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The activation of microglia by the complement system in neurodegenerative diseases

2 weeks ago
Neurodegenerative diseases (NDDs) are a group of neurological disorders characterized by the progressive loss of neuronal structure and function, leading to cognitive and behavioral impairments. Despite significant research advancements, there is currently no definitive cure for NDDs. With global aging on the rise, the burden of these diseases is becoming increasingly severe, highlighting the urgency of understanding their pathogenesis and developing effective therapeutic strategies. Microglia,...
He Zhao

Betaine and aging: A narrative review of findings, possible mechanisms, research perspectives, and practical recommendations

2 weeks ago
The rapid aging of the global population necessitates addressing age-related conditions through innovative strategies. Nutritional supplements have emerged as potential interventions for preventing or slowing age-related changes, with betaine being a promising candidate. This systematic review aims to provide a comprehensive analysis of current literature on the impact of betaine on the aging process. Specifically, we summarize the mechanisms through which betaine is proposed to affect aging, we...
Emilia Zawieja

Microglia degrade Alzheimer's amyloid-beta deposits extracellularly via digestive exophagy

2 weeks 1 day ago
How microglia digest Alzheimer's fibrillar amyloid-beta (Aβ) plaques that are too large to be phagocytosed is not well understood. Here, we show that primary microglial cells create acidic extracellular compartments, lysosomal synapses, on model plaques and digest them with exocytosed lysosomal enzymes. This mechanism, called digestive exophagy, is confirmed by electron microscopy in 5xFAD mouse brains, which shows that a lysosomal enzyme, acid phosphatase, is secreted toward the plaques in...
Rudy G Jacquet

Polyploid superficial uroepithelial bladder barrier cells express features of cellular senescence across the lifespan and are insensitive to senolytics

2 weeks 1 day ago
Lower urinary tract dysfunction (LUTD) increases with aging. Ensuing symptoms including incontinence greatly impact quality of life, isolation, depression, and nursing home admission. The aging bladder is hypothesized to be central to this decline, however, it remains difficult to pinpoint a singular strong driver of aging-related bladder dysfunction. Many molecular and cellular changes occur with aging, contributing to decreased resilience to internal and external stressors, affecting urinary...
Iman M Al-Naggar

GDF-15 as a proxy for epigenetic aging: associations with biological age markers, and physical function

2 weeks 1 day ago
Growth differentiation factor 15 (GDF-15) has emerged as a significant biomarker of aging, linked to various physiological and pathological processes. This study investigates circulating GDF-15 levels in a cohort of healthy individuals from the Balearic Islands, exploring its associations with biological age markers, including multiple DNA methylation (DNAm) clocks, physical performance, and other age-related biomarkers. Seventy-two participants were assessed for general health, body...
Margalida Torrens-Mas

Identification of differentially expressed miRNAs involved in vascular aging reveals pathways associated with the endocrine hormone regulation

2 weeks 1 day ago
Vascular aging refers to a series of processes where the elasticity of blood vessels diminishes, leading to stiffening, and deposition of fat components on the vessel walls, causing inflammation. Cardiovascular diseases, such as stroke and hypertension, play significant roles in morbidity and mortality rates among the elderly population. In this study, the Reactive Hyperemia Index (RHI) was measured to assess vascular endothelial function and aging-induced pathogenesis of vascular diseases in...
Jeongwon Jeon

Nobiletin-rich kososan, a Kampo formula, prevents the onset of apathy-like behavior and neuroinflammation in sickness behavior mouse model induced by increasing doses of lipopolysaccharide

2 weeks 1 day ago
Infectious diseases are often concomitant with symptoms of lassitude and emotional disturbances, including depression, the so-called sickness behavior. Kososan, a Kampo (traditional Japanese herbal) formula, has been clinically used for depressive mood, with demonstrated efficacy in stress-induced depressive-like behavior mouse models. Additionally, our previous study has shown that nobiletin-rich kososan (NKS) prevents aging-related depressive-like behaviors and neuroinflammation in mice. Here,...
Naoki Ito

Brain reboot: Enhancing neurogenesis and resilience

2 weeks 2 days ago
In this issue of Cell Stem Cell, Shen et al. investigate in vivo transient expression of Yamanaka factors (YFs) during embryogenesis and an adult mouse model of Alzheimer's disease (AD)-associated amyloidosis. These studies demonstrate that transient induction of YFs may be capable of enhancing neurogenesis and offer resilience against neurodegeneration.
David F Butler

