AMPK alleviates oxidative stress‑induced premature senescence via inhibition of NF-κB/STAT3 axis-mediated positive...

Area of Science:

• Cellular senescence
• Molecular biology
• Inflammation research

Background:

• Stress-induced premature senescence (SIPS) involves the senescence-associated secretory phenotype (SASP).
• AMP-activated protein kinase (AMPK) is implicated in SIPS prevention, but its mechanisms regarding SASP are unclear.
• NF-κB and STAT3 signaling pathways are involved in senescence and SASP production.

Purpose of the Study:

• To elucidate the mechanisms by which AMPK affects SASP and SIPS.
• To investigate the interplay between NF-κB, STAT3, and SASP in oxidative stress-induced senescence.
• To determine if AMPK can inhibit the positive feedback loop involving NF-κB/STAT3 and SASP.

Main Methods:

• Induction of SIPS using oxidative stress.
• Treatment with NF-κB and STAT3 inhibitors.
• Analysis of conditioned medium from senescent cells.
• Assessment of AMPK's regulatory role in the NF-κB/STAT3/SASP pathway.

Main Results:

• SIPS involves dynamic NF-κB activation, driving SASP production and amplifying STAT3 signaling.
• NF-κB and STAT3 inhibitors reduced oxidative stress-induced senescence.
• Conditioned medium from senescent cells induced senescence in healthy cells, an effect blunted by a STAT3 inhibitor.
• AMPK was confirmed to negatively regulate SASP production and senescence via inhibition of the NF-κB/STAT3 pathway.

Conclusions:

• AMPK prevents oxidative stress-induced senescence.
• AMPK acts by inhibiting the positive feedback loop mediated by NF-κB/SASP/STAT3 signaling.
• Targeting the NF-κB/SASP/STAT3 pathway offers a potential therapeutic strategy for senescence-related conditions.