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How short peptides disassemble tau fibrils in Alzheimer's disease

3 months 3 weeks ago
Reducing fibrous aggregates of the protein tau is a possible strategy for halting the progression of Alzheimer's disease (AD)¹. Previously, we found that in vitro, the D-enantiomeric peptide (D-peptide) D-TLKIVWC disassembles ultra-stable tau fibrils extracted from the autopsied brains of individuals with AD (hereafter, these tau fibrils are referred to as AD-tau) into benign segments, with no energy source other than ambient thermal agitation². To consider D-peptide-mediated disassembly as a...
Ke Hou

Plasma proteomics links brain and immune system aging with healthspan and longevity

3 months 3 weeks ago
Plasma proteins derived from specific organs can estimate organ age and mortality, but their sensitivity to environmental factors and their robustness in forecasting onset of organ diseases and mortality remain unclear. To address this gap, we estimate the biological age of 11 organs using plasma proteomics data (2,916 proteins) from 44,498 individuals in the UK Biobank. Organ age estimates were sensitive to lifestyle factors and medications and were associated with future onset (within 17...
Hamilton Se-Hwee Oh

Early-life exercise extends healthspan but not lifespan in mice

3 months 3 weeks ago
It is well-known that physical activity exerts health benefits, yet the potential impacts of early-life regular exercise on later-life health and lifespan remains poorly understood. Here, we demonstrate that 3 months of early-life exercise in mice results in lasting health benefits, extending healthspan, but not lifespan. C57BL/6J mice underwent swimming exercise from 1 to 4 months of age, followed by detraining for the remainder of their lives. While early-life exercise did not extend the...
Mengya Feng

Aging-associated alterations in gene regulatory networks associate with risk, prognosis and response to therapy in lung adenocarcinoma

3 months 3 weeks ago
Aging is the primary risk factor for many cancer types, including lung adenocarcinoma (LUAD). To understand how aging-related alterations in the regulation of key cellular processes might affect LUAD risk and survival, we built individual-specific gene regulatory networks integrating gene expression, transcription factor protein-protein interaction, and sequence motif data, using PANDA/LIONESS algorithms, for non-cancerous lung samples from GTEx project and LUAD samples from TCGA. In healthy...
Enakshi Saha

Selective remodelling of the adipose niche in obesity and weight loss

3 months 3 weeks ago
Weight loss significantly improves metabolic and cardiovascular health in people with obesity^(1-3). The remodelling of adipose tissue (AT) is central to these varied and important clinical effects⁴. However, surprisingly little is known about the underlying mechanisms, presenting a barrier to treatment advances. Here we report a spatially resolved single-nucleus atlas (comprising 171,247 cells from 70 people) investigating the cell types, molecular events and regulatory factors that reshape...
Antonio M A Miranda

Coenzyme Q headgroup intermediates can ameliorate a mitochondrial encephalopathy

3 months 3 weeks ago
Decreased brain levels of coenzyme Q(10) (CoQ(10)), an endogenously synthesized lipophilic antioxidant^(1,2), underpin encephalopathy in primary CoQ(10) deficiencies^(3,4) and are associated with common neurodegenerative diseases and the ageing process^(5,6). CoQ(10) supplementation does not increase CoQ(10) pools in the brain or in other tissues. The recent discovery of the mammalian CoQ(10) headgroup synthesis pathway, in which 4-hydroxyphenylpyruvate dioxygenase-like protein (HPDL) makes...
Guangbin Shi

Plasma proteomics links brain and immune system aging with healthspan and longevity

3 months 3 weeks ago
Plasma proteins derived from specific organs can estimate organ age and mortality, but their sensitivity to environmental factors and their robustness in forecasting onset of organ diseases and mortality remain unclear. To address this gap, we estimate the biological age of 11 organs using plasma proteomics data (2,916 proteins) from 44,498 individuals in the UK Biobank. Organ age estimates were sensitive to lifestyle factors and medications and were associated with future onset (within 17...
Hamilton Se-Hwee Oh

Mitochondrial dysfunction and aging: multidimensional mechanisms and therapeutic strategies

3 months 3 weeks ago
Aging is an inherent phenomenon that is highly important in the pathological development of numerous diseases. Aging is a multidimensional phenomenon characterized by the progressive impairment of various cellular structures and organelle functions. The basis of human organ senescence is cellular senescence. Currently, with the increase in human life expectancy and the increasing proportion of the elderly population, the economic burden of diseases related to aging is becoming increasingly heavy...
Pei Wei

Synthetic efferocytic receptor microglia enhances anti-inflammatory clearance of amyloid-β for AD treatment in mice

3 months 3 weeks ago
Monoclonal antibody immunotherapy targeting the clearance of amyloid-β (Aβ) has shown promise in Alzheimer's disease (AD). However, current antibody treatments trigger Fc receptors and induce proinflammatory responses, in turn exacerbating neuronal damage. Here, we report a synthetic efferocytic receptor (SER) integrating Aβ-targeting scFv, efferocytosis receptor backbone based on TIM4 and downstream signal for microglia (MG) reprogramming, which enabled selective elimination of Aβ without...
Lijuan Shao

A mechanistic basis of fast myofiber vulnerability to neuromuscular diseases

3 months 3 weeks ago
Neuromuscular diseases such as amyotrophic lateral sclerosis and sarcopenia cause muscle atrophy, which preferentially affects fast-twitch glycolytic myofibers. The mechanisms underlying the susceptibility of fast myofibers to disease remain unclear. To investigate this, we analyzed the transcriptional profiles of myonuclei from denervated muscle fibers. We found that the fast muscle gene program and the transcription factor Maf were repressed upon denervation. Overexpression of Maf in mice...
Matthieu Dos Santos