Table 1.

Impact of caloric restriction on age-associated microRNAs (miRNAs) changes and histones modifications.

Study	Model	Intervention	Biological Matrix/Tissue	Impact of Intervention
miRNAs
Khanna et al. 2011 [63]	Mice	CR mice in three age groups: 12, 24, and 28 months.	Brain	Under CR, no age-dependent up-regulation of miR-181a-1*, miR-30e, and miR-34a, as observed in AL fed animals, associated with a gain in the expression of their target gene Bcl-2.
Mercken et al. 2013 [65]	Rhesus monkeys (all males)	Animals maintained on CR diet (TestDiet® #5L1F, Purina Mills) most of their lives (20.8–22.6 years).	Skeletal muscle	CR was able to reverse the age-related alterations in miRNA expression.
Dhahbi et al. 2013 [66]	Mice (B6C3F1 strain)	CR (<40% fewer calories than the control group) from 1 month until 27 months of age.	Serum	CR antagonized the increase in serum levels of a large set of miRNAs.
Wood et al. 2015 [35]	Rats	55% CR until sacrifice (6, 12, or 28 months).	Cerebral cortex	Significant overexpression of miR-98-3p in all groups of CR rats.
Histones modifications
Li et al. 2011 [75]	Normal diploid WI-38, MRC-5 and IMR-90 human fetal lung fibroblasts	Glucose restriction (glucose- and pyruvate-free DMEM medium)	NA	Activation of SIRT1 by glucose restriction led to chromatin remodeling of the p16INK4a gene promoter and a decreased expression of this gene, ultimately associated with the inhibition of cellular senescence.
Chouliaras et al. 2013 [77]	Mice (males) (C57Bl6J wild-type strain and transgenic animals overexpressing SOD1)	50% CR until sacrifice (12 or 24 months).	Hippocampus	CR prevented the age-related increase in histone deacetylase 2 (HDAC2) levels.
Molina-Seranno et al. 2016 [78]	Yeast (Saccharomyces cerevisiae)	Reduction of glucose concentration in growth media from 2 to 0.1%.	NA	CR was associated with a reduction of histone H4 N-terminal acetylation.

CR: caloric restriction; AL: ad-libidum; NA: not applicable.