Table 3.

Effects and mechanisms of resveratrol on aging.

Study type	Subjects	Administration methods	Dose & duration	Effects and mechanisms	Ref.
The suppression of oxidative stress
In vitro	Human erythrocytes	Cell culture	0.1–100 μM	Activated the plasma membrane redox system and ascorbate-free radical reductase, protected against lipid peroxidation and protein carbonylation, and restored the cellular redox homeostasis	[78]
In vitro	Immortalized lymphocytes	Cell culture	10 and 50 μM	Reduced the generation of ROS, upregulated the gene expression of antioxidants and antiaging factors	[79]
In vivo	F2 four-way cross-hybrid mice	Drinking water	14.09 mg/L for 6 or 12 months	Reversed oxidative damage but might result in nephrotoxicity	[80]
In vivo	Male grey mouse lemur	Diet supplement	200 mg/kg for 3-21 months	Ameliorated oxidative stress with age increase	[81]
In vivo	Male C57BL/6J mice	Drinking water	500 μg/animal for 6 months	Retarded the impact of aging and sustained high activities of GSH, GPx, and GSH transferase activities	[82]
In vivo	Male Wistar rats	Oral administration	10 mg/kg for 2-8 months	Decreased the level of NO and retarded the lipoperoxidation in the cardiac tissue	[83]
In vivo	C57BL/6 mice	Diet supplement	0.05% for 10 days	Blunted the exercise-induced increase in xanthine oxidase activity in muscles, lower H2O2, and Nox4 protein levels, increased the ratio of reduced GSH to oxidized GSH, prevented the increase in lipid oxidation, increased CAT and SOD activities	[112]
In vivo	Young and aged rats	Perfusion	NA	Ameliorated H2O2-induced oxidative stimulus in both young and aged rat brains and ameliorated basal oxidative stress in aged rat brains	[113]
In vivo	Aged C57BL/6 mice	Oral administration	30 mg/kg	Ameliorating renal oxidative stress via the Sirt1-mediated klotho expression	[114]
The inhibition of inflammation
In vitro	Vascular smooth muscle cells	Cell culture	1 μM	Reduced the secretion of IL-1β, IL-8, TNF-α, and MCP-1, decreased the production of O2·- in mitochondria, and upregulated the transcriptional activity of Nrf2	[86]
In vitro	Hippocampal astrocyte	Cell culture	10 μM	Decreased proinflammatory cytokines IL-1β and TNF-α and increased antioxidant defenses	[87]
In vivo	Male BALB/c mice	Diet supplement	0.4% for 4 weeks	Mitigated inflammatory response and cognitive deficits and reduced the increase of IL-1β in plasma and the IL-1β mRNA in the hippocampus	[88]
In vivo	Female C57BL/6 mice	Diet supplement	4 g/kg for 12 months	Reduced age-associated inflammation independently of PGC-1α	[89]
In vivo	Aged female mice	Oral gavage	0.1 mg/kg for 10 days	Attenuated peripheral and brain inflammation and ischemic brain injury	[115]
In vivo	Male C57BL/6J mice	Diet supplement	1 g/kg, W/W	Reduced the inflammation and cognitive disturbances induced by metabolic stress	[90]
The improvement of mitochondrial function
In vitro	Oocytes and granulosa cells	Cell culture	20 μM	Affected both oocytes and granulosa and improved the quality of oocytes through upregulation of mitochondrial biogenesis and degradation	[94]
In vivo	Aged mice	Oral gavage	15 mg/kg for 4 weeks	Improved physical endurance and oxidative stress via the regulation of mitochondrial biogenesis and function	[50]
In vivo	Female ICR mice	Intraperitoneal injection	50 mg/kg BW	Improved mitochondrial function, alleviated oxidative stress, and prevented apoptosis	[95]
In vivo	Aged zebrafish	Administration	20 mg/L	Promoted mitochondrial function and downregulated Akt/mTOR pathway activity	[17]
The regulation of apoptosis
In vivo	Aged Sprague-Dawley rats	Intraperitoneal injection	100 mg/kg for 7 days	Modified the performance of learning and memory, suppressed neuronal apoptosis	[67]
In vivo	Aged senescence-accelerated mice	Drinking water	5 mg/kg	Modulated the inflammatory, oxidative, and apoptotic status related to aging	[16]
In vivo, in vitro	Male albino Wistar rats; human diploid fibroblast strain	Oral administration	50, 100 mg/kg	Displayed antiaging activities by inhibiting senescence and apoptosis and recovering cognitive impairment and oxidative damage	[98]
In vitro	Mouse neuronal N2a cells	Cell culture	1.5 to 25 μM	Counteracted apoptosis, autophagy, and oxidative stress, associated with mitochondrial and peroxisomal dysfunction induced by 7-Ketocholesterol	[116]
In vivo	Sprague-Dawley rats	Oral gavage	80 mg/kg	Decreased apoptotic index, improved mitochondrial function, and inhibited oxidative stress	[99]
In vivo	Senescence-accelerated mice	Diet supplement	4.9 mg/kg for 8 months	Improved exercise capacity and voluntary motor behavior, increased the protein expression of antiapoptotic Bcl2	[100]
In vivo	Male senescence-accelerated mice	Intraperitoneal injection	20 mg/kg/day for 3 days	Attenuated the doxorubicin-induced elevations of apoptotic and catabolic markers measured as Bax, caspase 3 activity, apoptotic DNA fragmentation, ubiquitinated proteins, and proteasomal activity in aged muscles	[117]

Note: ROS: reactive oxygen species; GSH: glutathione; GPx: glutathione peroxidase; NO: nitric oxide; Nox4: NADPH oxidase 4; CAT: catalase; SOD: superoxide dismutase; Sirt1: sirtuin1; IL: interleukin; TNF-α: tumor necrosis factor-α; MCP-1: monocyte chemoattractant protein-1; Nrf2: nuclear factor erythroid-2 related factor 2; PGC-1α: peroxisome proliferator-activated receptor-γ coactivator-1α; Bcl2: B-cell lymphoma-2; Bax: BCL2-associated X.