Aging, Lifespan & Longevity

Lipofuscin causes atypical necroptosis through lysosomal membrane permeabilization

1 week 5 days ago
Lipofuscin granules enclose mixtures of cross-linked proteins and lipids in proportions that depend on the tissue analyzed. Retinal lipofuscin is unique in that it contains mostly lipids with very little proteins. However, retinal lipofuscin also presents biological and physicochemical characteristics indistinguishable from conventional granules, including indigestibility, tendency to cause lysosome swelling that results in rupture or defective functions, and ability to trigger NLRP3...
Chendong Pan

Genome-wide association studies of Arabidopsis dark-induced senescence reveals signatures of autophagy in metabolic reprogramming

1 week 5 days ago
Macroautophagy/autophagy is a conserved mechanism responsible for the degradation of unnecessary or dysfunctional components and recycling of the nutrients they contain in order to promote cellular or organismal longevity. In plants photosynthesis is massively impaired under extended darkness stress and the transition to heterotrophic metabolism results in carbon and nitrogen starvation which induces metabolic and autophagic shifts to recycle nutrients for plant survival. The majority of...
Feng Zhu

Adiponectin alleviated Alzheimer-like pathologies via autophagy-lysosomal activation

2 weeks ago
Adiponectin (APN) deficiency has also been associated with Alzheimer-like pathologies. Recent studies have illuminated the importance of APN signaling in reducing Aβ accumulation, and the Aβ elimination mechanism remains rudimentary. Therefore, we aimed to elucidate the APN role in reducing Aβ accumulation and its associated abnormalities by targeting autophagy and lysosomal protein changes. To assess, we performed a combined pharmacological and genetic approach while using preclinical models...
Kaiwu He

Nutritional reprogramming of mouse liver proteome is dampened by metformin, resveratrol, and rapamycin

2 weeks 2 days ago
Nutrient sensing pathways influence metabolic health and aging, offering the possibility that diet might be used therapeutically, alone or with drugs targeting these pathways. We used the Geometric Framework for Nutrition to study interactive and comparative effects of diet and drugs on the hepatic proteome in mice across 40 dietary treatments differing in macronutrient ratios, energy density, and drug treatment (metformin, rapamycin, resveratrol). There was a strong negative correlation between...
David G Le Couteur

Iron homeostasis and organismal aging

2 weeks 2 days ago
Iron is indispensable for normal body functions across species because of its critical roles in red blood cell function and many essential proteins and enzymes required for numerous physiological processes. Regulation of iron homeostasis is an intricate process involving multiple modulators at the systemic, cellular, and molecular levels. Interestingly, emerging evidence has demonstrated that many modulators of iron homeostasis contribute to organismal aging and longevity. On the other hand, the...
Rola S Zeidan

CENP-V is required for proper chromosome segregation through interaction with spindle microtubules in mouse oocytes

2 weeks 2 days ago
Proper chromosome segregation is essential to avoid aneuploidy, yet this process fails with increasing age in mammalian oocytes. Here we report a role for the scarcely described protein CENP-V in oocyte spindle formation and chromosome segregation. We show that depending on the oocyte maturation state, CENP-V localizes to centromeres, to microtubule organizing centers, and to spindle microtubules. We find that Cenp-V^(-/-) oocytes feature severe deficiencies, including metaphase I arrest,...
Dalileh Nabi

Necroptosis contributes to chronic inflammation and fibrosis in aging liver

2 weeks 3 days ago
Inflammaging, characterized by an increase in low-grade chronic inflammation with age, is a hallmark of aging and is strongly associated with various age-related diseases, including chronic liver disease (CLD) and hepatocellular carcinoma (HCC). Because necroptosis is a cell death pathway that induces inflammation through the release of DAMPs, we tested the hypothesis that age-associated increase in necroptosis contributes to chronic inflammation in aging liver. Phosphorylation of MLKL and MLKL...
Sabira Mohammed

The right time for senescence

2 weeks 4 days ago
Cellular senescence is a highly complex and programmed cellular state with diverse and, at times, conflicting physiological and pathological roles across the lifespan of an organism. Initially considered a cell culture artifact, senescence evolved from an age-related circumstance to an intricate cellular defense mechanism in response to stress, implicated in a wide spectrum of biological processes like tissue remodelling, injury and cancer. The development of new tools to study senescence in...
Diogo Paramos-de-Carvalho

Individual variations in 'brain age' relate to early-life factors more than to longitudinal brain change

2 weeks 4 days ago
Brain age is a widely used index for quantifying individuals' brain health as deviation from a normative brain aging trajectory. Higher-than-expected brain age is thought partially to reflect above-average rate of brain aging. Here, we explicitly tested this assumption in two independent large test datasets (UK Biobank [main] and Lifebrain [replication]; longitudinal observations ≈ 2750 and 4200) by assessing the relationship between cross-sectional and longitudinal estimates of brain age. Brain...
Didac Vidal-Pineiro

miR-125a-5p increases cellular DNA damage of aging males and perturbs stage-specific embryo development via Rbm38-p53 signaling

