Coenzyme Q10, Ageing and the Nervous System: An Overview

The ageing brain is characterised by changes at the physical, histological, biochemical and physiological levels. This ageing process is associated with an increased risk of developing a number of neurological disorders, notably Alzheimer’s disease and Parkinson’s disease. There is evidence that mitochondrial dysfunction and oxidative stress play a key role in the pathogenesis of such disorders. In this article, we review the potential therapeutic role in these age-related neurological disorders of supplementary coenzyme Q10, a vitamin-like substance of vital importance for normal mitochondrial function and as an antioxidant. This review is concerned primarily with studies in humans rather than in vitro studies or studies in animal models of neurological disease. In particular, the reasons why the outcomes of clinical trials supplementing coenzyme Q10 in these neurological disorders is discussed.

Deep neural networks learn general and clinically relevant representations of the ageing brain

The discrepancy between chronological age and the apparent age of the brain based on neuroimaging data - the brain age delta - has emerged as a reliable marker of brain health. With an increasing wealth of data, approaches to tackle heterogeneity in data acquisition are vital. To this end, we compiled raw structural magnetic resonance images into one of the largest and most diverse datasets assembled (n=53542), and trained convolutional neural networks (CNNs) to predict age. We achieved state-of-the-art performance on unseen data from unknown scanners (n=2553), and showed that higher brain age delta is associated with diabetes, alcohol intake and smoking. Using transfer learning, the intermediate representations learned by our model complemented and partly outperformed brain age delta in predicting common brain disorders. Our work shows we can achieve generalizable and biologically plausible brain age predictions using CNNs trained on heterogeneous datasets, and transfer them to clinical use cases.

The Ageing Brain: Molecular and Cellular Basis of Neurodegeneration

Ageing is an inevitable event in the lifecycle of all organisms, characterized by progressive physiological deterioration and increased vulnerability to death. Ageing has also been described as the primary risk factor of most neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and frontotemporal lobar dementia (FTD). These neurodegenerative diseases occur more prevalently in the aged populations. Few effective treatments have been identified to treat these epidemic neurological crises. Neurodegenerative diseases are associated with enormous socioeconomic and personal costs. Here, the pathogenesis of AD, PD, and other neurodegenerative diseases has been presented, including a summary of their known associations with the biological hallmarks of ageing: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, mitochondrial dysfunction, cellular senescence, deregulated nutrient sensing, stem cell exhaustion, and altered intercellular communications. Understanding the central biological mechanisms that underlie ageing is important for identifying novel therapeutic targets for neurodegenerative diseases. Potential therapeutic strategies, including the use of NAD+ precursors, mitophagy inducers, and inhibitors of cellular senescence, has also been discussed.

Ageing and Olfactory Dysfunction in Trisomy 21: A Systematic Review

Purpose: The olfactory system is particularly vulnerable in an ageing brain, both anatomically and functionally, and these brain changes are more pronounced among individuals with trisomy 21. Furthermore, the age of the system starts to deteriorate, and the mechanism involved is unclear in an individual with trisomy 21. Therefore, the present review aims to summarise the available information related to this topic and to suggest questions still unanswered which can be a subject of further research. Methods: A systematic literature search of trisomy 21 and olfactory dysfunction was conducted using PubMed/MEDLINE and Scopus electronic database following PRISMA guidelines. References and citations were checked in the Google Scholar database. Reports were extracted for information on demographics and psychophysical evaluation. Then, the reports were systematically reviewed based on the effects of ageing on the three olfactory domains: threshold, discrimination, and identification. Results: Participants with trisomy 21 show an early onset of olfactory impairment, and the age effect of the olfactory deficit is fully expressed at age > 30 years old. The three olfactory domains, threshold, discrimination, and identification, are suggested to be impaired in trisomy 21 participants with age > 30 years old. Conclusions: Olfactory dysfunction in an individual with trisomy 21 commences at a relatively young age and affects the three olfactory domains. A challenge for the future is to quantitatively establish the olfactory function of an individual with trisomy 21 at all ages with more detailed measurements to further understand the pathophysiology of this brain deterioration.