Nicotinamide Mononucleotide Ameliorates Cellular Senescence and Inflammation Caused by Sodium Iodate in RPE

Area of Science:

• Cellular senescence
• Age-related macular degeneration (AMD)
• Retinal pigment epithelium (RPE) biology
• NAD+ metabolism

Background:

• Senescent cells exhibit reduced NAD+ levels and contribute to age-related diseases like AMD.
• Sodium iodate (NaIO3) is a model oxidant for dry AMD, known to induce retinal senescence.
• The precise role of NaIO3 and its mechanism in inducing RPE senescence were previously unclear.

Purpose of the Study:

• To investigate the role of NaIO3 in inducing RPE senescence.
• To elucidate the underlying mechanisms of NaIO3-induced RPE senescence.
• To evaluate the therapeutic potential of N-acetylcysteine (NAC) and nicotinamide mononucleotide (NMN) in ameliorating RPE senescence.

Main Methods:

• Induction of RPE senescence using NaIO3 in vitro.
• Assessment of senescence markers (SA-β-gal, p16, p21), oxidative stress, NAD+ levels, DNA damage, and mitochondrial function.
• Treatment with NAC and NMN to evaluate their effects on senescent RPE cells and in vivo models.

Main Results:

• NaIO3 treatment increased SA-β-gal, p16, and p21 levels, indicating RPE senescence.
• Senescent RPE cells exhibited oxidative stress, NAD+ depletion, DNA damage, and mitochondrial dysfunction.
• NMN significantly ameliorated RPE senescence, DNA damage, and mitochondrial dysfunction, while NAC showed minimal effect. NMN's benefits were linked to Sirt1 signaling.

Conclusions:

• NaIO3-induced RPE senescence shares key features with AMD.
• NMN effectively counteracts RPE senescence and associated changes by restoring NAD+ levels and mitochondrial function.
• NMN shows potential as a therapeutic agent for RPE senescence and pre-AMD conditions.