Lipid (per) oxidation in mitochondria:an emerging target in the ageing process?

Lipids are essential for physiological processes such as maintaining membrane integrity, providing a source of energy and acting as signalling molecules to control processes including cell proliferation, metabolism, inflammation and apoptosis. Disruption of lipid homeostasis can promote pathological changes that contribute towards biological ageing and age-related diseases. Several age-related diseases have been associated with altered lipid metabolism and an elevation in highly damaging lipid peroxidation products; the latter has been ascribed, at least in part, to mitochondrial dysfunction and elevated ROS formation. In addition, senescent cells, which are known to contribute significantly to age-related pathologies, are also associated with impaired mitochondrial function and changes in lipid metabolism. Therapeutic targeting of dysfunctional mitochondrial and pathological lipid metabolism is an emerging strategy for alleviating their negative impact during ageing and the progression to age-related diseases. Such therapies could include the use of drugs that prevent mitochondrial uncoupling, inhibit inflammatory lipid synthesis, modulate lipid transport or storage, reduce mitochondrial oxidative stress and eliminate senescent cells from tissues. In this review, we provide an overview of lipid structure and function, with emphasis on mitochondrial lipids and their potential for therapeutic targeting during ageing and age-related disease

Cholinergic receptor pathways involved in apoptosis, cell proliferation and neuronal differentiation

Acetylcholine (ACh) has been shown to modulate neuronal differentiation during early development. Both muscarinic and nicotinic acetylcholine receptors (AChRs) regulate a wide variety of physiological responses, including apoptosis, cellular proliferation and neuronal differentiation. However, the intracellular mechanisms underlying these effects of AChR signaling are not fully understood. It is known that activation of AChRs increase cellular proliferation and neurogenesis and that regulation of intracellular calcium through AChRs may underlie the many functions of ACh. Intriguingly, activation of diverse signaling molecules such as Ras-mitogen-activated protein kinase, phosphatidylinositol 3-kinase-Akt, protein kinase C and c-Src is modulated by AChRs. Here we discuss the roles of ACh in neuronal differentiation, cell proliferation and apoptosis. We also discuss the pathways involved in these processes, as well as the effects of novel endogenous AChRs agonists and strategies to enhance neuronal-differentiation of stem and neural progenitor cells. Further understanding of the intracellular mechanisms underlying AChR signaling may provide insights for novel therapeutic strategies, as abnormal AChR activity is present in many diseases

Physiological indicators of driver workload during car-following scenarios and takeovers in highly automated driving

This driving simulator study, conducted as a part of Horizon2020-funded L3Pilot project, investigated how different car-following situations affected driver workload, within the context of vehicle automation. Electrocardiogram (ECG) and electrodermal activity (EDA)-based physiological metrics were used as objective indicators of workload, along with self-reported workload ratings. A total of 32 drivers were divided into two equal groups, based on whether they engaged in a non-driving related task (NDRT) during automation (SAE Level 3) or monitored the drive (SAE Level 2). Drivers in both groups were exposed to two counterbalanced experimental drives, lasting ∼ 18 min each, of Short (0.5 s) and Long (1.5 s) Time Headway conditions during automated car-following (ACF), which was followed by a takeover that happened with or without a lead vehicle. Results showed that driver workload due to the NDRT was significantly higher than both monitoring the drive during ACF and manual car-following (MCF). Furthermore, the results indicated that a lead vehicle maintain a shorter THW can significantly increase driver workload during takeover scenarios, potentially affecting driver safety. This warrants further research into understanding safe time headway thresholds to be maintained by automated vehicles, without placing additional cognitive or attentional demands on the driver. Our results indicated that ECG and EDA signals are sensitive to variations in workload, which warrants further investigation on the value of combining these two signals to assess driver workload in real-time, to help future driver monitoring systems respond appropriately to the limitations of the driver, and predict their performance in the driving task, if and when they have to resume manual control of the vehicle after a period of automated driving

Transport Policy Measures for Climate Change as Drivers for Health in Cities

Climate change is an urgent challenge that requires action at the national, regional and local levels. However, a perception that impacts on human wellbeing and the economy will only be felt in the distant future, and a belief that climate action would require reducing attention towards a host of other environmental and societal issues, stand in the way of measures being taken. With cities emerging as key actors in fighting climate change as well as other societal and environmental issues, this chapter provides a review of the ways urban climate action provides direct and more immediate benefits —in climate terms, ‘co-benefits’— to public health. We focus on the impacts of five key transport policy measures which have been established to yield significant greenhouse gas reductions and substantial economic benefits. These are: (1) compact land use planning to reduce motorised passenger travel demand, (2) passenger modal shift and improving transit efficiency, (3) electrification and passenger vehicle efficiency, (4) freight logistics and (5) freight vehicle efficiency and electrification. We show that these measures have great potential to improve public health in urban areas whilst mitigating climate change, and provide arguments that in some cases these benefits may rival, or exceed, benefits to the economy and climate from these actions. We conclude that climate change action in the transport sector represents a great opportunity for policymakers to develop transport roadmaps that jointly achieve climate change objectives and improve public health in cities