A comparative study of anti-aging properties and mechanism: resveratrol and caloric restriction

Juan Li, Chun-Xia Zhang, Yi-Mei Liu, Ke-Li Chen, Gang Chen, Juan Li, Chun-Xia Zhang, Yi-Mei Liu, Ke-Li Chen, Gang Chen

Abstract

Resveratrol and caloric restriction (CR) are the powerful therapeutic options for anti-aging. Here, their comparative effect on longevity-associated gene silencing information regulator (SIRT1) were evaluated in vitro and in vivo. IMR-90 cells treated with 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) were applied to establish a cellular senescence model, and rats treated with D-galactose (D-gal) were used as an aging animal model. Resveratrol and CR exhibited similar anti-aging activities, evidenced by inhibiting senescence and apoptosis, and restoring cognitive impairment and oxidative damage. Moreover, they could up-regulate telomerase (TE) activity, increase expressions of SIRT1, forkhead box 3a (Foxo3a), active regulator of SIRT1 (AROS) and Hu antigen R (HuR ), but decrease p53 and deleted in breast cancer 1 (DBC1) levels. However, 10 μM resveratrol in vitro and the high dose group in vivo showed relatively stronger activities of anti-aging and stimulating SIRT1 level than CR. In conclusion, resveratrol and CR showed similar anti-aging activities on SIRT1 signaling, implicating the potential of resveratrol as a CR mimetic.

Keywords: SIRT1; aging; caloric restriction; resveratrol.

Conflict of interest statement

CONFLICTS OF INTEREST No conflict of interest from all participating authors.

Figures

Figure 1. Resveratrol and caloric restriction decreases…
Figure 1. Resveratrol and caloric restriction decreases SA-β-gal staining in AAPH-treated IMR-90 cells
AAPH induced IMR-90 cells were treated with caloric restriction (CR) or resveratrol (RES) at the indicated concentration for 2 days. The magnification was 20×.
Figure 2. Scanning electron microscopy analysis of…
Figure 2. Scanning electron microscopy analysis of IMR-90 cells
AAPH induced IMR-90 cells were treated with caloric restriction (CR) or resveratrol (RES) at the indicated concentration for 2 days. The magnification was 6000×.
Figure 3. Resveratrol (RES) and caloric restriction…
Figure 3. Resveratrol (RES) and caloric restriction (CR) decreased apoptosis in AAPH-treated IMR-90 cells
Cells were stained with Annexin V-FITC/PI and analyzed by flow cytometry. The FL1 channel was used to detect annexin-V-FITC staining and the FL2 channel was for PI staining.
Figure 4. Effect of resveratrol and caloric…
Figure 4. Effect of resveratrol and caloric restriction on the body weight of D-gal treated rats during the experiment
All values were expressed as means ± SD. NG, negative control group; MG, model control group; RESL, low dose of resveratrol group; RESH, high dose of resveratrol group; CR, caloric restriction group.
Figure 5. Effect of resveratrol and caloric…
Figure 5. Effect of resveratrol and caloric restriction on the behavior of D-gal treated rats with Morris water maze
(A) Comparison of latencies to platform during 4 training days. Each mouse was subjected to 4 trials per day. (B) Comparison of swimming speed during 4 training days. (C) Comparison of numbers of crossing over platform where the platform was removed for probe trial. (D) The typical swimming track in probe trial. All values were expressed as means ± SD. *P < 0.05, **P < 0.01 compared with negative control group; #P < 0.05, ##P < 0.01 compared with model control group. NG, negative control group; MG, model control group; RESL, low dose of resveratrol group; RESH, high dose of resveratrol group; CR, caloric restriction group.
Figure 6. Effect of resveratrol and caloric…
Figure 6. Effect of resveratrol and caloric restriction on lipofuscin level of aging rats
All values were expressed as means ± SD. *P < 0.05 compared with negative control group; #P < 0.05 compared with model control group. NG, negative control group; MG, model control group; RESL, low dose of resveratrol group; RESH, high dose of resveratrol group; CR, caloric restriction group.
Figure 7. Effect of resveratrol and caloric…
Figure 7. Effect of resveratrol and caloric restriction on the TE activity in aging rats
All values were expressed as means ± SD. *P < 0.05 compared with control group; #P < 0.05 compared with model group. NG, negative control group; MG, model control group; RESL, low dose of resveratrol group; RESH, high dose of resveratrol group; CR, caloric restriction group; TE, telomerase.
Figure 8. Effect of resveratrol (RES) and…
Figure 8. Effect of resveratrol (RES) and caloric restriction (CR) on SIRT1 mRNA expression in IMR-90 cells
All values were expressed as means ± SD. **P < 0.01 compared with negative control group; ##P < 0.01 compared with model control group.
Figure 9
Figure 9
(A) Effect of resveratrol and caloric restriction on mRNA expressions of SIRT1, p53 and Foxo3a in brains of aging rats. (B) Effect of resveratrol and caloric restriction on mRNA expressions of SIRT1, p53 and Foxo3a in livers of aging rats. All values were expressed as means ± SD. *P < 0.05, **P < 0.01 compared with negative control group; #P < 0.05, ##P < 0.01 compared with model control group; #P<0.05, ##P<0.01 compared with CR group (RES group). NG, negative control group; MG, model control group; RESL, low dose of resveratrol group; RESH, high dose of resveratrol group; CR, caloric restriction group.
Figure 10. Effect of resveratrol and caloric…
Figure 10. Effect of resveratrol and caloric restriction on protein expressions of p53, FOXO3a, HuR, AROS and DBC1 in brains of aging rats
All values were expressed as means ± SD. *P < 0.05, **P < 0.01 compared with negative control group; #P < 0.05, ##P < 0.01 compared with model negative group; ∆P < 0.05 compared with CR group (RES group). NG, negative control group; MG, model control group; RESL, low dose of resveratrol group; RESH, high dose of resveratrol group; CR, caloric restriction group.
Figure 11. Immunohistochemical analysis of p53 (A,…
Figure 11. Immunohistochemical analysis of p53 (A, B) and FOXO3a (C, D) expressions in liver (A, C) and brain (B, D) tissues of aging rats
The magnification was 20×. NG, negative control group; MG, model control group; RESL, low dose of resveratrol group; RESH, high dose of resveratrol group; CR, caloric restriction group.

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