In vivo transcriptomic profiling using cell encapsulation identifies effector pathways of systemic aging

Area of Science:

• Gerontology
• Cellular Biology
• Biotechnology

Background:

• Systemic aging rejuvenates organisms, but isolating circulating factor effects on specific cells is challenging.
• Tissue complexity hinders understanding of long-range signaling in aging.

Purpose of the Study:

• To develop a method for profiling systemic aging effects on skeletal muscle progenitors independent of local tissue interactions.
• To accurately characterize effector pathways of systemic aging in vivo.

Main Methods:

• Encapsulation of human and mouse skeletal muscle progenitors in diffusible polyethersulfone hollow fiber capsules.
• In vivo transcriptomic profiling of encapsulated cells in young and old systemic environments.
• Comparison with in vitro serum profiling.

Main Results:

• Circulating factors in old environments activate Myc and E2F transcription factors.
• Systemic aging induces senescence and suppresses myogenic differentiation in skeletal muscle progenitors.
• In vitro serum profiling does not fully capture in vivo aging pathways.

Conclusions:

• In vivo cell encapsulation is a powerful tool for studying systemic aging.
• This method accurately identifies effector pathways of aging in specific cell populations.
• Understanding these pathways is crucial for developing rejuvenation strategies.