Short In Vivo Reprogramming Treatment Reverses Age-Related Omics Changes in Mice

Researchers here demonstrate that, in mice, many biological markers of aging (in the epigenome, transcriptome, and metabolome) are made more youthful by a short in vivo exposure to the Yamanaka factors capable of reprogramming cells into induced pluripotent stem cells. That process also resets epigenetic marks on the genome to a youthful configuration, improving mitochondrial function, among other benefits. In this case, the goal of a short treatment is to minimize any possible cell conversion, keeping the reprogramming exposure short enough to only change epigenetic markers, gene expression, and cell behavior to be more youthful. The primary challenge in bringing this class of therapy to the clinic will be the long-term safety questions, how to assess (and then minimize) the risk of cancer via unwanted pluripotency of cells, when the consequences of that risk might take years to become visible in humans. The expression of the pluripotency factors OCT4, SOX2, KLF4 and MYC (OSKM) can convert somatic differentiated cells into pluripotent stem cells in a process known as reprogramming. Notably, cycles of brief OSKM expression do not change cell identity but can reverse markers of aging in cells and extend longevity in progeroid mice. However, little is known about the mechanisms involved. Here, we have studied changes in the DNA methylome, transcriptome and metabolome in naturally aged mice subject to a single period of transient OSKM expression. We used the repr...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs