Mitochondrial dysfunctions play major roles in ageing. How mitochondrial stresses invoke downstream responses and how specificity of the signaling is achieved, however, remains unclear. We have previously discovered that the RNA component of Telomerase
is imported into mitochondria, processed to a shorter form
, and then exported back to the cytosol. Cytosolic
levels respond to mitochondrial functions, but have no direct effect on these functions, suggesting that cytosolic
functions downstream of mitochondria as a signal of mitochondrial functions. Here, we show that cytosolic
plays a regulatory role on cellular senescence and is involved in cognition decline in 10 months old mice, independent of its telomerase function. Manipulation of cytosolic
levels affects cellular senescence and cognition decline in 10 months old mouse hippocampi without affecting telomerase activity, and most importantly, affects cellular senescence in
cells. These findings uncover a senescence-related regulatory pathway with a non-coding RNA as the signal in mammals.
Electronic supplementary material
The online version of this article (10.1007/s13238-019-0612-5) contains supplementary material, which is available to authorized users.