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Coenzyme Q headgroup intermediates can ameliorate a mitochondrial encephalopathy

1 year 3 months 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

1 year 3 months 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

1 year 3 months 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

1 year 3 months 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

1 year 3 months 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

Transcriptional Diversity in Response to Aging Across Skeletal Muscles

1 year 3 months ago
Aging leads to a gradual decline in muscle function, yet the mechanisms by which different skeletal muscles respond to aging remain unclear. Here, we constructed transcriptional maps of 11 skeletal muscles with extensive transcriptional diversity from young and old mice. Age-related changes in gene expression displayed distinct tissue-specific patterns, involving muscle diseases and metabolic processes. Notably, the mitochondrial-enriched soleus muscle exhibited superior resistance to aging...
Can Liu

The hidden economic burden of cancer caring

1 year 3 months ago
CONCLUSION: The time spent caring for people living with cancer by informal carers is significant. Recognizing and rigorously investigating the role of informal cancer carers in reducing the burden on the formal care sector and improving the quality of life of people living with cancer is essential to understanding the impact and significance of caring, which will facilitate impactful policy changes.
Lan Gao

Neuroimmunology in ageing and longevity: a special collection issue of Biogerontology

1 year 3 months ago
Ageing is associated with neuroimmune shifts from a resting to a hyperactive and inflammatory state, termed 'Neuroinflammageing', attributed to microglial priming, hyperactive astrocytes, cytokine and chemokine release, blood brain barrier leakage, and infiltration of peripheral immune cells. This special issue of Biogerontology on 'Neuroimmunology in Ageing and Longevity' brings together 11 reviews and original research papers dealing with the complex cross-talk between CNS and peripheral...
Gurcharan Kaur