Metabolic Stress Induces Cognitive Disturbances and Inflammation in Aged Mice: Protective Role of Resveratrol

Rejuvenation Res. 2017 Jun;20(3):202-217. doi: 10.1089/rej.2016.1885. Epub 2017 Jan 25.


Inflammation and oxidative stress (OS) are key points in age progression. Both processes impact negatively in cognition and in brain functions. Resveratrol (RV) has been postulated as a potent antioxidant natural compound, with rejuvenating properties. Inducing a metabolic stress by high-fat (HF) diet in aged C56/BL6 (24 months) led to cognitive disturbances compared with control age mated and with young mice. These changes were prevented by RV. Molecular determinations demonstrated a significant increase in some inflammatory parameters (TNF-α, Cxcl10, IL-1, IL-6, and Ccl3) in old mice, but slight changes in OS machinery. RV mainly induced the recovery of the metabolically stressed animals. The study of key markers involved in senescence and rejuvenation (mitochondrial biogenesis and Sirt1-AMPK-PGC1-α) demonstrated that RV is also able to modulate the changes in these cellular metabolic pathways. Moreover, changes of epigenetic marks (methylation and acetylation) that are depending on OS were demonstrated. On the whole, results showed the importance of integrative role of different cellular mechanisms in the deleterious effects of age in cognition and the beneficial role of RV. The work presented in this study showed a wide range of processes modified in old age and by metabolic stress, weighting the importance of each one and the role of RV as a possible strategy for fighting against.

Keywords: aging; behavior; cognition; metabolic stress; mitochondrial dynamics; neurodegeneration; resveratrol.

MeSH terms

  • 5-Methylcytosine / metabolism
  • Animals
  • Biomarkers / metabolism
  • Body Weight / drug effects
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / etiology*
  • Energy Intake / drug effects
  • Gene Expression Regulation / drug effects
  • Glucose Tolerance Test
  • Inflammation / complications
  • Inflammation / drug therapy*
  • Male
  • Maze Learning / drug effects
  • Memory / drug effects
  • Mice, Inbred C57BL
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Oxidative Phosphorylation / drug effects
  • Oxidative Stress / drug effects
  • Resveratrol
  • Stilbenes / pharmacology
  • Stilbenes / therapeutic use*
  • Stress, Physiological / drug effects*


  • Biomarkers
  • Neuroprotective Agents
  • Stilbenes
  • 5-Methylcytosine
  • Resveratrol