Aging & Longevity

Aneuploidy-induced cellular behaviors: Insights from Drosophila

2 months 1 week ago
A balanced gene complement is crucial for proper cell function. Aneuploidy, the condition of having an imbalanced chromosome set, alters the stoichiometry of gene copy numbers and protein complexes and has dramatic consequences at the cellular and organismal levels. In humans, aneuploidy is associated with different pathological conditions including cancer, microcephaly, mental retardation, miscarriages, and aging. Over the last century, Drosophila has provided a valuable system for studying the...
Jery Joy

Senolytics: from pharmacological inhibitors to immunotherapies, a promising future for patients' treatment

2 months 1 week ago
The involvement of cellular senescence in the initiation and propagation of diseases is clearly characterized, making the elimination of senescent cells essential to treat age-related diseases. The development of senolytic drugs demonstrated that targeting these cells limits the deterioration of patients' condition, by inducing apoptosis. Nevertheless, the first generations of senolytics which has been developed displayed their activities through specific mechanisms and demonstrated several...
V Lelarge

Petal abscission is promoted by jasmonic acid-induced autophagy at Arabidopsis petal bases

2 months 1 week ago
In angiosperms, the transition from floral-organ maintenance to abscission determines reproductive success and seed dispersion. For petal abscission, cell-fate decisions specifically at the petal-cell base are more important than organ-level senescence or cell death in petals. However, how this transition is regulated remains unclear. Here, we identify a jasmonic acid (JA)-regulated chromatin-state switch at the base of Arabidopsis petals that directs local cell-fate determination via autophagy....
Yuki Furuta

Therapeutic targeting of cellular senescence in diabetic macular edema: preclinical and phase 1 trial results

2 months 1 week ago
Compromised vascular endothelial barrier function is a salient feature of diabetic complications such as sight-threatening diabetic macular edema (DME). Current standards of care for DME manage aspects of the disease, but require frequent intravitreal administration and are poorly effective in large subsets of patients. Here we provide evidence that an elevated burden of senescent cells in the retina triggers cardinal features of DME pathology and conduct an initial test of senolytic therapy in...
Sergio Crespo-Garcia

Age-, sex- and proximal-distal-resolved multi-omics identifies regulators of intestinal aging in non-human primates

2 months 1 week ago
The incidence of intestinal diseases increases with age, yet the mechanisms governing gut aging and its link to diseases, such as colorectal cancer (CRC), remain elusive. In this study, while considering age, sex and proximal-distal variations, we used a multi-omics approach in non-human primates (Macaca fascicularis) to shed light on the heterogeneity of intestinal aging and identify potential regulators of gut aging. We explored the roles of several regulators, including those from tryptophan...
Xinyuan Wang

Older adults preserve audiovisual integration through enhanced cortical activations, not by recruiting new regions

2 months 1 week ago
Effective interactions with the environment rely on the integration of multisensory signals: Our brains must efficiently combine signals that share a common source, and segregate those that do not. Healthy ageing can change or impair this process. This functional magnetic resonance imaging study assessed the neural mechanisms underlying age differences in the integration of auditory and visual spatial cues. Participants were presented with synchronous audiovisual signals at various degrees of...
Samuel A Jones

Unzipped genome assemblies of polyploid root-knot nematodes reveal unusual and clade-specific telomeric repeats

2 months 1 week ago
Using long-read sequencing, we assembled and unzipped the polyploid genomes of Meloidogyne incognita, M. javanica and M. arenaria, three of the most devastating plant-parasitic nematodes. We found the canonical nematode telomeric repeat to be missing in these and other Meloidogyne genomes. In addition, we find no evidence for the enzyme telomerase or for orthologs of C. elegans telomere-associated proteins, suggesting alternative lengthening of telomeres. Instead, analyzing our assembled...
Ana Paula Zotta Mota

Transport mechanism of human bilirubin transporter ABCC2 tuned by the inter-module regulatory domain

2 months 1 week ago
Bilirubin is mainly generated from the breakdown of heme when red blood cells reach the end of their lifespan. Accumulation of bilirubin in human body usually leads to various disorders, including jaundice and liver disease. Bilirubin is conjugated in hepatocytes and excreted to bile duct via the ATP-binding cassette transporter ABCC2, dysfunction of which would lead to Dubin-Johnson syndrome. Here we determine the structures of ABCC2 in the apo, substrate-bound and ATP/ADP-bound forms using the...
Yao-Xu Mao

Short-term periodic restricted feeding elicits metabolome-microbiome signatures with sex dimorphic persistence in primate intervention

