Abstract

Age-related axon loss is a major contributor to cognitive decline and physical frailty during normal ageing. We lose 45% of the white matter in our brain by age 80 and 40% of our skin innervation by 60. Similar processes can be modelled in mice, which lose around 30% of tibial nerve axons and axonal arbors of retinal ganglion cells by 24 months. Age-related axon loss also reduces the scope for compensatory responses to neurodegenerative disease. Thus, even though mechanisms of age-related axon loss and disease may differ, this aspect of normal ageing is likely to accelerate symptom onset and underlie the fact that ageing is the biggest single risk factor for Alzheimer’s disease, Parkinson’s disease, motor neuron disease and other disorders.