Sustained exposure to a young systemic environment rejuvenates aged organisms and promotes cellular function. However, due to the intrinsic complexity of tissues it remains challenging to pinpoint niche-independent effects of circulating factors on specific cell populations. Here we describe a method for the encapsulation of human and mouse skeletal muscle progenitors in diffusible polyethersulfone hollow fiber capsules that can be used to profile systemic aging in-vivo independent of heterogeneous short-range tissue interactions. We observe that circulating long-range signaling factors in the old systemic environment have dominant effects on inflammation related processes that act in concert with increased activity of Myc and E2F transcription factors. Importantly, this signature is conserved across species and a subset of processes altered in encapsulated progenitors, are also affected in brain tissue of heterochronic parabionts. Altogether, our study characterizes the cellular signature of systemic aging mediated by direct effects of long-range signaling factors and identifies conserved therapeutic targets for systemic rejuvenation.

In-vivo Transcriptomic Profiling of Systemic Aging using Cell Encapsulation