Reversal of Cognitive Aging in Old Mice

The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 6 No. 5 • November-December 2003

Reversal of Cognitive Aging in Old Mice and Cognitive Dysfunction from Alcohol in Young Mice

There is much similarity between mice and men; in fact, there is about an 85% sharing of genes between the two species. Models of cognitive aging include aged mice and alcohol-intoxicated young mice; in both of these models, memory is impaired. A new study1 reports that the flavonoid quercetin administered chronically at doses of 10, 25, and 50 mg/kg for 30 days or coadministered with alcohol (15% w/v, 2 g/kg per day orally) for 24 days significantly reversed the age-related or chronic ethanol-induced retention deficits in two paradigms (one-trail step-down passive avoidance and elevated-plus maze).

Chronic administration of quercetin for 30 days also reversed age-associated increases in TBARS (caused by lipid peroxidation) and decline in forebrain total glutathione (GSH), superoxide dismutase (SOD), and catalase levels. Chronic alcohol administration in the young mice caused increased TBARS and reduction in forebrain GSH, SOD, and catalase, significantly reversed by coadministration of quercetin (10, 25, and 50 mg/kg). The authors propose that these effects are due to the antioxidant properties of quercetin.

Quercetin also has many effects on signaling pathways, though we do not know which ones might have been involved in these cognition-enhancing effects. For example, quercetin glucuronide (a metabolite of quercetin) prevented hypertrophy of vascular smooth muscle cells (part of the atherosclerotic process) caused by angiotensin II by inhibiting c-Jun N-terminal kinase (JNK) and AP-1 (activator protein-1).2 Quercetin also protected human lung cells from cooking-oil fumes by inhibiting cyclooxygenase-2 (COX-2) expression by altering the NF-kappaB pathway.3 Good dietary sources of quercetin include onions, green tea, and bilberry; there are many others. It is also available in the form of supplements.

  1. Singh et al. Reversal of aging and chronic ethanol-induced cognitive dysfunction by quercetin, a bioflavonoid. Free Rad Res 37(11):1245-52 (2003).
  2. Yoshizumi et al. Quercetin glucuronide prevents VSMC hypertrophy by angiotensin II via the inhibition of JNK and AP-1 signaling pathways. Biochem Biophys Res Comm 293:1458-65 (2002).
  3. Lin et al. Protection by quercetin against cooking oil fumes-induced DNA damage in human lung adenocarcinoma CL-3 cells: role of COX-2. Nutr Cancer 44(1):95-101 (2002).

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