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The therapeutic potential of early exercise in Alzheimer's disease: Focus on the brain-spleen axis

1 day 4 hours ago
Alzheimer's disease (AD) is the predominant cause of cognitive dysfunction, with global prevalence increasing annually. AD progression is principally driven by the accumulation of amyloid-β (Aβ) and hyperphosphorylated microtubule-associated protein tau (p-Tau), which trigger a subsequent cascade of neuroinflammatory responses within the central nervous system (CNS). This pathological cascade is regulated by reciprocal CNS-peripheral immune crosstalk. The brain-spleen axis has emerged as a...
Tao Wang

Laminar organization of pyramidal neuron cell types defines distinct CA1 hippocampal subregions

1 day 4 hours ago
Investigating the cell type organization of hippocampal CA1 is essential for understanding its role in memory and cognition and its susceptibility to neurological disorders like Alzheimer's disease and epilepsy. Multiple studies have identified different organizational principles for gene expression and how it reflects cell types within the CA1 pyramidal layer including gradients or mosaic. Here, we identify sublaminar gene expression patterns within the mouse CA1 pyramidal layer that span...
Maricarmen Pachicano

27-Hydroxycholesterol triggers microglial senescence subsequent to iron over-loading contributes to brain aging, suppressed by Deferoxamine

1 day 4 hours ago
Brain aging is a major factor in cognitive decline and Alzheimer's disease (AD) progression. Aging-induced microglial senescence critically drives inflammaging and brain aging processes. Nevertheless, the underlying reasons and mechanisms that promote microglial aging remain unclear. This study explores how 27-hydroxycholesterol (27-OHC), a key oxysterol, accelerates brain aging by promoting microglial senescence, iron overload, and neuroinflammation. Clinically, we observed a significant...
Chunyang Yu

Protective ApoE variants support neuronal function by effluxing oxidized phospholipids

1 day 4 hours ago
Apolipoprotein E (ApoE) mediates the bidirectional transport of lipids between cells. In the brain, this includes the transfer of lipids from neurons to glia. ApoE4, a major risk factor for Alzheimer's disease, impairs this transport pathway, increasing risk for neurodegeneration. ApoE2 and ApoE3 Christchurch (ApoE3Ch) confer resistance to disease, yet little is known regarding how these variants affect lipid trafficking. Here, we explored how lipoprotein particles containing different ApoE...
Isha Ralhan

The effect of shingles vaccination at different stages of the dementia disease course

1 day 4 hours ago
Using natural experiments, we have previously reported that live-attenuated herpes zoster (HZ) vaccination appears to have prevented or delayed dementia diagnoses in both Wales and Australia. Here, we find that HZ vaccination also reduces mild cognitive impairment diagnoses and, among patients living with dementia, deaths due to dementia. Exploratory analyses suggest that the effects are not driven by a specific dementia type. Our approach takes advantage of the fact that individuals who had...
Min Xie

Characteristics and mechanisms of cognitive impairment in Parkinson disease

1 day 4 hours ago
Cognitive impairment in people with Parkinson disease (PD) imposes a substantial societal burden: PD affects over 1% of the population aged 65 years and older, and 24-31% of individuals with this condition develop dementia and another 26% present with mild cognitive impairment. Given the increasing prevalence of PD in light of an ageing population, the challenge of PD-associated cognitive impairment is likely to intensify. In this Review, we highlight the latest research advances in...
Panteleimon Oikonomou

Peritumoral colonic epithelial cell-derived GDF15 sustains colorectal cancer via regulation of glycolysis and histone lactylation

1 day 4 hours ago
One of the most abundant cellular components of the normal adjacent tissue surrounding colorectal cancer is colonic epithelial cells (CECs); however, little is known about their interactions with tumor cells. Here we found that peritumoral CECs collaborate with cancer cells to orchestrate a pro-carcinogenic niche. In clinical cohort analyses, we show that growth differentiation factor 15 (GDF15) levels increase in normal adjacent tissue, in particular in CECs, at advanced disease and are...
Bingjie Guan

27-Hydroxycholesterol triggers microglial senescence subsequent to iron over-loading contributes to brain aging, suppressed by Deferoxamine