Mapping the microRNA landscape in the older adult brain and its genetic contribution to neuropsychiatric conditions

2 weeks 2 days ago
MicroRNAs (miRNAs) play a crucial role in regulating gene expression and influence many biological processes. Despite their importance, understanding of how genetic variation affects miRNA expression in the brain and how this relates to brain disorders remains limited. Here we investigated these questions by identifying microRNA expression quantitative trait loci (miR-QTLs), or genetic variants associated with brain miRNA levels, using genome-wide small RNA sequencing profiles from dorsolateral...
Selina M Vattathil

Hallmarks of aging: A user's guide for comparative biologists

2 weeks 2 days ago
Since the first description of a set of characteristics of aging as so-called hallmarks or pillars in 2013/2014, these characteristics have served as guideposts for the research in aging biology. They have been examined in a range of contexts, across tissues, in response to disease conditions or environmental factors, and served as a benchmark for various anti-aging interventions. While the hallmarks of aging were intended to capture generalizable characteristics of aging, they are derived...
Peggy R Biga

Ergothioneine-rich Lentinula edodes mushroom extract restores mitochondrial functions in senescent HT22 cells

2 weeks 2 days ago
A decline in mitochondrial functions associated with ageing is the key factor of free radical generation which contributes to age-related pathologies. Protecting healthy functional mitochondrial networks with antioxidants is critical in promoting healthy ageing. This study aimed to investigate the protective effect of ergothioneine (EGT)-rich Lentinula edodes extract (LE-ETH) against tert-butyl hydroperoxide (t-BHP) assaulted senescent HT22 cells. Mitochondrial function was evaluated by...
Yasaaswini Apparoo

Receiving financial support and its association with late-age depression: The mediating role of social engagement

2 weeks 2 days ago
CONCLUSION: The study advances that although financial support plays a significant role in reducing depressive symptoms in older adults, social engagement also serves as an important mediator in this relationship. Enhancing opportunities for social engagement may amplify the protective effects of financial support, offering a more comprehensive approach to addressing mental health challenges among aging populations in India.
Keying Song

Spermidine alleviates thymopoiesis defects and aging of the peripheral T-cell population in mice after radiation exposure

2 weeks 2 days ago
The T cell aging process can be modified by genotoxic factors, including ionizing radiation, and metabolic controls, such as caloric restriction; the former accelerates and the latter retards the process. However, the mechanisms by which these systemic factors interact to cause T cell aging remain unclear. This study investigated the naïve T-cell pool, thymic cellularity, and transcriptome in mice irradiated with 3.8 Gy at 5 weeks of age and treated 13 months later with 30 mM spermidine (SPD), a...
Kengo Yoshida

GDF15/MIC-1: a stress-induced immunosuppressive factor which promotes the aging process

2 weeks 2 days ago
The GDF15 protein, a member of the TGF-β superfamily, is a stress-induced multifunctional protein with many of its functions associated with the regulation of the immune system. GDF15 signaling provides a defence against the excessive inflammation induced by diverse stresses and tissue injuries. Given that the aging process is associated with a low-grade inflammatory state, called inflammaging, it is not surprising that the expression of GDF15 gradually increases with aging. In fact, the GDF15...
Antero Salminen

Association of serum metabolites with frailty phenotype and its components: a cross-sectional case-control study

2 weeks 2 days ago
New insights into the metabolic mechanisms of frailty are needed. This study aimed to identify serum metabolites linked to frailty phenotype and its component through gas chromatography-mass spectrometry metabolomic analysis among community-dwelling older individuals. An exploratory, cross-sectional case-control study. Setting and participants: The participants were recruited from the ''Otassha Study,'' a cohort study conducted in Itabashi Ward, Tokyo, targeting women aged 65 years and older....
Takashi Shida

Reactive oxygen species control protein degradation at the mitochondrial import gate

2 weeks 2 days ago
While reactive oxygen species (ROS) have long been known to drive aging and neurodegeneration, their persistent depletion below basal levels also disrupts organismal function. Cells counteract loss of basal ROS via the reductive stress response, but the identity and biochemical activity of ROS sensed by this pathway remain unknown. Here, we show that the central enzyme of the reductive stress response, the E3 ligase Cullin 2-FEM1 homolog B (CUL2^(FEM1B)), specifically acts at mitochondrial TOM...
Rachael McMinimy