Characterizing primary and secondary senescence in vivo

Area of Science:

• Cellular biology
• Aging research
• Molecular mechanisms of senescence

Background:

• Senescence can propagate in vitro via the senescence-associated secretory phenotype, inducing secondary senescence.
• The in vivo induction, regulation, and physiological roles of secondary senescence are not well understood.

Purpose of the Study:

• To generate and utilize senescence-inducible mouse models to map primary and secondary senescent cells in vivo.
• To investigate the tissue- and inducer-dependency of senescence phenotypes.
• To elucidate the molecular mechanisms and regulators of secondary senescence.

Main Methods:

• Generation of senescence-inducible mouse models expressing activated MEK1 or MKK6 and mCherry.
• Spatially resolved RNA expression analyses at the single-cell level.
• Investigation of interleukin-1β's role in inducing secondary senescence.

Main Results:

• Senescence phenotypes are highly tissue- and inducer-dependent.
• Single-cell RNA expression analysis reveals unique transcriptional profiles for each senescence induction, explaining in vivo heterogeneity.
• Interleukin-1β, mainly from macrophages, was identified as a key inducer of secondary senescence.

Conclusions:

• Primary and secondary senescence in vivo are distinct and context-dependent.
• Macrophage-derived interleukin-1β plays a critical role in driving secondary senescence.
• The developed mouse models provide valuable tools for studying and manipulating senescence in aging and disease.