Stem cells for all ages, yet hostage to aging

In a tour de force, Rusty Gage and colleagues (1) showed that aging transcriptional changes in fibroblasts (FB) were reversed in induced pluripotent stem cells (iPSCs) derived from donors across the lifespan. Subsequently, when iPSCs were induced to form neurons by direct induction (iNS), the aging transcriptional signature was also absent. In contrast, when aging FBs were directly programmed to iNS by a similar protocol, they maintained an aging transcriptional signature. Remarkably, much of this signature was not the original signature of the FBs but a new age-associated signature more closely allied to neural related gene action. Thus, FB-derived iNS retained an “aging state” on direct cell programming, but not a hard wired, age-related transcriptional signature.