Aging & Longevity

Targeting CK2 eliminates senescent cells and prolongs lifespan in Zmpste24-deficient mice

2 weeks 2 days ago
Senescent cell clearance is emerging as a promising strategy for treating age-related diseases. Senolytics are small molecules that promote the clearance of senescent cells; however, senolytics are uncommon and their underlying mechanisms remain largely unknown. Here, we investigated whether genomic instability is a potential target for senolytic. We screened small-molecule kinase inhibitors involved in the DNA damage response (DDR) in Zmpste24^(-/-) mouse embryonic fibroblasts, a progeroid...
Jie Zhang

SGLT2 inhibition eliminates senescent cells and alleviates pathological aging

2 weeks 2 days ago
It has been reported that accumulation of senescent cells in various tissues contributes to pathological aging and that elimination of senescent cells (senolysis) improves age-associated pathologies. Here, we demonstrate that inhibition of sodium-glucose co-transporter 2 (SGLT2) enhances clearance of senescent cells, thereby ameliorating age-associated phenotypic changes. In a mouse model of dietary obesity, short-term treatment with the SGLT2 inhibitor canagliflozin reduced the senescence load...
Goro Katsuumi

Aging atlas reveals cell-type-specific effects of pro-longevity strategies

2 weeks 2 days ago
Organismal aging involves functional declines in both somatic and reproductive tissues. Multiple strategies have been discovered to extend lifespan across species. However, how age-related molecular changes differ among various tissues and how those lifespan-extending strategies slow tissue aging in distinct manners remain unclear. Here we generated the transcriptomic Cell Atlas of Worm Aging (CAWA, ) of wild-type and long-lived strains. We discovered cell-specific,...
Shihong Max Gao

Evolution of diapause in the African turquoise killifish by remodeling the ancient gene regulatory landscape

2 weeks 3 days ago
Suspended animation states allow organisms to survive extreme environments. The African turquoise killifish has evolved diapause as a form of suspended development to survive a complete drought. However, the mechanisms underlying the evolution of extreme survival states are unknown. To understand diapause evolution, we performed integrative multi-omics (gene expression, chromatin accessibility, and lipidomics) in the embryos of multiple killifish species. We find that diapause evolved by a...
Param Priya Singh

Identification of protein aggregates in the aging vertebrate brain with prion-like and phase-separation properties

2 weeks 3 days ago
Protein aggregation, which can sometimes spread in a prion-like manner, is a hallmark of neurodegenerative diseases. However, whether prion-like aggregates form during normal brain aging remains unknown. Here, we use quantitative proteomics in the African turquoise killifish to identify protein aggregates that accumulate in old vertebrate brains. These aggregates are enriched for prion-like RNA-binding proteins, notably the ATP-dependent RNA helicase DDX5. We validate that DDX5 forms...
Itamar Harel

Tissue-specific landscape of protein aggregation and quality control in an aging vertebrate

2 weeks 3 days ago
Protein aggregation is a hallmark of age-related neurodegeneration. Yet, aggregation during normal aging and in tissues other than the brain is poorly understood. Here, we leverage the African turquoise killifish to systematically profile protein aggregates in seven tissues of an aging vertebrate. Age-dependent aggregation is strikingly tissue specific and not simply driven by protein expression differences. Experimental interrogation in killifish and yeast, combined with machine learning,...
Yiwen R Chen

Combined inhibition of class 1-PI3K-alpha and delta isoforms causes senolysis by inducing p21(WAF1/CIP1) proteasomal degradation in senescent cells

2 weeks 3 days ago
The targeted elimination of radio- or chemotherapy-induced senescent cells by so-called senolytic substances represents a promising approach to reduce tumor relapse as well as therapeutic side effects such as fibrosis. We screened an in-house library of 178 substances derived from marine sponges, endophytic fungi, and higher plants, and determined their senolytic activities towards DNA damage-induced senescent HCT116 colon carcinoma cells. The Pan-PI3K-inhibitor wortmannin and its clinical...
Judith Neuwahl

Low-temperature strain-free encapsulation for perovskite solar cells and modules passing multifaceted accelerated ageing tests

2 weeks 3 days ago
Perovskite solar cells promise to be part of the future portfolio of photovoltaic technologies, but their instability is slow down their commercialization. Major stability assessments have been recently achieved but reliable accelerated ageing tests on beyond small-area cells are still poor. Here, we report an industrial encapsulation process based on the lamination of highly viscoelastic semi-solid/highly viscous liquid adhesive atop the perovskite solar cells and modules. Our encapsulant...
Paolo Mariani

Rejuvenation of peripheral immune cells attenuates Alzheimer's disease-like pathologies and behavioral deficits in a mouse model

2 weeks 3 days ago
Immunosenescence contributes to systematic aging and plays a role in the pathogenesis of Alzheimer's disease (AD). Therefore, the objective of this study was to investigate the potential of immune rejuvenation as a therapeutic strategy for AD. To achieve this, the immune systems of aged APP/PS1 mice were rejuvenated through young bone marrow transplantation (BMT). Single-cell RNA sequencing revealed that young BMT restored the expression of aging- and AD-related genes in multiple cell types...
Pu-Yang Sun

