Reversal of laminopathies: the curious case of SUN1

Mutations in the LMNA gene are associated with a spectrum of human dystrophic diseases termed the nuclear laminopathies. We recently found that the accumulation of the inner nuclear envelope proteins SUN 1 is pathogenic in progeric and dystrophic laminopathies. This conclusion arose from the unexpected observation that the deletion of Sun1, instead of accelerating aging, actually ameliorated the progeric and dystrophic phenotypes in Lmna-deficient mice. In human cells, knocking down SUN 1 corrected the nuclear aberrancies and the senescent tendencies of HGPS (Hutchinson-Gilford progeria syndrome) skin fibroblasts. Here we offer additional comments on the contributions of SUN 1 and the process of normal protein turnover to cellular aging.