2 weeks 5 days ago
An increasing number of men are fathering children at an older age than in the past. While advanced maternal age has long been recognized as a risk factor for adverse reproductive outcomes, the influence of paternal age on reproduction is incompletely comprehended. Herein, we found that miR-125a-5p was upregulated in the sperm of aging males and was related to inferior sperm DNA integrity as an adverse predictor. Moreover, we demonstrated that miR-125a-5p suppressed mitochondrial function and...
Kuan Liang

Selective oxidative stress induces dual damage to telomeres and mitochondria in human T cells

2 weeks 5 days ago
Oxidative stress caused by excess reactive oxygen species (ROS) accelerates telomere erosion and mitochondrial injury, leading to impaired cellular functions and cell death. Whether oxidative stress-mediated telomere erosion induces mitochondrial injury, or vice versa, in human T cells-the major effectors of host adaptive immunity against infection and malignancy-is poorly understood due to the pleiotropic effects of ROS. Here we employed a novel chemoptogenetic tool that selectively produces a...
Ling Wang

Evolution of natural lifespan variation and molecular strategies of extended lifespan in yeast

2 weeks 5 days ago
To understand the genetic basis and selective forces acting on longevity, it is useful to examine lifespan variation among closely related species, or ecologically diverse isolates of the same species, within a controlled environment. In particular, this approach may lead to understanding mechanisms underlying natural variation in lifespan. Here, we analyzed 76 ecologically diverse wild yeast isolates and discovered a wide diversity of replicative lifespan (RLS). Phylogenetic analyses pointed to...
Alaattin Kaya

Mitochondrial dysfunction, oxidative stress, neuroinflammation, and metabolic alterations in the progression of Alzheimer's disease: A meta-analysis of in vivo magnetic resonance spectroscopy studies

2 weeks 5 days ago
Accumulating evidence demonstrates that metabolic changes in the brain associated with neuroinflammation, oxidative stress, and mitochondrial dysfunction play an important role in the pathophysiology of mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, the neural signatures associated with these metabolic alterations and underlying molecular mechanisms are still elusive. Accordingly, we reviewed the literature on in vivo human brain ¹H and ^(31)P-MRS studies and use...
Tao Song

Altered Chromatin States Drive Cryptic Transcription in Aging Mammalian Stem Cells

2 weeks 6 days ago
A repressive chromatin state featuring trimethylated lysine 36 on histone H3 (H3K36me3) and DNA methylation suppresses cryptic transcription in embryonic stem cells. Cryptic transcription is elevated with age in yeast and nematodes, and reducing it extends yeast lifespan, though whether this occurs in mammals is unknown. We show that cryptic transcription is elevated in aged mammalian stem cells, including murine hematopoietic stem cells (mHSCs) and neural stem cells (NSCs) and human mesenchymal...
Brenna S McCauley

Senescent cells suppress innate smooth muscle cell repair functions in atherosclerosis

2 weeks 6 days ago
Senescent cells (SNCs) degenerate the fibrous cap that normally prevents atherogenic plaque rupture, a leading cause of myocardial infarction and stroke. Here we explored the underlying mechanism using pharmacological or transgenic approaches to clear SNCs in the Ldlr ^(-/-) mouse model of atherosclerosis. SNC clearance reinforced fully deteriorated fibrous caps in highly advanced lesions, as evidenced by restored vascular smooth muscle cell (VSMC) numbers, elastin content, and overall cap...
Bennett G Childs

SARS-CoV-2, COVID-19 and the Ageing Immune System

2 weeks 6 days ago
The coronavirus disease 2019 (COVID-19) pandemic is a global health threat with particular risk for severe disease and death in older adults and in adults with age-related metabolic and cardiovascular disease. Recent advances in the science of ageing have highlighted how ageing pathways control not only lifespan but also healthspan, the healthy years of life. Here, we discuss the ageing immune system and its ability to respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We...
Juliet M Bartleson

The human telomeric proteome during telomere replication

2 weeks 6 days ago
Telomere shortening can cause detrimental diseases and contribute to aging. It occurs due to the end replication problem in cells lacking telomerase. Furthermore, recent studies revealed that telomere shortening can be attributed to difficulties of the semi-conservative DNA replication machinery to replicate the bulk of telomeric DNA repeats. To investigate telomere replication in a comprehensive manner, we develop QTIP-iPOND - Quantitative Telomeric chromatin Isolation Protocol followed by...
Chih-Yi Gabriela Lin

Evaluation of geriatric assessment and management on the toxic effects of cancer treatment (GAP70+): a cluster-randomised study

3 weeks 1 day ago
BACKGROUND: Older adults with advanced cancer are at a high risk for treatment toxic effects. Geriatric assessment evaluates ageing-related domains and guides management. We examined whether a geriatric assessment intervention can reduce serious toxic effects in older patients with advanced cancer who are receiving high risk treatment (eg, chemotherapy).
Supriya G Mohile
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