Editorial

There are a wealth of articles on ageing and neurodegeneration and clear links with diseases such as Parkinson's and Alzheimer's, but what of the broader physiological context in which cognitive decline and movement disorders are associated with normal ageing? Many of the articles in this issue arose from a meeting on ‘Ageing and Degeneration: A Physiological Perspective’ which was hosted by The Physiological Society and held in Edinburgh on 10–11 April 2015. The programme brought together a diverse range of talents, opening with a plenary lecture on ‘Healthy cognitive ageing’ given by Ian Deary (University of Edinburgh). His work in analysing many aspects of cognition and genetics across the lifespan, through examination of the Lothian Birth cohort, has provided many new insights into ageing (see Marioni et al. 2015). The symposia built through sessions on the role of exercise and cardiovascular fitness in cognition (organized by Marc Poulin, Canada), the pathophysiology of balance and increased risks of falling (Simon Gandevia, Australia) to the limitations of muscle blood flow and micro-vascular function in ageing (Ylva Hellsten, Denmark). Links between physical activity and neurodegeneration (Paul Greenhaff, UK) provided insights into age-related changes in the human and, at the cellular level, ageing-associated changes in lipid raft membrane biology and function (Brian Head, USA). The meeting concluded with a session covering the spectrum of molecular mechanisms of cerebellar ataxias that underlie these movement disorders and provided insights into potential mechanisms of degeneration (Mandy Jackson and Ian Forsythe, UK). In this issue we have a series of Topical Reviews, Symposium Reviews and Research papers highlighting aspects of the physiology of ageing in excitable cells. The first series of reviews links the cardiovascular system, exercise and diet in maintaining brain function by considering cerebral perfusion during exercise in the aged (Braz & Fisher, 2016) and how human trials of different lifestyle behaviours suggest means to combat cognitive impairment (Jackson et al. 2016). A mitochondrial perspective on the cellular mechanisms underlying neuromuscular transmission and function provides an overview of sarcopenia and potential countermeasures to this decline during ageing (Rygiel et al. 2016). Physiological measurement and profiling of the decline of performance, motor impairment and other physiological systems in humans are suggesting interventions which can maintain health across the lifespan (Lord et al. 2016). These age-related neuromuscular changes are characterized by loss of motoneurons, enlargement of motor units and associated loss in synaptic function and muscle mass, which have been carefully studied using electromyography in the vastus lateralis (Piasecki et al. 2016). These concepts of disruption in neuromuscular systems and locomotion are major contributors to the increased incidence of falls in the aged and this is reviewed in relation to the process and protection of stepping in reducing the risk of falls by Rogers & Mille (2016). Ageing is also associated with changes in sensory function, which is highlighted here in relation to mechanosensory and chemosensory function in the gut (Keating et al. 2016) that contribute to gastrointestinal dysfunction and morbidity. At the cellular level, changes in membrane lipid rafts also contribute to loss of neuronal function (Egawa et al. 2016) and non-canonical functions for caveolin are suggested as playing key roles in cellular senescence, mitochondria and energy production (Schilling & Patel, 2016). The dynamics of reactive oxygen species (ROS) associated with muscle metabolism and ageing are also highlighted by a review of electron paramagnetic resonance spectroscopy (Abdel-Rahman et al. 2016) illustrating how this technique can probe the environment of stable radicals. Animal models of dementia are increasingly being employed to address mechanistic questions about memory deficits, as exemplified by Witton et al. (2016). The final section concerns the molecular and synaptic mechanism of cerebellar ataxia and neurodegeneration. These disorders are diverse, heterogeneous and classified into a series of over 30 distinct genetic diseases – the spinocerebellar ataxias (SCA, see Jayadev & Bird, 2013 for an overview). In the first of our reviews Gary Stephens describes the evidence for an endocannabinoid pathway in the cerebellum that may have therapeutic utility (Stephens, 2016). This theme continues with a hypothesis for a role of metabotropic glutamate receptors (type 1) signalling in mouse models of cerebellar ataxia (Power et al. 2016) and disrupted calcium signalling forming an early pathophysiological mechanism (Meera et al. 2016). A common theme in these SCA diseases is structural and associated with ion channel location; for example SCA5 and related ataxias are associated with mutations of the cytoskeletal protein β-III spectrin (Perkins et al. 2016). Such induced changes in cerebellar excitability suggest insights into common molecular mechanisms of normal cognitive ageing. Associations of specific ion channels mediating regulation of neuron excitability (such as Kv3.3 potassium channels in cerebellar Purkinje neurons, SCA13; Zhang & Kaczmarek, 2016) point to excitotoxicity as a neurodegenerative mechanism and suggest strategies for the development of treatments. This short series of reviews and research papers provides a physiological perspective on ageing and degeneration, and will stimulate further research in this important area.

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