Table 3.

Interventions that modulate SIRT3 signaling in age-related neurodegenerative diseases.

Experimental Model	Intervention	The Effect of Intervention	Reference
In vitro: amyloid β oligomer-treated primary hippocampal neuronal cells In vivo: transgenic PS1V97L mouse model	Honokiol	Ameliorates mitochondrial dysfunction by activating SIRT3 and increasing its levels, which results in suppressed ROS, an increased ATP production, normalized mitochondrial membrane potential, delayed cognitive impairment; Decreases amyloid-β-induced hippocampal neuron apoptosis and improves cognitive performance.	[194] [195] [196]
DNA repair deficiency mouse (3xTgAD/Polβ+/−)	Nicotinamide riboside	Improves memory, learning and motor function; Decreases systemic inflammation, phosphorylated tau, DNA damage and apoptosis; Restores SIRT3 and SIRT6 levels; Restores synaptic plasticity in the hippocampus; Increases deacetylated SOD2 and increases neurogenesis; No effect on amyloid-β production.	[197]
In vitro and in vivo gentamicin-induced hair cell loss model	Adjudin	Protects against gentamicin-induced hair cell loss in rats’ cochleae by increasing SIRT3 mRNA and protein levels expression and decreasing ROS.	[198]
Noise-induced hearing loss mouse models	Nicotinamide riboside	Protects against degeneration of spiral ganglion neurites and noise-induced hearing loss in a SIRT3-dependent manner; Increases mitochondrial NAD+ and SIRT3 activity.	[199]
Four-week-old Sprague Dawley rats	d-Galactose-induced aging	Decreases SIRT3 expression, mtDNA lesions and SOD2 activity; Increases malondialdehyde and apoptosis levels in rats’ auditory cortices in natural and D-galactose-induced aging.	[200]
Peripheral lymphocytes from patients with AD	Resveratrol	AD patient lymphocytes show increased oxidative stress. Selenium administration did not modify the expression of SIRT3 or other longevity-related genes, but resveratrol upregulated SIRT3, SIRT1, SOD2 and NRF2 (a transcription factor that activates antioxidant response genes), that could be responsible for SIRT3 upregulation after resveratrol administration and provide protective effects in AD afflicted cells.	[201] [202] [203]