Abstract
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 observed that circulating long-range signaling factors in the old systemic environment lead to an activation of Myc and E2F transcription factors, induce senescence, and suppress myogenic differentiation. Importantly, in vitro profiling using young and old serum in 2D culture does not capture all pathways deregulated in encapsulated cells in aged mice. Thus, in vivo transcriptomic profiling using cell encapsulation allows for the characterization of effector pathways of systemic aging with unparalleled accuracy.
Highlights
In order to maximize the number of encapsulated cells and, at the same time, allow for adequate oxygen diffusion throughout the capsule, we selected a tubular hollow fiber membrane (HFM) with an outer diameter of 0.9 mm and an inner diameter of 0.7 mm (Fig. 1b)
Trypsinized hskMPs or mouse derived skeletal muscle progenitors (mskMPs) mixed with Matrigel were injected into the capsule trough the adaptor hub and the loaded capsule was transferred onto a 3D printed autoclavable USP Class VI plastic cutting and sealing platform (Figure 1-figure supplement 1e,f)
The effects of aged serum on cells in 2D culture only partially overlapped with our observations in encapsulated cells in young and old mice
Summary
Systemic crosstalk between tissues has emerged as an important determinant of organismal aging (Demontis et al, 2013) Supporting this notion, several features of tissue aging can be slowed or reversed by heterochronic parabiosis (Bert, 1864; Conboy et al, 2015). The positive effects of young blood on aged tissues appear to be milder than the pronounced negative effects of aged blood on young tissues (Rebo et al, 2016). This observation suggests the presence of dominant proaging factors in the systemic circulation, which cross-talk with local tissue niches to induce the global decline in organ function associated with old age. Recent studies have aimed at identifying the circulating factors involved in systemic aging, and some of the experimental interpretations have led to considerable controversy in the field (Conese et al, 2017)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
