Aging & Longevity

Abalone peptide increases stress resilience and cost-free longevity via SKN-1-governed transcriptional metabolic reprogramming in C. elegans

1 week 3 days ago
A major goal of healthy aging is to prevent declining resilience and increasing frailty, which are associated with many chronic diseases and deterioration of stress response. Here, we propose a loss-or-gain survival model, represented by the ratio of cumulative stress span to life span, to quantify stress resilience at organismal level. As a proof of concept, this is demonstrated by reduced survival resilience in Caenorhabditis elegans exposed to exogenous oxidative stress induced by paraquat or...
Qiangqiang Wang

3,4-dimethoxychalcone induces autophagy and reduces neointimal hyperplasia and aortic lesions in mouse models of atherosclerosis

1 week 4 days ago
Autophagy inducers can prevent cardiovascular aging and age-associated diseases including atherosclerosis. Therefore, we hypothesized that autophagy-inducing compounds that act on atherosclerosis-relevant cells might have a protective role in the development of atherosclerosis. Here we identified 3,4-dimethoxychalcone (3,4-DC) as an inducer of autophagy in several cell lines from endothelial, myocardial and myeloid/macrophagic origin, as demonstrated by the aggregation of the autophagosome...
Giulia Cerrato

Indole produced during dysbiosis mediates host-microorganism chemical communication

1 week 4 days ago
An imbalance of the gut microbiota, termed dysbiosis, has a substantial impact on host physiology. However, the mechanism by which host deals with gut dysbiosis to maintain fitness remains largely unknown. In Caenorhabditis elegans, Escherichia coli, which is its bacterial diet, proliferates in its intestinal lumen during aging. Here, we demonstrate that progressive intestinal proliferation of E. coli activates the transcription factor DAF-16, which is required for maintenance of longevity and...
Rui-Qiu Yang

Multiomic analysis of cervical squamous cell carcinoma identifies cellular ecosystems with biological and clinical relevance

1 week 4 days ago
Cervical squamous cell carcinoma (CSCC) exhibits a limited response to immune-checkpoint blockade. Here we conducted a multiomic analysis encompassing single-cell RNA sequencing, spatial transcriptomics and spatial proteomics, combined with genetic and pharmacological perturbations to systematically develop a high-resolution and spatially resolved map of intratumoral expression heterogeneity in CSCC. Three tumor states (epithelial-cytokeratin, epithelial-immune (Epi-Imm) and epithelial...
Junpeng Fan

Age-related nitration/dysfunction of myogenic stem cell activator HGF

1 week 4 days ago
Mechanical perturbation triggers activation of resident myogenic stem cells to enter the cell cycle through a cascade of events including hepatocyte growth factor (HGF) release from its extracellular tethering and the subsequent presentation to signaling-receptor c-met. Here, we show that with aging, extracellular HGF undergoes tyrosine-residue (Y) nitration and loses c-met binding, thereby disturbing muscle homeostasis. Biochemical studies demonstrated that nitration/dysfunction is specific to...
Alaa Elgaabari

Against cortical reorganisation

1 week 4 days ago
Neurological insults, such as congenital blindness, deafness, amputation, and stroke, often result in surprising and impressive behavioural changes. Cortical reorganisation, which refers to preserved brain tissue taking on a new functional role, is often invoked to account for these behavioural changes. Here, we revisit many of the classical animal and patient cortical remapping studies that spawned this notion of reorganisation. We highlight empirical, methodological, and conceptual problems...
Tamar R Makin

Integrative multi-omics analysis reveals the critical role of the PBXIP1 gene in Alzheimer's disease

1 week 5 days ago
Alzheimer's disease (AD) is a neurodegenerative disorder, and its strongest risk factor is aging. A few studies have explored the relationship between aging and AD, while the underlying mechanism remains unclear. We assembled data across multi-omics (i.e., epigenetics, transcriptomics, and proteomics, based on frozen tissues from the dorsolateral prefrontal cortex) and neuropathological and clinical traits from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP). Aging was...
Jingyun Zhang

Repurposing nucleoside reverse transcriptase inhibitors (NRTIs) to slow aging

1 week 5 days ago
Repurposing drugs already approved in the clinic to be used off-label as geroprotectors, compounds that combat mechanisms of aging, are a promising way to rapidly reduce age-related disease incidence in society. Several recent studies have found that a class of drugs-nucleoside reverse transcriptase inhibitors (NRTIs)-originally developed as treatments for cancers and human immunodeficiency virus (HIV) infection, could be repurposed to slow the aging process. Interestingly, these studies propose...
Thomas Brochard

On the wake of metformin: Do anti-diabetic SGLT2 inhibitors exert anti-aging effects?

