Multiorgan transcriptomics and circulating extracellular vesicle profiling reveal age-dependent systemic...

Area of Science:

• Gerontology
• Anesthesiology
• Molecular Biology
• Systems Biology

Background:

• Elderly patients are more prone to postoperative complications after general anesthesia and surgery.
• The molecular mechanisms underlying age-dependent vulnerability to anesthesia and surgery are not well understood.

Purpose of the Study:

• To investigate the age-dependent transcriptional responses in multiple tissues following anesthesia and surgery.
• To identify molecular pathways and biological processes affected by perioperative stress in aging mice.

Main Methods:

• RNA sequencing was performed on olfactory bulb, hippocampus, lung, and spleen from young, late middle-aged, and geriatric male mice.
• Mice were exposed to isoflurane anesthesia and laparotomy (ISO/OP) for 2 hours.
• Transcriptional profiles were analyzed 24 hours post-exposure.

Main Results:

• Short-term ISO/OP induced significant age-dependent transcriptional changes across all examined tissues.
• Late middle-aged mice showed activated stress and metabolism pathways in the brain, with suppressed maintenance programs.
• Peripheral organs in late middle-aged mice exhibited amplified immune/inflammatory signaling and suppressed homeostatic programs.
• Extracellular vesicles mirrored tissue shifts, indicating a systemic transition towards stress and immune dominance by late middle-age.
• Geriatric mice displayed unique stress, detoxification, and circadian gene expression patterns, with altered EV cargo.

Conclusions:

• Late middle-age represents a period of amplified biological reactivity to perioperative stress across central and peripheral systems.
• These findings suggest a critical window for perioperative risk stratification and preventative interventions in aging populations.
• Age-dependent molecular remodeling following anesthesia and surgery impacts multiple organ systems and systemic signaling.