescence in aging brains and cell models, which was indicated by senescence-associated β-galactosidase (SA-β-gal) activity, marker protein p53, p21, phospho-histone H2A.X, and senescence-associated secretory phenotype (SASP). In addition, RNA-seq, RT-qPCR, and immunofluorescence assays revealed that GRP-E1F2 down-regulated mRNA and protein levels of prodynorphin (Pdyn) in aging models. Moreover, the p53 activator and overexpression vectors of Pdyn were employed to determine the pharmacological mechanism of GRP-E1F2 in reducing Pdyn expressions to delay neuroaging by inhibiting the cellular senescence signaling pathway. This research provides theoretical support and experimental evidence for the clinical application of ginseng root polysaccharides against senescence-associated neuroaging, promoting the modern development of traditional medicines from natural polysaccharides.
2025-08-31 | GSE274375 | GEO
Project description:Verlingue2016 - Signalling pathway that
control S-phase entry and geroconversion - Boolean Model
This model is described in the article:
A comprehensive approach to
the molecular determinants of lifespan using a Boolean model of
geroconversion.
Verlingue L, Dugourd A, Stoll G,
Barillot E, Calzone L, Londoño-Vallejo A.
Aging Cell 2016 Sep; :
Abstract:
Altered molecular responses to insulin and growth factors
(GF) are responsible for late-life shortening diseases such as
type-2 diabetes mellitus (T2DM) and cancers. We have built a
network of the signaling pathways that control S-phase entry
and a specific type of senescence called geroconversion. We
have translated this network into a Boolean model to study
possible cell phenotype outcomes under diverse molecular
signaling conditions. In the context of insulin resistance, the
model was able to reproduce the variations of the senescence
level observed in tissues related to T2DM's main morbidity and
mortality. Furthermore, by calibrating the pharmacodynamics of
mTOR inhibitors, we have been able to reproduce the
dose-dependent effect of rapamycin on liver degeneration and
lifespan expansion in wild-type and HER2-neu mice. Using the
model, we have finally performed an in silico prospective
screen of the risk-benefit ratio of rapamycin dosage for
healthy lifespan expansion strategies. We present here a
comprehensive prognostic and predictive systems biology tool
for human aging.
This model is hosted on
BioModels Database
and identified by:
MODEL1611180000.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2016-11-29 | MODEL1611180000 | BioModels
Project description:Introduction: Sensitive skin is characterized by skin barrier disruption which is usually prone to react to external stimuli including UV, air pollution as well as cosmetic allergens. Sensitive skin tends to react with oxidative stress factors that could further lead to skin inflammation resulting in inflamm-aging. But almost no inflamm-aging models for sensitive skin, so it is worth constructing a method to screen anti-inflammaging ingredients and products. Methods: An in-vitro macrophages-fibroblasts model was established to evaluate the anti-inflammaging effect of ingredients. M1 phenotype and aging-associated gene expression were recorded by qPCR test to validate the inflamm-aging model. RNA sequencing was used to further elaborate the inflamm-aging mechanism of two validated ingredients. Results and conclusion: A novel in-vitro model of sensitive skin inflamm-aging was constructed by applying M1 phenotype of THP-1 culture medium supernatant to introduce the cellular senescence of the fibroblast cells, which could be used to screen out anti-inflammaging ingredients. In this model, supramolecular bakuchiol could promote collagen COL1A1 and COL3A3 production and inhibit inflammatory factors by increasing anti-inflammatory gene transcription (PTX3, ADAM33, and PDLIM1), while Terminalia chebula extract can inhibit cell senescence by reducing transcription of MAP4K2, and inflammatory factors CCL3 accumulation.
2025-04-16 | GSE286316 | GEO
Project description:Various anti-aging interventions exhibit potential in extending lifespan, yet most of these interventions are inefficacy or even have deleterious effects on healthspan. Ginkgolide B (GB) is a Ginkgo biloba-derived small molecule that reduces aging-related morbidities; however, the effects of GB on healthspan and longevity remain elusive. Here, we report that continuous oral GB administration in mice starting at 20 months extended their lifespan by 20% and reduced tumour incidence. Besides, GB administration significantly improved healthspan evidenced by enhancement in muscle quality, physical performance, grip strength, metabolism, frailty index, systemic inflammation, and senescence. Moreover, GB administration ameliorated aging-related pathologies without any apparent adverse effects. Single-nucleus RNA sequencing (snRNA-seq) revealed that GB improved aging-associated abnormal cell-type composition, intracellular signalling pathways, and cell-cell communication in skeletal muscles. GB also reduced the levels of aging-induced novel Runx1+ type 2B myonuclei, which are associated with apoptotic burden and aging-related signatures. Runx1 derived senescence, as shown by gain- and loss-of-function assays. Together, a new function of GB in extending the healthspan in aging is identified, which contributes to lifespan extension. The senomorphic effects of GB on the multifactorial aging process may provide new prospects for achieving healthy aging and longevity extension.
2024-10-31 | GSE254739 | GEO
Project description:Senescence, a stable state of growth arrest, affects many physiological and pathophysiological processes, especially aging. Previous work has indicated that transcription factors (TFs) play a role in regulating senescence. However, a systematic study of regulatory TFs during replicative senescence (RS) using multi-omics analysis is still lacking. Here, we generated time-resolved RNA-seq, reduced representation bisulfite sequencing (RRBS) and ATAC-seq datasets during RS of mouse skin fibroblasts, which demonstrated that an enhanced inflammatory response and reduced proliferative capacity were the main characteristics of RS in both the transcriptome and epigenome. Through integrative analysis and genetic manipulation, we found that transcription factors E2F4, TEAD1 and AP-1 are key regulators of RS. Overexpression of E2f4 improved cellular proliferative capacity, attenuated SA-β-Gal activity and changed RS-associated differentially methylated sites (DMSs). Moreover, knockdown of Tead1 attenuated SA-β-Gal activity and partially altered the RS-associated transcriptome. In addition, knockdown of Atf3, one member of AP-1 superfamily TFs, reduced Cdkn2a (P16) expression in pre-senescent fibroblasts. Taken together, results of this study identified transcription factors regulating the senescence program through multi-omics analysis, providing potential therapeutic targets for anti-aging.
2021-10-08 | GSE185416 | GEO