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Disrupted lipid homeostasis and neuroinflammation often co-exist in neurodegenerative disorders, including Alzheimer's disease (AD). However, the intrinsic connection and causal relationship between these deficits remain elusive. Our previous studies show that the loss of sulfatide (ST), a class of myelin-enriched lipids, causes AD-like neuroinflammatory responses, cognitive impairment, bladder enlargement, and lipid dyshomeostasis. To better understand the relationship between neuroinflammation...

Alzheimer's disease (AD) is a devastating neurodegenerative disease and the most prevalent type of dementia characterized by pathological deposition of amyloid-β plaques/deposits and tau tangles within the brain parenchyma. This progressive ailment is featured by irreversible cognitive impairment and memory loss, often misdiagnosed as the consequence of old age in elderlies. Pathologically, synaptic dysfunction occurs at the early stages and then progresses into neurodegeneration with neuronal...

Deposition of amyloid proteins and their associated interactome is a hallmark of Alzheimer's disease (AD) and other amyloidosis diseases, with their composition implying disease etiology. However, precise in-situ micro-dissection of amyloid deposits in AD brain tissue remains a challenge. In this work, we first divert the excited state energy of Thioflavin T from singlet fluorescence to triplet photocatalytic amyloid protein labeling through molecular engineering, while maintain its pan-amyloid...

Freezing of gait (FOG) is among the most debilitating symptoms of Parkinson disease and related disorders, often resulting in falls and a loss of independence. FOG has an episodic and heterogeneous nature that makes it difficult to measure and treat. The field currently lacks a consensus on how to precisely define this phenomenon. For this reason, the International Consortium for Freezing of Gait convened a group of experts to establish an updated 'clinical' definition of FOG for use in the...

Aging is characterized by a progressive decline in physiological function, driven by interconnected molecular hallmarks that increase the risk of chronic diseases. To extend health span, interventions targeting these hallmarks, including lifestyle modifications, pharmacological agents, and genetic strategies, have been developed. Among these, partial reprogramming, the transient expression of Yamanaka factors, has emerged as a powerful approach to reverse age-related cellular damage and restore...

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID are two post-viral diseases, which share many common symptoms and pathophysiological alterations. Yet a mechanistic explanation of disease induction and maintenance is lacking. This hinders the discovery and implementation of biomarkers and treatment options, and ultimately the establishment of effective clinical resolution. Here, we propose that acute viral infection results in (in)direct endothelial dysfunction and...

Retroviruses that colonize the host germline can be passed on as inherited genetic variants. The koala (Phascolarctos cinereus) is currently experiencing germline colonization by two retroviruses, the koala retrovirus (KoRV) and phaCin-β. We analyze the integration site segregation and diversity of endogenous KoRV, phaCin-β, and the related phaCin-β-like in 111 pedigreed koalas from the San Diego Zoo Wildlife Alliance and seven European Zoos. The use of multigenerational pedigrees and the...

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Multiple myeloma (MM) remains incurable despite advances in treatment options. Although tumor subtypes and specific DNA abnormalities are linked to worse prognosis, the impact of immune dysfunction on disease emergence and/or treatment sensitivity remains unclear. We developed an Immune Atlas of MM by generating profiles of 1,397,272 single cells from the bone marrow (BM) of 337 newly diagnosed participants and characterized immune and hematopoietic cell populations. Cytogenetic risk-based...

Social housing is desirable for the health and well-being of laboratory mice, as social interactions with conspecifics influence both behavioral and physiological outcomes. Although group housing benefits social species, it can introduce variability in mortality outcomes, and raise welfare concerns, particularly with the emergence of aggression or fluctuating cage densities. Despite this, few studies have evaluated how changes in the number of living cagemates over time are associated with...

Biological regulation is an intricate process involving many layers of complexity, including at the RNA level. Alternative splicing is crucial in the regulation of which components of a protein-coding gene are spliced into a translatable mRNA. During ageing, splicing becomes dysregulated, and alternative splicing is implicated in disease and known anti-ageing treatments such as dietary restriction (DR) and mTOR suppression. In prior work, we have shown that DR and mTOR suppression modulate the...

Ferroptosis, an iron-dependent form of regulated cell death, is increasingly recognized as a key contributor to aging-associated skeletal muscle degeneration and dysfunction. However, the interactive effects of aging, sex, and exercise modality on ferroptosis regulatory markers at the histological, protein, and gene expression levels remain poorly understood. Male (n = 23) and female (n = 23) mice aged 7 (young) and 17 (aged) months were assigned to sedentary control, voluntary wheel running, or...

CONCLUSION: RT is an effective intervention for improving cognition, memory, depression, and quality of life in older adults with cognitive impairment or dementia. Patient age, intervention frequency, and setting are potential moderators of its cognitive efficacy, providing actionable insights for optimizing clinical RT protocols.

CONCLUSION: Coal use increases the risk of cognitive decline, whereas higher social engagement is protective; these influences operate independently without evidence of interaction. Reducing household reliance on coal while promoting meaningful social participation may represent complementary strategies to preserve cognitive health in aging populations.

Epigenetic mechanisms, including histone acetylation, regulate learning and memory and underlie Alzheimer's disease and related dementia (ADRD). Acetyl-CoA synthetase 2 (ACSS2), an enzyme generating acetyl-CoA, locally regulates histone acetylation and gene expression in neuronal nuclei. This regulatory mechanism may be a promising target for therapeutic intervention in neurodegenerative diseases. Previously, we showed that systemic ACSS2 knockout mice, although largely normal in physiology,...

Protein misfolding in the brain is a key pathological hallmark of neurodegenerative diseases. Optical imaging of misfolded proteins in disease models is essential for elucidating etiology and early diagnosis. However, developing specific optical imaging probes for each misfolded protein is time-consuming and challenging, leaving many pathological targets without effective detection tools, especially for in vivo imaging. Here, we present a dual-mode chemiluminescence strategy that enables both...

Many biological functions and dysfunctions rely on two fundamental processes, molecular assembly and the formation of condensed phases such as biomolecular condensates. Condensed phases generally form via phase separation, while molecular assemblies are clusters of molecules of various sizes, shapes, and functionality. We developed a theory that relies on thermodynamic principles to understand the interplay between molecular assembly and phase separation. We propose two prototypical classes of...

CONCLUSION: With very low to moderate certainty, probiotics, prebiotics, and synbiotics may improve constipation and motor symptoms in PD compared to placebo. These findings suggest a potential benefit, but more high-quality research is needed to confirm these effects and establish stronger evidence.

Epigenetic mechanisms, including histone acetylation, regulate learning and memory and underlie Alzheimer's disease and related dementia (ADRD). Acetyl-CoA synthetase 2 (ACSS2), an enzyme generating acetyl-CoA, locally regulates histone acetylation and gene expression in neuronal nuclei. This regulatory mechanism may be a promising target for therapeutic intervention in neurodegenerative diseases. Previously, we showed that systemic ACSS2 knockout mice, although largely normal in physiology,...

Cellular rejuvenation through transcriptional reprogramming is an exciting approach to counter aging. Using a fibroblast-based model of human cell aging and Perturb-seq screening, we developed a systematic approach to identify single transcription factor (TF) perturbations that promote rejuvenation without dedifferentiation. Overexpressing E2F3 or EZH2, and repressing STAT3 or ZFX, reversed cellular hallmarks of aging-increasing proliferation, proteostasis, and mitochondrial activity, while...