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APOE3 Christchurch Heterozygosity and Autosomal Dominant Alzheimer's Disease
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APOE3 Christchurch Heterozygosity and Autosomal Dominant Alzheimer's Disease. Reply
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Maternal genetic variants in kinesin motor domains prematurely increase egg aneuploidy
The female reproductive lifespan is highly dependent on egg quality, especially the presence of a normal number of chromosomes in an egg, known as euploidy. Mistakes in meiosis leading to egg aneuploidy are frequent in humans. Yet, knowledge of the precise genetic landscape that causes egg aneuploidy in women is limited, as phenotypic data on the frequency of human egg aneuploidy are difficult to obtain and therefore absent in public genetic datasets. Here, we identify genetic determinants of...
Elucidating ATP's role as solubilizer of biomolecular aggregate
Proteins occurring in significantly high concentrations in cellular environments (over 100 mg/ml) and functioning in crowded cytoplasm, often face the prodigious challenges of aggregation which are the pathological hallmark of aging and are critically responsible for a wide spectrum of rising human diseases. Here, we combine a joint-venture of complementary wet-lab experiment and molecular simulation to discern the potential ability of adenosine triphosphate (ATP) as solubilizer of protein...
Microglia cannibalism and efferocytosis leads to shorter lifespans of developmental microglia
The overproduction of cells and subsequent production of debris is a universal principle of neurodevelopment. Here, we show an additional feature of the developing nervous system that causes neural debris-promoted by the sacrificial nature of embryonic microglia that irreversibly become phagocytic after clearing other neural debris. Described as long-lived, microglia colonize the embryonic brain and persist into adulthood. Using transgenic zebrafish to investigate the microglia debris during...
Aging disrupts blood-brain and blood-spinal cord barrier homeostasis, but does not increase paracellular permeability
Blood-CNS barriers protect the CNS from circulating immune cells and damaging molecules. It is thought barrier integrity becomes disrupted with aging, contributing to impaired CNS function. Using genome-wide and targeted molecular approaches, we found aging affected expression of predominantly immune invasion and pericyte-related genes in CNS regions investigated, especially after middle age, with spinal cord being most impacted. We did not find significant perturbation of endothelial cell...
White matter integrity and motor function: a link between cerebral myelination and longitudinal changes in gait speed in aging
Gait speed is a robust health biomarker in older adults, correlating with the risk of physical and cognitive impairments, including dementia. Myelination plays a crucial role in neurotransmission and consequently affects various functions, yet the connection between myelination and motor functions such as gait speed is not well understood. Understanding this link could offer insights into diagnosing and treating neurodegenerative diseases that impair mobility. This study analyzed 437...
Age-related increase in the excitability of mouse layer V pyramidal neurons in the primary motor cortex is accompanied by an increased persistent inward current
Sarcopenia, or pathological age-related loss of muscle strength and mass, contributes to physical function impairment in older adults. While current understanding of sarcopenia is centered mostly on neuromuscular mechanisms, mounting evidence supports that deficits at the level of the primary motor cortex (PMC) play a significant role. Despite the importance of the PMC to initiate movement, understanding of how age affects the excitability of layer V pyramidal neurons (LVPNs) of the PMC is...
Systems biology approaches identify metabolic signatures of dietary lifespan and healthspan across species
Dietary restriction (DR) is a potent method to enhance lifespan and healthspan, but individual responses are influenced by genetic variations. Understanding how metabolism-related genetic differences impact longevity and healthspan are unclear. To investigate this, we used metabolites as markers to reveal how different genotypes respond to diet to influence longevity and healthspan traits. We analyzed data from Drosophila Genetic Reference Panel (DGRP) strains raised under AL and DR conditions,...
Author Correction: Transiently formed nucleus-to-cilium microtubule arrays mediate senescence initiation in a KIFC3-dependent manner
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Causal inference for epigenetic ageing
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"The stay here is, of course, not appropriate for an old person": the perspective of healthcare providers on older patients in the emergency department
CONCLUSION: Healthcare providers experience a structural mismatch between contemporary EDs and the specific needs of geriatric patients. They are aware of the vulnerabilities of geriatric patients and try to compensate for inherent structural shortcomings. Such structures and limited resources often cause practical, organizational, and ethical problems. There is a great need to develop, implement, and evaluate systematic approaches and care concepts that address the specifics of ED care for...
Machine learning-based personalized composite score dissects risk and protective factors for cognitive and motor function in older participants
INTRODUCTION: With age, sensory, cognitive, and motor abilities decline, and the risk for neurodegenerative disorders increases. These impairments influence the quality of life and increase the need for care, thus putting a high burden on society, the economy, and the healthcare system. Therefore, it is important to identify factors that influence healthy aging, particularly ones that are potentially modifiable through lifestyle choices. However, large-scale studies investigating the influence...