Protein synthesis and aging: eIF4E and the soma vs. germline distinction

Classic studies in diverse organisms, including humans, have demonstrated that aging is accompanied by marked alterations in both general and specific protein synthesis. These early observations established a link between the aging process and the regulation of protein synthesis. However, two important questions remained. First, what are the molecular mechanisms underlying the changes in protein synthesis during aging? Second, are these changes simply a consequence of aging or do they actually have a causative role in senescent decline? We have recently shown that elimination of a specific isoform of the eukaryotic mRNA translation initiation factor 4E (eIF4E) that functions in somatic cells, reduces protein synthesis and extends lifespan in the nematode Caenorhabditis elegans. Depletion of eIF4E in the soma extends lifespan via a mechanism independent of the insulin/IGF pathway that modulates aging in diverse species. Our findings suggest that regulation of protein synthesis is an important determinant of longevity and provide a framework for elucidating the mechanisms by which the rate of protein synthesis influences the process of aging.