The survival of cells critically depends on the sensing and response to a variety of stresses, and cells possess several control mechanisms to manage stress responses. Stress often leads to the formation of cytoplasmic RNA–protein complexes – the stress granules (SGs) – but their exact biological role remains unclear. A number of factors are involved in cellular stress responses; they include sirtuins (SIRTs), a family of conserved protein deacetylases that regulate diverse cellular processes including ageing. SIRT6 has been described to regulate the expression of a high number of stress-responsive and metabolism-related genes in the nucleus, and most of the functions of SIRT6 seem linked to its chromatin-modifying activities. On page 5166, Monika Jedrusik-Bode, Eva Bober and colleagues now investigate the role of SIRT6 and of its C. elegans homologue SIR-2.4 in the formation and function of stress granules. They find that, under stress, SIRT6 translocates to the cytosol, where it facilitates SG assembly through the dephosphorylation of the SG component G3BP, as well as SG disassembly during stress recovery. Similarly, the authors observe that SIR-2.4 is necessary for the efficient formation of P granules and extended survival under heat stress. Taken together, these results point to a new, evolutionary conserved, function of SIRT6 in stress protection that might also link cellular stresses and aging, because SG formation – as an important cell survival mechanism – is known to be impaired with increasing age.