Selective vulnerability in adult and ageing mammalian neurons

Data are presented in support of the idea of antagonistic pleiotropy that features which are adaptive during early life may become maladaptive during the ageing process, when selective pressure is reduced. A model of selective vulnerability to age-related neurodegeneration involving neighbouring subpopulations of vulnerable and protected sympathetic neurons is presented. The two groups of neurons are morphologically and physiologically distinct, indicating advantageous adaptation to particular functions. Neurotrophin signalling is investigated in these different groups of neurons, revealing significant differences between them: neurotrophic factor expression in their target tissues is markedly different, same as their neurotrophin uptake characteristics. Preliminary evidence is presented that the mechanism linking neurotrophin signalling and age-related neurodegeneration may involve the capacity of neurons to buffer free radical generation, hence reducing the effects of attrition by free radical damage.