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Hippocampal neural stem cell exosomes promote brain resilience against the impact of tau oligomers

3 months 3 weeks ago
A promising therapeutic intervention for preventing the onset and progression of Alzheimer's Disease (AD) is to protect and improve synaptic resilience, a well-established early vulnerability associated with the toxic effects of oligomers of Aβ (AβO) and Tau (TauO). We have previously reported that exosomes from hippocampal neural stem cells (NSCs) protect synapses against AβO. Here, we demonstrate how exosomes can also shield against TauO toxicity in adult mice synapses, potentially benefiting...
Balaji Krishnan

Microglial mechanisms drive amyloid-beta clearance in immunized patients with Alzheimer's disease

3 months 3 weeks ago
Alzheimer's disease (AD) therapies utilizing amyloid-β (Aβ) immunization have shown potential in clinical trials. Yet, the mechanisms driving Aβ clearance in the immunized AD brain remain unclear. Here, we use spatial transcriptomics to explore the effects of both active and passive Aβ immunization in the AD brain. We compare actively immunized patients with AD with nonimmunized patients with AD and neurologically healthy controls, identifying distinct microglial states associated with Aβ...
Lynn van Olst

Mitochondria-enriched hematopoietic stem cells exhibit elevated self-renewal capabilities, thriving within the context of aged bone marrow

3 months 3 weeks ago
The aging of hematopoietic stem cells (HSCs) substantially alters their characteristics. Mitochondria, essential for cellular metabolism, play a crucial role, and their dysfunction is a hallmark of aging-induced changes. The impact of mitochondrial mass on aged HSCs remains incompletely understood. Here we demonstrate that HSCs with high mitochondrial mass during aging are not merely cells that have accumulated damaged mitochondria and become exhausted. In addition, these HSCs retain a high...
Haruhito Totani

Various diseases and conditions are strongly associated with the next-generation epigenetic aging clock CheekAge

3 months 3 weeks ago
Epigenetic aging clocks represent contemporary aging biomarkers that predict age using methylomic data. These models can be categorized as first-generation clocks that estimate chronological age or next-generation clocks that are designed to associate with health, lifestyle, and/or outcomes. Recently, we created a next-generation buccal clock called CheekAge that associates with all-cause mortality risk in older adults. To better understand our model, we collated 25 Infinium MethylationEPIC...
Maxim N Shokhirev

Construction and validation of a DNN-based biological age and its influencing factors in the China Kadoorie Biobank

3 months 3 weeks ago
Biological age is an important measure of aging that reflects an individual's physical health and is linked to various diseases. Current prediction models are still limited in precision, and the risk factors for accelerated aging remain underexplored. Therefore, we aimed to develop a precise biological age and assess the impact of socio-demographic and behavioral patterns on the aging process.We utilized Deep Neural Networks (DNN) to construct biological age from participants with physical...
Yushu Huang

Cryptic mitochondrial DNA mutations coincide with mid-late life and are pathophysiologically informative in single cells across tissues and species

3 months 3 weeks ago
Ageing is associated with a range of chronic diseases and has diverse hallmarks. Mitochondrial dysfunction is implicated in ageing, and mouse-models with artificially enhanced mitochondrial DNA mutation rates show accelerated ageing. A scarcely studied aspect of ageing, because it is invisible in aggregate analyses, is the accumulation of somatic mitochondrial DNA mutations which are unique to single cells (cryptic mutations). We find evidence of cryptic mitochondrial DNA mutations from diverse...
Alistair P Green