Decoding the relationship between ageing and amyotrophic lateral sclerosis: a cellular perspective

Author:

Pandya Virenkumar A12,Patani Rickie12

Affiliation:

1. Department of Neuromuscular Diseases, University College London Queen Square Institute of Neurology, Queen Square, London, UK

2. The Francis Crick Institute, London, UK

Abstract

Abstract With an ageing population comes an inevitable increase in the prevalence of age-associated neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), a relentlessly progressive and universally fatal disease characterized by the degeneration of upper and lower motor neurons within the brain and spinal cord. Indeed, the physiological process of ageing causes a variety of molecular and cellular phenotypes. With dysfunction at the neuromuscular junction implicated as a key pathological mechanism in ALS, and each lower motor unit cell type vulnerable to its own set of age-related phenotypes, the effects of ageing might in fact prove a prerequisite to ALS, rendering the cells susceptible to disease-specific mechanisms. Moreover, we discuss evidence for overlap between age and ALS-associated hallmarks, potentially implicating cell type-specific ageing as a key contributor to this multifactorial and complex disease. With a dearth of disease-modifying therapy currently available for ALS patients and a substantial failure in bench to bedside translation of other potential therapies, the unification of research in ageing and ALS requires high fidelity models to better recapitulate age-related human disease and will ultimately yield more reliable candidate therapeutics for patients, with the aim of enhancing healthspan and life expectancy.

Funder

Rosetrees Trust

University College London MBPhD Programme

MRC Senior Clinical Fellowship

Publisher

Oxford University Press (OUP)

Subject

Clinical Neurology

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