1 day 4 hours ago
Brain aging is a major factor in cognitive decline and Alzheimer's disease (AD) progression. Aging-induced microglial senescence critically drives inflammaging and brain aging processes. Nevertheless, the underlying reasons and mechanisms that promote microglial aging remain unclear. This study explores how 27-hydroxycholesterol (27-OHC), a key oxysterol, accelerates brain aging by promoting microglial senescence, iron overload, and neuroinflammation. Clinically, we observed a significant...
Chunyang Yu

Time-restricted feeding rescues sociability deficits and reduces neuroinflammation in aged mice

1 day 4 hours ago
The aging brain exhibits an increased inflammatory potential which in turn elicits behavioral changes e.g., social withdrawal. Social isolation is a risk factor for additional health complications, and interventions which can mitigate these negative facets of aging can improve longevity and quality of life in old age. The circadian system critically regulates neuroimmune function and behavior, but circadian rhythms also degrade with age, resulting in lower amplitude oscillations in activity and...
Louise M Ince

High Torque teno virus viremia predicts long-term mortality and reflects chronic low-grade inflammation (inflammaging) in geriatric inpatients

1 day 4 hours ago
Torque teno virus (TTV) is a ubiquitous virus whose viremia increases in conditions of immune dysfunction and aging, suggesting its potential role as a biomarker of immunosenescence. This study investigated the association between TTV viremia and all-cause mortality risk over seven years in a hospitalized older cohort, and its relationship with inflammatory markers including osteopontin (OPN) and growth differentiation factor 15 (GDF15). Data from 956 patients were analyzed, with high TTV load...
Laura Cianfruglia

Vacuolar-type H<sup>+</sup>-ATPase-mediated extra-organellar buffering resolves mitochondrial dysfunction

1 day 4 hours ago
Mitochondrial dysfunction underlies a wide range of human diseases, including primary mitochondrial disorders, neurodegeneration, cancer, and ageing. To preserve cellular homeostasis, organisms have evolved adaptive mechanisms that coordinate nuclear and mitochondrial gene expression. Here, we use genome-wide CRISPR knockout screening to identify cell fitness pathways that support survival under impaired mitochondrial protein synthesis. The strongest suppressor of aberrant mitochondrial...
Geoffray Monteuuis

Longitudinal proteomic profiling of cerebrospinal fluid in untreated multiple sclerosis defines evolving disease biology

1 day 4 hours ago
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, but the molecular mechanisms underlying its course remain incompletely understood. We measured 4789 cerebrospinal fluid proteins in 1040 samples from 438 individuals with MS and controls followed longitudinally. To isolate disease-related biology, we adjusted for normal aging, sex, while also measuring residual effects of demographic and genetic covariates. Here we show that 3714 proteins are significantly...
Peter Kosa

Characteristics and mechanisms of cognitive impairment in Parkinson disease

1 day 4 hours ago
Cognitive impairment in people with Parkinson disease (PD) imposes a substantial societal burden: PD affects over 1% of the population aged 65 years and older, and 24-31% of individuals with this condition develop dementia and another 26% present with mild cognitive impairment. Given the increasing prevalence of PD in light of an ageing population, the challenge of PD-associated cognitive impairment is likely to intensify. In this Review, we highlight the latest research advances in...
Panteleimon Oikonomou

Advancing integration in the approach to older adults with HIV: perspectives from geriatric and HIV specialists

1 day 4 hours ago
CONCLUSIONS: This study highlights significant gaps in knowledge, training, and interdisciplinary collaboration in the care of OAWH. While both geriatricians and HIV specialists recognize the unique needs of this population, barriers such as insufficient training and role ambiguity hinder progress. Our findings support earlier, biologically informed interventions and integration of geriatrics into routine HIV care; targeted training and institutional support appear warranted.
Carmen M Cano

Age-related decline of chaperone-mediated autophagy in skeletal muscle leads to progressive myopathy

1 day 4 hours ago
Chaperone-mediated autophagy (CMA) contributes to proteostasis maintenance by selectively degrading a subset of proteins in lysosomes. CMA declines with age in most tissues, including skeletal muscle. However, the role of CMA in skeletal muscle and the consequences of its decline remain poorly understood. Here we demonstrate that CMA regulates skeletal muscle function. We show that CMA is upregulated in skeletal muscle in response to starvation, exercise and tissue repair, but declines in ageing...
Olaya Santiago-Fernández