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Dual decline in gait and cognition as a high-risk clinical phenotype: differential associations with cerebral amyloid-<em>β</em> deposition and the apolipoprotein E ε4 allele and implications for integrated assessment

4 hours 29 minutes ago
CONCLUSION: The co-occurrence of slow gait and mild cognitive impairment (MCI-SG) represents a distinct high-risk clinical phenotype strongly linked to AD pathology. Aβ and APOE ε4 show differential associations across the gait-cognitive spectrum. Integrated assessment of gait and cognition improves risk stratification in older adults and may guide early intervention strategies.
Chenxi Ren

Methodological innovations in studying marginalized populations in research on neurodegeneration and ageing

4 hours 29 minutes ago
Underrepresented populations, often characterized by minority ethnicity, sex/gender or low socioeconomic status, have a higher risk burden and more adverse lifetime experiences of conditions negatively impacting cognitive health than better represented populations. There are several methodological challenges of research in and with marginalized populations that hinder research on improvements to their cognitive health. This review aims at presenting challenges of recruitment, data collection,...
Anja K Leist

Inactivation of V-ATPase induces autophagy and ectopic Notch activation to promote intestinal stem cell differentiation in adult <em>drosophila</em> midgut

4 hours 29 minutes ago
The self-renewal and differentiation of stem cells are tightly controlled to maintain tissue homeostasis. Failure in stem cell maintenance results in stem cell depletion and precocious aging. However, how stem cells are maintained still remains not fully understood. Here, through a large-scale RNAi screen for maintenance and proliferation of adult Drosophila intestinal stem cells (ISCs), we identify several subunits of V-ATPase including Vha68-2/ATP6V1A, required for ISC proliferation,...
Zhengran Li

Targeting chaperone-mediated autophagy by nutritional interventions mitigates age-related cardiac fibrosis and diastolic dysfunction

4 hours 29 minutes ago
Cardiac fibrosis, a major pathological hallmark of aging that leads to heart failure, is characterized by excessive collagen deposition. Our knowledge of what sustains collagen synthesis in the aging heart is still very preliminary. Here, we uncover a central role for chaperone-mediated autophagy (CMA), a selective lysosomal degradation pathway, in this process. We demonstrate that CMA is suppressed in the aging heart, which promotes collagen overproduction in fibroblasts, whereas enhancing CMA...
Ziwen Wang

Scientists find a simple way to stop cavities without drilling

1 day 1 hour ago
A liquid brushed onto cavities in seconds may spare many young children from pain, infection, and surgery. A major U.S. trial found that silver diamine fluoride stopped decay in more than half of treated baby teeth. The treatment requires no drilling, shots, or sedation, although it does permanently darken the decayed area.

Your gut may help your brain decide what to remember

1 day 2 hours ago
Signals traveling from the gut to the brain may help turn meals into lasting memories. Rats showed stronger memory activity after consuming nutritious foods, but not after drinking sweet liquids with little or no nutritional value. Blocking the vagus nerve erased this effect and made it harder for the animals to remember where food had been located. Over time, diets high in fat and sugar also weakened this memory system.

Mitochondrial accumulation and lysosomal dysfunction result in mitochondrial plaques in Alzheimer's disease

1 day 4 hours ago
Dysfunctional mitophagy is proposed as a key component of Alzheimer's disease (AD) pathology, yet direct in vivo evidence and mechanistic insights are still lacking. Here we show that AD model mice expressing a mitophagy reporter (APP/PSEN1/mt-Keima) develop large accumulation of acidic and neutral mitochondria within neuronal processes that form a previously unrecognized pathological structure termed mitochondrial plaques (MPs). The development of MPs is driven by abnormal mitochondrial buildup...
Xiuli Dan

CRISPR screens identify targets to rescue age-related T cell dysfunction in cancer

1 day 4 hours ago
Immune aging impairs T cell-mediated tumor control as well as cancer immunotherapy outcomes. The most important drivers of T cell dysfunction in aged tumors remain unknown. We performed single-cell CRISPR screens to identify Dusp5 and Zfp219 as key regulators of CD8^(+) T cell persistence and effector differentiation within aged tumors. Loss of Dusp5 increased extracellular signal-regulated kinase (ERK) phosphorylation and globally enhanced T cell proliferation. Conversely, Zfp219 deletion...
Alex C Y Chen

Restoring testosterone homeostasis: The therapeutic potential of stem Leydig cells for late-onset hypogonadism

1 day 4 hours ago
Late-Onset Hypogonadism (LOH), also known as male menopause syndrome, is a common health problem plaguing middle-aged and elderly men. Its core pathophysiological change lies in the progressive decline of testosterone levels in men with age. This leads to a series of symptoms involving sexual function, physical, and psychological aspects, seriously affecting the quality of life and overall health of patients. The core pathophysiological link of LOH lies in the progressive decline of testosterone...
Shenghan Xu

The role of ageing-specific PTM remodeling in myocardial ischemia-reperfusion injury

1 day 4 hours ago
Myocardial ischemia-reperfusion injury (MIRI) in patients with acute myocardial infarction (AMI) after thrombolytic therapy or percutaneous coronary intervention is one of the diseases with threatening health and increasing mortality. Despite decades of research, the precise mechanisms of MIRI remain incompletely understood. Ageing is considered one of the factors that exacerbate MIRI. Emerging evidence highlights that protein post‑translational modifications (PTMs) serve as critical regulators...
Qian Liu

Genomic, epigenomic and transcriptomic regulation of cellular senescence

1 day 4 hours ago
Cellular senescence is a complex, highly regulated cell state induced by cellular damage and stress. Senescence is central to many areas of biology, with roles in tumour suppression, tissue regeneration, antiviral defence and diverse age-related pathologies. Senescence is characterized by stable cell cycle arrest, metabolic alterations, chromatin remodelling and the secretion of pro-inflammatory and tissue-modifying factors that are collectively termed the senescence-associated secretory...
Rahagir Salekeen

Mitochondrial metabolism and epigenetic crosstalk drive SASP

1 day 4 hours ago
Senescent cells promote tissue dysfunction in part through the senescence-associated secretory phenotype (SASP)¹. Cytosolic mitochondrial nucleic acids activate innate immune signalling to initiate this inflammatory programme^(2,3). Here we show that mitochondrial metabolism provides a second layer of control that enables execution of the inflammatory programme. In senescent cells, the mitochondrial pyruvate-citrate-acetyl-CoA axis is upregulated, increasing the availability of acetyl-CoA to...
Hélène Martini

Senotypes define the diverse landscape of senescent cells

1 day 4 hours ago
Cellular senescence was initially defined in vitro as a stable cell-cycle arrest that occurs after repeated replication, but it is now recognized as a heterogeneous state shaped by cell type, species, senescence-inducing stress, tissue microenvironment and time. To organize this complexity, we propose the term 'senotype' to classify senescent cells by their inputs, molecular features and functional effects. We outline a practical framework incorporating: (1) cell identity and context; (2)...
Marissa J Schafer