An Overview of Neuromuscular Junction Aging Findings in Human and Animal Studies

Abstract

Background: Aging is a complex irreversible process that is not only related to an individual’s genetic make-up but also to lifestyle choices and environmental exposures. Like every other structure in human body, the Neuromuscular Junction (NMJ) is not averse to aging. Objectives: The prime objective is to analyse the microscopic and macroscopic changes at the NMJs with aging. Methods: For the purpose of review we evaluated data from resources like Pubmed, Ovid, UCLA libraries and USC libraries. Results: We review various morphological, physiological, immunological, and biochemical changes in NMJs with aging and their management. Conclusion: The alterations in NMJs secondary to aging are inevitable. It is vital that neurologists clearly understand the pathophysiology of NMJ aging and differentiate between physiological and pathological effects of aging. With the current knowledge of science, the changes in NMJ aging can be better prevented rather than cured.

Adaptive Remodeling of the Neuromuscular Junction with Aging

“…For example, aging has been found to bring about enhanced presynaptic nerve terminal branching, both as revealed by an increase in the total length of nerve terminal branches [ 43 , 44 , 45 ], and the number of terminal branches present at the NMJ [ 44 , 45 , 46 ]. Moreover, the complexity of this branching—with essentially, the total branch length as a factor of the branch number (please see figure legend for details)—has been found to be greater among aged nerve terminals than young ones [ 47 , 48 , 49 , 50 ]. It has been suggested that this indicates greater remodeling of the motor neuron in an attempt to improve communication between pre- and postsynaptic components of the NMJ, as such communication is pared down with aging [ 9 , 51 ].…”

Motoneuron deafferentation and gliosis occur in association with neuromuscular regressive changes during ageing in mice

“…Some studies have provided information indicating that an impaired neuromuscular innervation could account for the loss of muscle mass in advanced ages 9 ; in line with this, structural changes in both the presynaptic and postsynaptic portions of the neuromuscular junction (NMJ) have been reported to occur with age in both animals and humans. [10][11][12] Other studies in aged rodents have reported morphological alterations in motor nerve terminals with increased extent and complexity of their arborization, accompanied by fragmentation of postsynaptic endplates. All these changes appear to reflect continuous cycles of muscle denervation and reinnervation with ageing.…”

The TOR Pathway at the Neuromuscular Junction: More Than a Metabolic Player?

“…Several, sometimes contradictory, reports point to changes in the motor neuron terminal organization and in neurotransmission ( Gutmann et al, 1971 ; Banker et al, 1983 ; Smith, 1984 ; Chen et al, 2012 ; Mahoney et al, 2014 ). These pre-synaptic changes may actually well be the attempts to compensate for post-synaptic decline ( Courtney and Steinbach, 1981 ; Arizono et al, 1984 ; Khosa et al, 2019 ), and may arise from retrograde feedback from muscle onto the motor neuron ( Ouanounou et al, 2016 ). Hence, destabilization of the post-synaptic compartment is likely a primary event in the progressive loss of integrity of NMJs and muscle, and may in particular lead to the degeneration of the motor neuron in a dying back process ( Chai et al, 2011 ; Chung et al, 2017 ; Sheth et al, 2018 ).…”