Aging, Lifespan & Longevity

Breakdown of specific functional brain networks in clinical variants of Alzheimer's disease

1 month 3 weeks ago
Alzheimer's disease (AD) is characterized by different clinical entities. Although AD phenotypes share a common molecular substrate (i.e., amyloid beta and tau accumulation), several clinicopathological differences exist. Brain functional networks might provide a macro-scale scaffolding to explain this heterogeneity. In this review, we summarize the evidence linking different large-scale functional network abnormalities to distinct AD phenotypes. Specifically, executive deficits in early-onset...
Lorenzo Pini

Advanced Maternal Age-associated SIRT1 Deficiency Compromises Trophoblast Epithelial-Mesenchymal Transition through an Increase in Vimentin Acetylation

1 month 3 weeks ago
Advanced maternal age (AMA) pregnancies are rapidly increasing and are associated with aberrant trophoblast cell function, poor placentation, and unfavorable pregnancy outcomes, presumably due to premature placental senescence. SIRT1 is an NAD^(+) -dependent deacetylase with well-known antiaging effects, but its connection with placental senescence is unreported. In this study, human term placentas and first-trimester villi were collected from AMA and normal pregnancies, and a mouse AMA model...
Liling Xiong

Roles and functions of antisense lncRNA in vascular aging

1 month 3 weeks ago
Vascular aging is a major cause of morbidity and mortality in the elderly population. Endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), forming the intima and media layers of the vessel wall respectively, are closely associated with the process of vascular aging and vascular aging-related diseases. Numerous studies have revealed the pathophysiologic mechanism through which lncRNA contributes to vascular aging, hence more attention is now paid to the role played by antisense long...
Xing-Yu Cui

Atlas of clinically distinct cell states and ecosystems across human solid tumors

1 month 3 weeks ago
Determining how cells vary with their local signaling environment and organize into distinct cellular communities is critical for understanding processes as diverse as development, aging, and cancer. Here we introduce EcoTyper, a machine learning framework for large-scale identification and validation of cell states and multicellular communities from bulk, single-cell, and spatially resolved gene expression data. When applied to 12 major cell lineages across 16 types of human carcinoma, EcoTyper...
Bogdan A Luca

Identification of distinct and age-dependent p16<sup>High</sup> microglia subtypes

1 month 3 weeks ago
Cells expressing high levels of the cyclin-dependent kinase (CDK)4/6 inhibitor p16 (p16^(High) ) accumulate in aging tissues and promote multiple age-related pathologies, including neurodegeneration. Here, we show that the number of p16^(High) cells is significantly increased in the central nervous system (CNS) of 2-year-old mice. Bulk RNAseq indicated that genes expressed by p16^(High) cells were associated with inflammation and phagocytosis. Single-cell RNAseq of brain cells indicated...
Nynke Talma

Ectopic cervical thymi and no thymic involution until midlife in naked mole rats

1 month 3 weeks ago
Immunosenescence is a hallmark of aging and manifests as increased susceptibility to infection, autoimmunity, and cancer in the elderly. One component of immunosenescence is thymic involution, age-associated shrinkage of the thymus, observed in all vertebrates studied to date. The naked mole rat (Heterocephalus glaber) has become an attractive animal model in aging research due to its extreme longevity and resistance to disease. Here, we show that naked mole rats display no thymic involution up...
Stephan Emmrich

Regeneration Roadmap: database resources for regenerative biology

1 month 4 weeks ago
Regeneration plays an instrumental role in biological development and damage repair by constructing and replacing cells, tissues, and organs. Since regenerative capacity declines with age, promoting regeneration is heralded as a potential strategy for delaying aging. On this premise, mechanisms that regulate regeneration have been extensively studied across species and in different tissues. However, an open and comprehensive database collecting and standardizing the abundant data generated in...
Wang Kang

Structure-based classification of tauopathies

1 month 4 weeks ago
The ordered assembly of tau protein into filaments characterizes several neurodegenerative diseases, which are called tauopathies. It was previously reported that, by cryo-electron microscopy, the structures of tau filaments from Alzheimer's disease^(1,2), Pick's disease³, chronic traumatic encephalopathy⁴ and corticobasal degeneration⁵ are distinct. Here we show that the structures of tau filaments from progressive supranuclear palsy (PSP) define a new three-layered fold. Moreover, the...
Yang Shi

