Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Repeated intermittent clearance of p21-highly-expressing cells extends lifespan and confers sustained benefits to health and physical function

ABSTRACT: A key challenge in aging research is to extend lifespan in tandem with slowing down functional decline so that the life with good health (healthspan) can be extended. Here, we show that clearance of a small number of cells, which highly express p21Cip1 (p21high), starting from 20 months improves cardiac and metabolic function, and extends both median and maximum lifespan in mice. Importantly, by assessing health and physical function of these mice monthly until death, we show that clearance of p21high cells improves physical function at all remaining stages of life, suggesting morbidity compression and healthspan extension. Mechanistically, p21high cells encompass several cell types, with a conserved pro-inflammatory signature. Clearance of p21high cells reduces inflammation, and rejuvenates transcriptomic signatures of various tissues to younger states. These findings demonstrate the feasibility of morbidity compression in mice, and indicate p21high cells as a therapeutic target for healthy aging.

ORGANISM(S): Mus musculus

PROVIDER: GSE269660 | GEO | 2024/06/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Ginkgolide B increase healthspan and lifespan of female mice

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

Targeting NAT10 enhances healthspan and lifespan in a mouse model of human accelerated aging syndrome.

Project description:Targeting NAT10 enhances healthspan and lifespan in a mouse model of human accelerated aging syndrome.

2018-03-22 | E-MTAB-6578 | biostudies-arrayexpress

Improvements in health, not survival, by late-onset metformin treatment

Project description:The biguanide metformin improves health and survival in male mice; however, it is unclear whether metformin will confer health and lifespan benefits to mice when started late in life. Two year-old mice fed on standard chow were treated with 1% metformin every-other week (EOW) or two consecutive weeks per month (2WM). EOW mice displayed improvements in healthspan reminiscent of mice on caloric restriction. The age-associated histopathological changes in liver and kidney were significantly reduced in EOW compared to 2WM or control mice. Some of the affected gene transcripts and metabolites were found to be risk predictors of metabolic disorder. Neither EOW nor 2WM mice exhibited extension in mean or maximum lifespan compared with control animals. Thus, metformin supplementation had a strong impact on reversing some of the deleterious effects of aging and resulted in an improvement of health in old male mice in the absence of an extension of lifespan.

2018-02-23 | GSE97074 | GEO

Effect of methione restriction in the liver of WT and Lmna G609G KI mice

Project description:Dietary intervention constitutes a feasible approach for modulating metabolism and improving healthspan and lifespan. Methionine restriction (MR) delays the appearance of age-related diseases and increases longevity in normal mice. However, the effect of MR on premature aging remains to be elucidated. Here, we describe that MR extends lifespan in two different mouse models of Hutchinson-Gilford progeria syndrome (HGPS) by reversing the transcriptome alterations in inflammation and DNA-damage response genes present in this condition. Further, MR improves the lipid profile and alters the levels of bile acids, both in wild-type and in progeroid mice. Notably, treatment with the bile acid cholic acid improves healthspan and lifespan in vivo. These results suggest the existence of a metabolic pathway involved in the longevity extension achieved by MR and support the possibility of dietary interventions for treating progeria.

2018-08-27 | GSE117188 | GEO

Tomatidine enhances lifespan and healthspan in C. elegans through mitophagy induction via the SKN-1/Nrf2 pathway.

Project description:Aging is a major international concern and brings with it formidable socioeconomical and healthcare challenges. An attainable approach to improve general health in humans is using small molecules. Tomatidine, a natural compound abundant in unripe tomatoes, inhibits aging-related skeletal muscle atrophy in mice. Here we show that tomatidine extends lifespan and healthspan in the aging animal model C. elegans, which shares many major longevity pathways with those of mammals. Tomatidine improves behaviors related to healthspan, including increased pharyngeal pumping and swimming movement, and also reduces deterioration of muscle cells in worms. Microarray, imaging, and behavioral analysis reveal that tomatidine maintains mitochondrial homeostasis through mitochondrial biogenesis and PINK-1/DCT-1-dependent mitophagy. Mechanistically, tomatidine induces mitochondrial hormesis by mildly inducing ROS production, which in turn activates the cellular antioxidant response SKN-1/Nrf2 pathway, followed by increased mitophagy in worms, primary rat neurons, and human cells. Our data suggest that tomatidine may delay some physiological aspects of aging, and points to new approaches for pharmacological interventions towards diseases of aging.