Maternal age is related to offspring DNA methylation: A meta-analysis of results from the PACE consortium

2 weeks 3 days ago
Worldwide trends to delay childbearing have increased parental ages at birth. Older parental age may harm offspring health, but mechanisms remain unclear. Alterations in offspring DNA methylation (DNAm) patterns could play a role as aging has been associated with methylation changes in gametes of older individuals. We meta-analyzed epigenome-wide associations of parental age with offspring blood DNAm of over 9500 newborns and 2000 children (5-10 years old) from the Pregnancy and Childhood...
Edwina Yeung

Unveiling ceramide dynamics: Shedding light on healthy aging in growth hormone-releasing hormone knockout mice

2 weeks 3 days ago
Dysregulation of growth hormone (GH) signaling consistently leads to increased lifespan in laboratory rodents, yet the precise mechanisms driving this extension remain unclear. Understanding the molecular underpinnings of the beneficial effects associated with GH deficiency could unveil novel therapeutic targets for promoting healthy aging and longevity. In our pursuit of identifying metabolites implicated in aging, we conducted an unbiased lipidomic analysis of serum samples from growth...
Alexander Tate Lasher

Gut microbiome remodeling and metabolomic profile improves in response to protein pacing with intermittent fasting versus continuous caloric restriction

2 weeks 4 days ago
The gut microbiome (GM) modulates body weight/composition and gastrointestinal functioning; therefore, approaches targeting resident gut microbes have attracted considerable interest. Intermittent fasting (IF) and protein pacing (P) regimens are effective in facilitating weight loss (WL) and enhancing body composition. However, the interrelationships between IF- and P-induced WL and the GM are unknown. The current randomized controlled study describes distinct fecal microbial and plasma...
Alex E Mohr

Cell-type-specific consequences of mosaic structural variants in hematopoietic stem and progenitor cells

2 weeks 4 days ago
The functional impact and cellular context of mosaic structural variants (mSVs) in normal tissues is understudied. Utilizing Strand-seq, we sequenced 1,133 single-cell genomes from 19 human donors of increasing age, and discovered the heterogeneous mSV landscapes of hematopoietic stem and progenitor cells. While mSVs are continuously acquired throughout life, expanded subclones in our cohort are confined to individuals >60. Cells already harboring mSVs are more likely to acquire additional...
Karen Grimes

Sch9(S6K) controls DNA repair and DNA damage response efficiency in aging cells

2 weeks 4 days ago
Survival from UV-induced DNA lesions relies on nucleotide excision repair (NER) and the Mec1^(ATR) DNA damage response (DDR). We study DDR and NER in aging cells and find that old cells struggle to repair DNA and activate Mec1^(ATR). We employ pharmacological and genetic approaches to rescue DDR and NER during aging. Conditions activating Snf1^(AMPK) rescue DDR functionality, but not NER, while inhibition of the TORC1-Sch9^(S6K) axis restores NER and enhances DDR by tuning PP2A activity,...
Chiara Lucca

Cbfβ regulates Wnt/β-catenin, Hippo/Yap, and Tgfβ signaling pathways in articular cartilage homeostasis and protects from ACLT surgery-induced osteoarthritis

2 weeks 4 days ago
As the most common degenerative joint disease, osteoarthritis (OA) contributes significantly to pain and disability during aging. Several genes of interest involved in articular cartilage damage in OA have been identified. However, the direct causes of OA are poorly understood. Evaluating the public human RNA-seq dataset showed that CBFB (subunit of a heterodimeric Cbfβ/Runx1, Runx2, or Runx3 complex) expression is decreased in the cartilage of patients with OA. Here, we found that the...
Wei Chen

Long-term demyelination and aging-associated changes in mice corpus callosum; evidence for the role of accelerated aging in remyelination failure in a mouse model of multiple sclerosis

2 weeks 4 days ago
Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disorder affecting the central nervous system. Evidence suggests that age-related neurodegeneration contributes to disability progression during the chronic stages of MS. Aging is characterized by decreased regeneration potential and impaired myelin repair in the brain. It is hypothesized that accelerated cellular aging contributes to the functional decline associated with neurodegenerative diseases. We assessed the impact of...
Elham Parandavar

Development and characterization of phospho-ubiquitin antibodies to monitor PINK1-PRKN signaling in cells and tissue

2 weeks 5 days ago
The selective removal of dysfunctional mitochondria, a process termed mitophagy, is critical for cellular health and impairments have been linked to aging, Parkinson disease, and other neurodegenerative conditions. A central mitophagy pathway is orchestrated by the ubiquitin (Ub) kinase PINK1 together with the E3 Ub ligase PRKN/Parkin. The decoration of damaged mitochondrial domains with phosphorylated Ub (p-S65-Ub) mediates their elimination though the autophagy system. As such p-S65-Ub has...
Jens O Watzlawik
5 hours 33 minutes ago
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