Circadian autophagy drives iTRF-mediated longevity

1 month 4 weeks ago
Time-restricted feeding (TRF) has recently gained interest as a potential anti-ageing treatment for organisms from Drosophila to humans^(1-5). TRF restricts food intake to specific hours of the day. Because TRF controls the timing of feeding, rather than nutrient or caloric content, TRF has been hypothesized to depend on circadian-regulated functions; the underlying molecular mechanisms of its effects remain unclear. Here, to exploit the genetic tools and well-characterized ageing markers of...
Matt Ulgherait

Metabolism modulates network synchrony in the aging brain

1 month 4 weeks ago
Brain aging is associated with hypometabolism and global changes in functional connectivity. Using functional MRI (fMRI), we show that network synchrony, a collective property of brain activity, decreases with age. Applying quantitative methods from statistical physics, we provide a generative (Ising) model for these changes as a function of the average communication strength between brain regions. We find that older brains are closer to a critical point of this communication strength, in which...
Corey Weistuch

A genetic model of methionine restriction extends Drosophila health- and lifespan

1 month 4 weeks ago
Loss of metabolic homeostasis is a hallmark of aging and is characterized by dramatic metabolic reprogramming. To analyze how the fate of labeled methionine is altered during aging, we applied ^(13)C5-Methionine labeling to Drosophila and demonstrated significant changes in the activity of different branches of the methionine metabolism as flies age. We further tested whether targeted degradation of methionine metabolism components would "reset" methionine metabolism flux and extend the fly...
Andrey A Parkhitko

Identification of a small molecule SR9009 that activates NRF2 to counteract cellular senescence

1 month 4 weeks ago
The senescence-associated secretory phenotype (SASP) is a striking characteristic of senescence. Accumulation of SASP factors causes a pro-inflammatory response linked to chronic disease. Suppressing senescence and SASP represents a strategy to prevent or control senescence-associated diseases. Here, we identified a small molecule SR9009 as a potent SASP suppressor in therapy-induced senescence (TIS) and oncogene-induced senescence (OIS). The mechanism studies revealed that SR9009 inhibits the...
Li-Bin Gao

<em>APOE4</em> is associated with elevated blood lipids and lower levels of innate immune biomarkers in a tropical Amerindian subsistence population

1 month 4 weeks ago
In post-industrial settings, apolipoprotein E4 (APOE4) is associated with increased cardiovascular and neurological disease risk. However, the majority of human evolutionary history occurred in environments with higher pathogenic diversity and low cardiovascular risk. We hypothesize that in high-pathogen and energy-limited contexts, the APOE4 allele confers benefits by reducing innate inflammation when uninfected, while maintaining higher lipid levels that buffer costs of immune activation...
Angela R Garcia

Gut bacteria identified in colorectal cancer patients promote tumourigenesis via butyrate secretion

1 month 4 weeks ago
Emerging evidence is revealing that alterations in gut microbiota are associated with colorectal cancer (CRC). However, very little is currently known about whether and how gut microbiota alterations are causally associated with CRC development. Here we show that 12 faecal bacterial taxa are enriched in CRC patients in two independent cohort studies. Among them, 2 Porphyromonas species are capable of inducing cellular senescence, an oncogenic stress response, through the secretion of the...
Shintaro Okumura

Integrative proteome analysis implicates aberrant RNA splicing in impaired developmental potential of aged mouse oocytes

2 months ago
Aging has many effects on the female reproductive system, among which decreased oocyte quality and impaired embryo developmental potential are the most important factors affecting female fertility. However, the mechanisms underlying oocyte aging are not yet fully understood. Here, we selected normal reproductively aging female mice and constructed a protein expression profile of metaphase II (MII) oocytes from three age groups. A total of 187 differentially expressed (DE) proteins were...
Mingrui Li

China's low fertility may not hinder future prosperity

2 months ago
China's low fertility is often presented as a major factor which will hinder its prosperity in the medium to long term. This is based on the assumed negative consequences of an increasing old-age dependency ratio: a simplistic measure of relative changing age structures. Based on this view, policies to increase fertility are being proposed after decades of birth restriction policies. Here, we argue that a purely age structure-based reasoning which disregards labor force participation and...
Guillaume Marois
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