2 months 1 week ago
Dietary restriction has shown benefits in physiological, metabolic, and molecular signatures associated with aging but is a difficult lifestyle to maintain for most individuals. In mice, a less restrictive diet that allows for cyclical periods of reduced calories mitigates aging phenotypes, yet the effects of such an intervention in a genetically heterogenous, higher-order mammal has not been examined. Here, using middle-aged rhesus macaques matched for age and sex, we show that a regimen of 4...
Hagai Yanai

Ancient trees are essential elements for high-mountain forest conservation: Linking the longevity of trees to their ecological function

2 months 1 week ago
Mature forests and their extremely old trees are rare and threatened ancient vestiges in remote European high-mountain regions. Here, we analyze the role that extremely long-living trees have in mature forests biodiversity in relation to their singular traits underlying longevity. Tree size and age determine relative growth rates, bud abortion, and the water status of long-living trees. The oldest trees suffer indefectible age-related constraints but possess singular evolutionary traits defined...
Ot Pasques

Senescent cells and macrophages cooperate through a multi-kinase signaling network to promote intestinal transformation in Drosophila

2 months 1 week ago
Cellular senescence is a conserved biological process that plays a crucial and context-dependent role in cancer. The highly heterogeneous and dynamic nature of senescent cells and their small numbers in tissues make in vivo mechanistic studies of senescence challenging. As a result, how multiple senescence-inducing signals are integrated in vivo to drive senescence in only a small number of cells is unclear. Here, we identify cells that exhibit multiple features of senescence in a Drosophila...
Ishwaree Datta

Pharmacological interventions in human aging

2 months 1 week ago
Pharmacological interventions are emerging as potential avenues of alleviating age-related disease. However, the knowledge of ongoing clinical trials as they relate to aging and pharmacological interventions is dispersed across a variety of mediums. In this review we summarize 136 age-related clinical trials that have been completed or are ongoing. Furthermore, we establish a database that describe the trials (AgingDB, www.agingdb.com) keeping track of the previous and ongoing clinical trials,...
Michael Angelo Petr

ANKRD1 is a mesenchymal-specific driver of cancer-associated fibroblast activation bridging androgen receptor loss to AP-1 activation

2 months 1 week ago
There are significant commonalities among several pathologies involving fibroblasts, ranging from auto-immune diseases to fibrosis and cancer. Early steps in cancer development and progression are closely linked to fibroblast senescence and transformation into tumor-promoting cancer-associated fibroblasts (CAFs), suppressed by the androgen receptor (AR). Here, we identify ANKRD1 as a mesenchymal-specific transcriptional coregulator under direct AR negative control in human dermal fibroblasts...
Luigi Mazzeo

Detection of senescence using machine learning algorithms based on nuclear features

2 months 1 week ago
Cellular senescence is a stress response with broad pathophysiological implications. Senotherapies can induce senescence to treat cancer or eliminate senescent cells to ameliorate ageing and age-related pathologies. However, the success of senotherapies is limited by the lack of reliable ways to identify senescence. Here, we use nuclear morphology features of senescent cells to devise machine-learning classifiers that accurately predict senescence induced by diverse stressors in different cell...
Imanol Duran

Unraveling the brain's response to COVID-19: How SARS-CoV-2 afflicts dopaminergic neurons

2 months 1 week ago
COVID-19 patients often display dysfunctions of the nervous system, indicating an effect of SARS-CoV-2 on neural cells. Yang et al. now show that human stem-cell-derived dopaminergic neurons are susceptible to SARS-CoV-2, triggering inflammation and senescence. The study further identifies three FDA-approved drugs capable of reversing these cellular phenotypes.
Ilse Eidhof

Breaking the links between ageism and health: An integrated perspective

2 months 1 week ago
Ageism refers to prejudice, stereotypes or discrimination based on a person's actual or perceived chronological age. While ageism can affect people at all stages of the human lifespan, ageism against older adults has emerged as the most pervasive and potentially harmful. Much is now understood about how ageism can impact older people's health and wellbeing via structural, organisational, and provider level biases that threaten the provision of equitable and ethical healthcare. Negative attitudes...
Julie D Henry

Optimizing potassium polysulfides for high performance potassium-sulfur batteries

2 months 1 week ago
Potassium-sulfur batteries attract tremendous attention as high-energy and low-cost energy storage system, but achieving high utilization and long-term cycling of sulfur remains challenging. Here we show a strategy of optimizing potassium polysulfides for building high-performance potassium-sulfur batteries. We design the composite of tungsten single atom and tungsten carbide possessing potassium polysulfide migration/conversion bi-functionality by theoretical screening. We create two ligand...
Wanqing Song
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