1 week 5 days ago
Here we propose that SGLT2 inhibitors (SGLT2i), a class of drugs primarily used to treat type 2 diabetes, could also be repositioned as anti-aging senomorphic drugs (agents that prevent the extrinsic harmful effects of senescent cells). As observed for metformin, another anti-diabetic drug with established anti-aging potential, increasing evidence suggests that SGLT2i can modulate some relevant pathways associated with the aging process, such as free radical production, cellular energy...
Lucia Scisciola

The vulnerability of aging states: A survival analysis across premodern societies

1 week 5 days ago
How states and great powers rise and fall is an intriguing enigma of human history. Are there any patterns? Do polities become more vulnerable over time as they age? We analyze longevity in hundreds of premodern states using survival analysis to help provide initial insights into these questions. This approach is commonly used to study the risk of death in biological organisms or failure in mechanical systems. The results reveal that the risk of state termination increased steeply over...
Marten Scheffer

CDC7 inhibition induces replication stress-mediated aneuploid cells with an inflammatory phenotype sensitizing tumors to immune checkpoint blockade

1 week 6 days ago
Serine/threonine kinase, cell division cycle 7 (CDC7) is critical for initiating DNA replication. TAK-931 is a specific CDC7 inhibitor, which is a next-generation replication stress (RS) inducer. This study preclinically investigates TAK-931 antitumor efficacy and immunity regulation. TAK-931 induce RS, generating senescence-like aneuploid cells, which highly expressed inflammatory cytokines and chemokines (senescence-associated secretory phenotype, SASP). In vivo multilayer-omics analyses in...
Tomoko Yamamori Morita

Unlocking the therapeutic potential of natural stilbene: Exploring pterostilbene as a powerful ally against aging and cognitive decline

2 weeks ago
The therapeutic potential of natural stilbenes, with a particular focus on pterostilbene (PTE), has emerged as a promising avenue of research targeting age-associated conditions encompassing cardiovascular diseases (CVD), diabetes mellitus (DM), and cognitive decline. This comprehensive investigation delves into the intricate mechanisms through which PTE, a polyphenolic compound abundant in grapes and blueberries, exerts its advantageous effects as an anti-aging agent. Central to its action is...
Bhaskar Jyoti Dutta

Chronic chromosome instability induced by Plk1 results in immune suppression in breast cancer

2 weeks ago
Chromosome instability (CIN) contributes to resistance to therapies and tumor evolution. Although natural killer (NK) cells can eliminate cells with complex karyotypes, high-CIN human tumors have an immunosuppressive phenotype. To understand which CIN-associated molecular features alter immune recognition during tumor evolution, we overexpress Polo-like kinase 1 (Plk1) in a Her2^(+) breast cancer model. These high-CIN tumors activate a senescence-associated secretory phenotype (SASP), upregulate...
Sridhar Kandala

GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21

2 weeks ago
As a major neuron type in the brain, the excitatory neuron (EN) regulates the lifespan in C. elegans. How the EN acquires senescence, however, is unknown. Here, we show that growth differentiation factor 11 (GDF11) is predominantly expressed in the EN in the adult mouse, marmoset and human brain. In mice, selective knock-out of GDF11 in the post-mitotic EN shapes the brain ageing-related transcriptional profile, induces EN senescence and hyperexcitability, prunes their dendrites, impedes their...
Di-Xian Wang

Genome homeostasis defects drive enlarged cells into senescence

2 weeks 1 day ago
Cellular senescence refers to an irreversible state of cell-cycle arrest and plays important roles in aging and cancer biology. Because senescence is associated with increased cell size, we used reversible cell-cycle arrests combined with growth rate modulation to study how excessive growth affects proliferation. We find that enlarged cells upregulate p21, which limits cell-cycle progression. Cells that re-enter the cell cycle encounter replication stress that is well tolerated in...
Sandhya Manohar

Oncogenic signals prime cancer cells for toxic cell overgrowth during a G1 cell cycle arrest

2 weeks 1 day ago
CDK4/6 inhibitors are remarkable anti-cancer drugs that can arrest tumor cells in G1 and induce their senescence while causing only relatively mild toxicities in healthy tissues. How they achieve this mechanistically is unclear. We show here that tumor cells are specifically vulnerable to CDK4/6 inhibition because during the G1 arrest, oncogenic signals drive toxic cell overgrowth. This overgrowth causes permanent cell cycle withdrawal by either preventing progression from G1 or inducing...
Reece Foy

CDK4/6 inhibitor-mediated cell overgrowth triggers osmotic and replication stress to promote senescence

2 weeks 1 day ago
Abnormal increases in cell size are associated with senescence and cell cycle exit. The mechanisms by which overgrowth primes cells to withdraw from the cell cycle remain unknown. We address this question using CDK4/6 inhibitors, which arrest cells in G0/G1 and are licensed to treat advanced HR+/HER2- breast cancer. We demonstrate that CDK4/6-inhibited cells overgrow during G0/G1, causing p38/p53/p21-dependent cell cycle withdrawal. Cell cycle withdrawal is triggered by biphasic p21 induction....
Lisa Crozier
4 hours 27 minutes ago
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