Cell Maintenance and Stress Response in Ageing and Longevity

Abstract

Evolution theory suggests that ageing is caused by a life-long accumulation of random damage in somatic cells and tissues, due to an evolved limitation in the levels of key maintenance functions1. This idea, termed the disposable soma theory, predicts a central role for cell maintenance and stress response mechanisms in regulating the duration of life. There is potentially a large number of such mechanisms and individual theories have focused, in particular, on the roles of free radicals and oxidative damage, aberrant proteins, defective mitochondria, and somatic mutations. The disposable soma theory identifies a common ground for these ‘stochastic’ theories of ageing. Furthermore, since the same selection forces act to optimise the genetic control of diverse maintenance functions, the disposable soma theory predicts that multiple stochastic causes of ageing will operate together. Central to this concept is the fact that maintenance systems inevitably involve some costs. To the extent that these costs reduce the resources available for growth and reproduction, they will have a negative effect on Darwinian fitness. Thus, it is predicted that selection will ensure sufficient levels of somatic maintenance to keep the organism in sound condition during the normal expectation of life in the wild environment, but investments in maintenance at higher levels will be selected against. An example would be selection to optimise the levels of stress proteins mediating removal and/or refolding of denatured molecules within the cell; the corresponding targets of selection would be the genes that regulate stress protein expression.