ROS-Responsive H₂S Release Attenuates Renal Aging by Preserving Mitochondrial Function and Mitigating Oxidative...

Area of Science:

• Biochemistry
• Cell Biology
• Gerontology

Background:

• Cellular senescence, a state of irreversible cell cycle arrest, contributes to age-related functional decline and tissue damage.
• Oxidative stress, driven by reactive oxygen species (ROS), induces mitochondrial dysfunction and accelerates senescence.

Purpose of the Study:

• To design and synthesize a novel ROS-responsive compound, HS-N, capable of scavenging ROS and releasing hydrogen sulfide (H2S).
• To evaluate the efficacy of HS-N in attenuating cellular senescence and improving tissue function in vitro and in vivo.

Main Methods:

• Synthesis of HS-N, a ROS-responsive branched reductive compound.
• In vitro assays assessing HS-N's effects on stress-induced senescence and fibroblast migration.
• In vivo studies in aged mice involving HS-N administration and analysis of serum markers, gene expression, and histopathology.

Main Results:

• HS-N effectively scavenged ROS and released H2S, converting a toxic stimulus into a beneficial signal.
• HS-N attenuated stress-induced senescence, preserved mitochondrial function, and restored fibroblast migratory capacity.
• In aged mice, HS-N administration reduced serum urea and IL-1β, decreased renal NOX4 expression, and attenuated glomerular hypertrophy without major organ toxicity.

Conclusions:

• HS-N alleviates senescence by stabilizing mitochondrial function and modulating redox-linked inflammatory signaling.
• The "turn poison into medicine" strategy using ROS-triggered H2S release offers a promising framework for combating age-related diseases.