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. 2021 Jan 15;13(1):232.
doi: 10.3390/nu13010232.

Effects of Late-Life Caloric Restriction on Age-Related Alterations in the Rat Cortex and Hippocampus

Claudia Tonini  1 , Marco Segatto  2 , Francesca Martino  1 , Luisa Cigliano  3 , Martina Nazzaro  3 , Laura Barberio  4 , Maurizio Mandalà  4 , Valentina Pallottini  1   5
Affiliations

Effects of Late-Life Caloric Restriction on Age-Related Alterations in the Rat Cortex and Hippocampus

Claudia Tonini et al. Nutrients. .

Abstract

Background: A major problem of aging is the disruption of metabolic homeostasis. This is particularly relevant in the brain where it provokes neurodegeneration. Caloric restriction is a physiologic intervention known to delay the deleterious consequences of aging in several species ranging from yeast to mammals. To date, most studies on experimental models have started this dietary intervention from weaning, which is very difficult to be translated to human beings. Here, we study the effects of a more realistic dietary regimen in rats, starting at an advanced age and lasting for six months.

Methods: we analyzed in the cortex and hippocampus, the proteins involved in the energetic balance of the cells, cholesterol metabolism, oxidative stress response, inflammation, synaptic impairment, and brain trophism.

Results: our results suggest that caloric restriction in late life can revert only some age-related changes studied here.

Keywords: aging; caloric restriction; cholesterol; cortex; hippocampus; rats.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Impact of aging and reduction of caloric intake (CR) on phosphorylated AMPK levels in the rat cortex and hippocampus. Representative Western blots and densitometric analyses of phosphorylated AMPK (P-AMPK) in cortex (a) and hippocampus (b), using vinculin as housekeeping protein for loading control. 3M (3-month-old rats); 24M (24-month-old rats); ND (normal diet); CR (caloric intake reduced by 40% for the last six months of life). Statistical analysis was performed by using one-way ANOVA followed by Tukey’s post hoc test. **** p < 0.0001, *** p < 0.001 vs. ND 3M; ## p < 0.01 vs. ND 24M.
Figure 2
Figure 2
Impact of age and CR on proteins handling cholesterol metabolism in rat cortex and hippocampus. Panels (a,b) show representative Western blots and densitometric analyses of HMGCR (total and phosphorylated protein) in the cortex and hippocampus, respectively. Panel c and d show representative Western blots and densitometric analysis of other proteins involved in cholesterol homeostasis in the cortex and hippocampus, respectively. 3M (3-month-old rats); 24M (24-month-old rats); ND (normal diet); CR (caloric intake reduced by 40% for the last 6 months of life). Protein levels were normalized to tubulin (a,b) and to vinculin (c,d). Statistical analysis was performed by using one-way ANOVA followed by Tukey’s post hoc test. ** p < 0.01 vs. ND3M ND; # p < 0.05 vs. 24M ND.
Figure 3
Figure 3
Impact of age and CR on membrane-bound and total levels of HRas and RhoA in rat cortex. Representative Western blots and densitometric analysis of membrane-bound (m-) and total content (t-) of HRas (a) and RhoA (b) in rat cortex. Vinculin and caveolin served as housekeeping proteins to normalize protein loading. 3M (3-month-old rats); 24M (24-month-old rats); ND (normal diet); CR (caloric intake reduced by 40% for the last 6 months of life). Statistical analysis was performed by using one-way ANOVA followed by Tukey’s post hoc test. * = p < 0.05, *** = p < 0.001, vs. 3M ND.
Figure 4
Figure 4
Impact of age and CR on the microglia marker Iba1 in rat cortex and hippocampus. Representative Western blots and densitometric analysis of Iba1 levels in the cortex (a) and hippocampus (b) normalized to vinculin. 3M (3-month-old rats); 24M (24-month-old rats); ND (normal diet); CR (caloric intake reduced by 40% for the last 6 months of life). Statistical analysis was performed by using one-way ANOVA followed by Tukey’s post hoc test. *** p < 0.001 vs. 3M ND; ## p < 0.01 vs. 24M ND.
Figure 5
Figure 5
Impact of age and CR on Nox2 and p47phox proteins in rat cortex and hippocampus. Representative Western blots and densitometric analyses of Nox2 and p47phox levels in the cortex (a) and hippocampus (b). Tubulin served as housekeeping protein to normalize protein loading. 3M (3-month-old rats); 24M (24-month-old rats); ND (normal diet); CR (caloric intake reduced by 40% for the last 6 months of life). Statistical analysis was performed by using one-way ANOVA followed by Tukey’s post hoc test. ** p < 0.01 vs. 3M ND, # p < 0.05; ## p < 0.01 vs. 24M ND.
Figure 6
Figure 6
No effect of age and CR on Synaptotagmin in rat cortex and hippocampus. Representative Western blots and densitometric analyses of synaptotagmin in the cortex (a) and hippocampus (b) normalized to actin levels as loading control. 3M (3-month-old rats); 24M (24-month-old rats); ND (normal diet); CR (caloric intake reduced by 40% for the last 6 months of life).
Figure 7
Figure 7
Impact of age and CR on levels of brain-derived neurotrophic factor (BDNF) and pro-BDNF in rat cortex and hippocampus. Representative Western blots and densitometric analyses of pro-BDNF and BDNF in the cortex (a) and hippocampus (b) normalized to vinculin. 3M (3-month-old rats); 24M (24-month-old rats); ND (normal diet); CR (caloric intake reduced by 40% for the last 6 months of life). Statistical analysis was performed by using one-way ANOVA followed by Tukey’s post hoc test. ** = p < 0.01 vs. ND3M.
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