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Proposed “megaconstellations” would contaminate images from telescopes in low-Earth orbit, including Hubble

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...

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...

No abstract

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...

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...

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...

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...

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...

No abstract

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...

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...

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...

CONCLUSIONS: Elevated serum Cu/Zn ratio predicts adverse outcomes and sarcopenia, highlighting its value as a biomarker for clinical risk in older adults.

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...

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...

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...

No abstract

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.

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...