Three papers published this past Sunday touch upon different aspects of the aging problem. The first one appeared in Nature and is authored by Rui Yi and colleagues, who found that microRNA-203 promotes the differentiation of skin stem cells by repressing “stemness”. In stratified epithelia, stem cells located basally are crucial for self renewal. As these cells leave the basal zone, they differentiate and cease to behave like stem cells. What the authors found is that microRNA-203 is crucial for this differentiation process, leading the stem cells to exit the cell cycle. Mechanistically, this effect depends on repression of p63 expression, a molecule that had previously been shown to regulate stem-cell maintenance in epithelia.

The second one is on one of my favorite topics — progeria. Writing in Nature Cell Biology, Paola Scaffidi and Tom Misteli report that expression of mutant lamin-A, the molecule that causes Hutchinson-Gilford Progeria Syndrome (HGPS), interferes with the function of human mesenchymal stem cells (hMSCs) by promoting the activation of downstream

effectors of Notch, affecting the differentiation potential of hMSCs. The in vivo relevance of these results to HGPS and to normal aging remains to be established, but the possibility is indeed tantalizing.

The third one is a Brief Communication in Nature Genetics. In it, Marc Vermulst and his colleagues establish a link between mitochondrial DNA (mtDNA) deletions and aging in the so-called Polga mice, which harbor a proofreading-deficient copy of polymerase gamma and are characterized by premature aging. They found that the rate at which different tissues accumulate mtDNA mutations before they reach phenotypic expression differs profoundly — brain, heart and gut are among the most affected parts of the body. The question remains, though, if these mtDNA mutations are also relevant during normal aging in wild-type mice and, of course, in humans.