2017-08-21 | GSE85237 | GEO

Lithium promotes longevity via GSK-3 and NRF-2 and is additive to other anti-aging interventions

Project description:The quest to extend healthspan via pharmacological means is becoming increasingly urgent, both from a health and economic perspective. Here we show that lithium, a drug approved for human use, promotes longevity and healthspan. We demonstrate that lithium extends lifespan in female and male Drosophila, when administered throughout adulthood or only later in life. The life-extending mechanism involves the inhibition of glycogen synthase kinase-3 (GSK-3) and activation of the transcription factor nuclear factor erythroid 2-related factor (NRF-2). Combining genetic loss of the NRF-2 repressor Kelch-like ECH-associated protein 1 (Keap1) with lithium treatment revealed that high levels of NRF-2 activation conferred stress resistance, while low levels additionally promoted longevity. The discovery of GSK-3 as a new therapeutic target for aging will likely lead to more effective treatments that can modulate mammalian aging and further improve health in later life. The microarray experiment examines the transcriptional profiles of wild-type (w1118) vs. wild-type (w1118) + Lithium (LiCl, 10mM). Heads and thoraces from once mated females treated with vehicle or 10mM Li were snap frozen after 10d of treatment. RNA was Dnase treated and checked for quality by Biorad Experion. RNA was processed to cRNA, labeled and used for microarray analysis (GeneChip Drosophila Genome 2.0 Array), following manufacturer's protocol.

2016-04-07 | E-MTAB-3809 | biostudies-arrayexpress

Mechanical stress through growth on stiffer substrates has only mild impacts on animal health and longevity in C. elegans

Project description:Mechanical stress is a measure of internal resistance exhibited by a body or material when external forces, such as compression, tension, bending, etc. are applied. The study of mechanical stress on health and aging is a continuously growing field, as major changes to the extracellular matrix and cell-to-cell adhesions can result in dramatic changes to tissue stiffness during aging and diseased conditions. For example, during normal aging, many tissues including the ovaries, skin, blood vessels, and heart exhibit increased stiffness, which can result in a significant reduction in function of that organ. As such, numerous model systems have recently emerged to study the impact of mechanical and physical stress on cell and tissue health, including cell-culture conditions with matrigels and other surfaces that alter substrate stiffness and ex vivo tissue models that can apply stress directly to organs like muscle or tendons. Here, we sought to develop a novel method in an in vivo, model organism setting to study the impact of mechanical stress on aging, by increasing substrate stiffness in solid agar medium of C. elegans. To our surprise, we found shockingly limited impact of growth of C. elegans on stiffer substrates, including limited effects on cellular health, gene expression, organismal health, stress resilience, and longevity. Overall, our studies reveal that altering substrate stiffness of growth medium for C. elegans have only mild impact on animal health and longevity; however, these impacts were not nominal and open up important considerations for C. elegans biologists in standardizing agar medium choice for experimental assays.

2024-04-05 | E-MTAB-13938 | biostudies-arrayexpress

Methylation arrays (MethylationEPIC) of peripheral whole blood samples from adults aged between 19-96 years

Project description:Epigenetic remodeling is central to understanding the molecular mechanisms that occur and drive human aging. In fact, DNA methylation clocks are capable of estimating biological age, which determines human lifespan and healthspan. Here, using Illumina's MethylationEPIC array technology, we have profiled the DNA methylation landscape of peripheral whole blood samples from adult individuals ranging in age from 19 to 96 years.

2024-09-29 | E-MTAB-13431 | biostudies-arrayexpress

SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass

Project description:Increased expression of SIRT1 extends the lifespan of lower organisms and delays the onset of age-related diseases in mammals. Here, we show that SRT2104, a synthetic small molecule activator of SIRT1, extends both mean and maximal lifespan of mice fed a standard diet. This is accompanied by improvements in health, including enhanced motor coordination, performance, bone mineral density and insulin sensitivity associated with higher mitochondrial content and decreased inflammation. Short-term SRT2104 treatment preserves bone and muscle mass in an experimental model of atrophy. These results demonstrate it is possible to design a small molecule that can slow aging and delay multiple age-related diseases in mammals, supporting the therapeutic potential of SIRT1 activators in humans. Key words: Sirtuins, lifespan, healthspan, osteoporosis, muscle wasting, inflammation

2014-09-22 | GSE49000 | GEO

Transplanting rejuvenated blood stem cells extends lifespan of aged immunocompromised mice [scRNA-seq of LSK cells]

Project description:One goal of regenerative medicine is to rejuvenate tissues and extend lifespan by restoring the function of endogenous aged stem cells. However, evidence that somatic stem cells can be targeted in vivo to extend lifespan is still lacking. Here, we demonstrate that after a short systemic treatment with a specific inhibitor of the small RhoGTPase Cdc42 (CASIN), transplanting aged hematopoietic stem cells (HSCs) from treated mice is sufficient to extend the healthspan and lifespan of aged immunocompromised mice without additional treatment. In detail, we show that systemic CASIN treatment improves strength and endurance of aged mice by increasing the myogenic regenerative potential of aged skeletal muscle stem cells. Further, we show that CASIN modifies niche localization and H4K16ac polarity of HSCs in vivo. Single cell profiling reveals changes in HSC transcriptome, which underlie enhanced lymphoid and regenerative capacity in serial transplantation assays. Overall, we provide proof-of-concept evidence that a short systemic treatment to decrease Cdc42 activity improves the regenerative capacity of different endogenous aged stem cells in vivo, and that rejuvenated HSCs exert a broad systemic effect sufficient to extend murine health- and lifespan.

2022-12-01 | GSE197070 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data