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. 2025 Mar 28;17(7):1187.
doi: 10.3390/nu17071187.

The Impact of Resveratrol and Melatonin on the Genome and Oxidative Status in Ageing Rats

Marko Gerić  1 , Lucia Nanić  2 , Vedran Micek  3 , Ivana Novak Jovanović  1 , Goran Gajski  1 , Dubravka Rašić  1 , Tatjana Orct  4 , Marija Ljubojević  1 , Dean Karaica  1 , Jasna Jurasović  3 , Ivana Vrhovac Madunić  1 , Maja Peraica  1 , Ivan Sabolić  1 , Vanessa Moraes de Andrade  5 , Davorka Breljak  1 , Ivica Rubelj  2
Affiliations

The Impact of Resveratrol and Melatonin on the Genome and Oxidative Status in Ageing Rats

Marko Gerić et al. Nutrients. .

Abstract

Background: Given the growing challenges posed by an ageing population, particularly in Western countries, we aimed to investigate the potential geroprotective effects of resveratrol and melatonin in ageing rats.

Methods: The animals were treated with these two compounds starting at 3 months of age and continuing until 1 year or 2 years of age. Using a multibiomarker approach, we assessed DNA damage, telomere length, and the oxidative status in their urine, liver, and kidneys.

Results: Despite employing this experimental approach, our results did not provide conclusive evidence of geroprotective effects across the evaluated organs. However, we observed sex-dependent differences in response to treatment.

Conclusions: Given the high potency of these two compounds, further research is warranted to explore their incorporation into daily routines as a strategy to mitigate ageing-related effects.

Keywords: DNA damage; ageing; melatonin; oxidative stress; resveratrol; telomeres.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
DNA damage results. DNA strand breaks in the liver (A–D) and kidney (E–H), along with urinary levels of 8-oxo-2′-deoxyguanosine (8-OHdG) (I–L), measured in ageing rats (1-year-old and 2-year-old, both sexes) treated with melatonin (MEL) or resveratrol (RSV). Blue bars represent male rats, while purple bars represent female rats. The first and third columns correspond to 1-year-old animals, whereas the second and fourth correspond to 2-year-old animals. No statistically significant differences were observed between the treated and control groups.
Figure 2
Figure 2
Average telomere length in the liver (A–D) and kidney (E–H) of ageing rats (1-year-old and 2-year-old, both sexes) treated with melatonin (MEL) or resveratrol (RSV). Blue bars represent male rats, while purple bars represent female rats. The first and third columns correspond to 1-year-old animals, whereas the second and fourth correspond to 2-year-old animals. * indicates significantly different (p < 0.05) compared to the control group.
Figure 3
Figure 3
Malondialdehyde (MDA) concentrations in the liver (A–D), kidney (E–H), and urine (I–L) of ageing rats (1-year-old and 2-year-old, both sexes) treated with melatonin (MEL) or resveratrol (RSV). Blue bars represent male rats, while purple bars represent female rats. The first and third columns correspond to 1-year-old animals, whereas the second and fourth correspond to 2-year-old animals. * indicates significantly different (p < 0.05) compared to the control group.
Figure 4
Figure 4
Protein carbonyl (PC) concentrations in the liver (A–D) and kidney (E–H) of ageing rats (1-year-old and 2-year-old, both sexes) treated with melatonin (MEL) or resveratrol (RSV). Blue bars represent male rats, while purple bars represent female rats. The first and third columns correspond to 1-year-old animals, whereas the second and fourth correspond to 2-year-old animals. * indicates significantly different (p < 0.05) compared to the control group.
Figure 5
Figure 5
Glutathione (GSH) concentrations in the liver (A–D) and kidney (E–H) of ageing rats (1-year-old and 2-year-old, both sexes) treated with melatonin (MEL) or resveratrol (RSV). Blue bars represent male rats, while purple bars represent female rats. The first and third columns correspond to 1-year-old animals, whereas the second and fourth correspond to 2-year-old animals. * indicates significantly different (p < 0.05) compared to the control group.
Figure 6
Figure 6
Glutathione peroxidase (GPx) activity in the liver (A–D) and kidney (E–H) of ageing rats (1-year-old and 2-year-old, both sexes) treated with melatonin (MEL) or resveratrol (RSV). Blue bars represent male rats, while purple bars represent female rats. The first and third columns correspond to 1-year-old animals, whereas the second and fourth correspond to 2-year-old animals. * indicates significantly different (p < 0.05) compared to the control group.
Figure 7
Figure 7
Superoxide dismutase (SOD) activity in the liver (A–D) and kidney (E–H) of ageing rats (1-year-old and 2-year-old, both sexes) treated with melatonin (MEL) or resveratrol (RSV). Blue bars represent male rats, while purple bars represent female rats. The first and third columns correspond to 1-year-old animals, whereas the second and fourth correspond to 2-year-old animals. No statistically significant differences were observed between the treated and control groups.
Figure 8
Figure 8
A study and sampling design. Starting at 3 months of age, rats were provided with ad libitum access to either a vehicle (0.1% v/v ethanol in tap water), melatonin (MEL; 10 mg/L vehicle), or resveratrol (RSV; 10 mg/L vehicle), continuing until they reached 12 or 24 months of age. Prior to sacrifice, the animals were weighed and housed in metabolic cages to assess liquid consumption and collect urine samples. Subsequently, liver, kidney, and urine samples were collected for the analyses of baseline DNA damage, telomere length, and oxidative stress biomarkers.
Figure 9
Figure 9
Chemical structures of melatonin ((A) IUPAC name N-[2-(5-methoxy-1H-indol-3-yl)ethyl]acetamide, CAS number 73-31-4) and resveratrol ((B) IUPAC name 5-[(E)-2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol, CAS number 501-36-0). Adapted from reference [65].
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