A 2005 study conducted by the National Institute of Aging (NIA) examined the effects of blueberry polyphenols on lifespan and aging of the nematode, Caenorhabditis elegans (C. elegans, a microscopic roundworm). A mixture of blueberry polyphenols increased lifespan and slowed aging-related declines in C. elegans. The blueberry extract consists of three major fractions that all contain antioxidant activity. However, only one fraction, enriched in proanthocyanidin compounds, increased C. elegans lifespan and thermotolerance (Wilson, et al. Blueberry polyphenols increase lifespan and thermotolerance in Caenorhabditis elegans. Aging Cell. 2006 Feb;5(1):59-68).

A 1999 USDA study showed that a diet rich in blueberry extract reversed some loss of balance and coordination and improved short term memory in aged rats. This was the first study to actually demonstrate a reversal in dysfunctions of behavior, going farther than earlier studies that linked high-antioxidant fruits and vegetables to prevention of function loss only (Journal of Neuroscience, September 15, 1999).

A 2003 Tufts study showed blueberries enhanced memory-associated neuronal signaling and alterations involved in certain neuronal activities and concluded it may be possible to overcome genetic predisposition to Alzheimer’s Disease through diet (Joseph JA et al. Blueberry supplementation enhances signaling and prevents behavioral deficits in an Alzheimer disease model. Nutr Neurosci. J6, 3:153-62, 2003).

Tufts scientists, who have been in the forefront of blueberry research, reported another study in the August 2005 issue of Neurobiology of Aging demonstrating results that suggested that the age-related changes in temporal processing speed in the primary auditory cortex may be reversed by dietary supplementation of blueberry phyto-chemicals (Galli RL, Bielinske DF, Szpringiel A, Shukitt-Hale B, Joseph Ja.  HSP70 neuroprotection. Neurobiol Aging. 2005 Apr. 30). 

A 2005 study to investigate blueberry’s ability to ameliorate age-related deficits in neuronal and behavioral functions, examined whether short-term supplementation with blueberries might enhance the brain’s ability to generate a heat shock protein 70 (HSP70) mediated neuroprotective response to stress. Hippocampal (HC) regions from young and old rats fed either a control or a supplemented diet for 10 weeks were subjected to an in vitro inflammatory challenge (LPS) and then examined for levels of HSP70 at various times post LPS (30, 90, and 240 min). While baseline levels of HSP70 did not differ among the various groups compared to young control diet rats, increases in HSP70 protein levels in response to an in vitro LPS challenge were significantly less in old as compared to young control diet rats at the 30, 90, and 240 min time points. However, it appeared that the blueberry diet completely restored the HSP70 response to LPS in the old rats at the 90 and 240 min times. This suggests that a short-term blueberry intervention may result in improved HSP70-mediated protection against a number of neurodegenerative processes in the brain (Neurobiol Aging. 2005 Apr 30).

Clinical Abstracts

Blueberry polyphenols increase lifespan and thermotolerance in Caenorhabditis elegans

Wilson MA, Shukitt-Hale B, Kalt W, Ingram DK, Joseph JA, Wolkow CA.

Aging Cell. 2006 Feb;5(1):59-68

Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, Baltimore, MD 21224, USA.

The beneficial effects of polyphenol compounds in fruits and vegetables are mainly extrapolated from in vitro studies or short-term dietary supplementation studies. Due to cost and duration, relatively little is known about whether dietary polyphenols are beneficial in whole animals, particularly with respect to aging. To address this question, we examined the effects of blueberry polyphenols on lifespan and aging of the nematode, Caenorhabditis elegans, a useful organism for such a study. We report that a complex mixture of blueberry polyphenols increased lifespan and slowed aging-related declines in C. elegans. We also found that these benefits did not just reflect antioxidant activity in these compounds. For instance, blueberry treatment increased survival during acute heat stress, but was not protective against acute oxidative stress. The blueberry extract consists of three major fractions that all contain antioxidant activity. However, only one fraction, enriched in proanthocyanidin compounds, increased C. elegans lifespan and thermotolerance. To further determine how polyphenols prolonged C. elegans lifespan, we analyzed the genetic requirements for these effects. Prolonged lifespan from this treatment required the presence of a CaMKII pathway that mediates osmotic stress resistance, though not other pathways that affect stress resistance and longevity. In conclusion, polyphenolic compounds in blueberries had robust and reproducible benefits during aging that were separable from antioxidant effects.

PMID: 16441844 [PubMed - indexed for MEDLINE]

Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation.

J Neurosci. 1999 Sep 15;19(18):8114-21 Joseph JA, Shukitt-Hale B, Denisova NA, Bielinski D, Martin A, McEwen JJ, Bickford PC.

United States Department of Agriculture, Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts 02111, USA.

Ample research indicates that age-related neuronal-behavioral decrements are the result of oxidative stress that may be ameliorated by antioxidants. Our previous study had shown that rats given dietary supplements of fruit and vegetable extracts with high antioxidant activity for 8 months beginning at 6 months of age retarded age-related declines in neuronal and cognitive function. The present study showed that such supplements (strawberry, spinach, or blueberry at 14.8, 9.1, or 18.6 gm of dried aqueous extract per kilogram of diet, respectively) fed for 8 weeks to 19-month-old Fischer 344 rats were also effective in reversing age-related deficits in several neuronal and behavioral parameters including: oxotremorine enhancement of K(+)-evoked release of dopamine from striatal slices, carbachol-stimulated GTPase activity, striatal Ca(45) buffering in striatal synaptosomes, motor behavioral performance on the rod walking and accelerod tasks, and Morris water maze performance. These findings suggest that, in addition to their known beneficial effects on cancer and heart disease, phytochemicals present in antioxidant-rich foods may be beneficial in reversing the course of neuronal and behavioral aging.

PMID: 10479711 [PubMed - indexed for MEDLINE]

Blueberry supplementation enhances signaling and prevents behavioral deficits in an Alzheimer disease model.

Nutr Neurosci. 2003 Jun;6(3):153-62

Joseph JA, Denisova NA, Arendash G, Gordon M, Diamond D, Shukitt-Hale B,

Morgan D.

USDA-HNRCA at Tufts University, 711 Washington Street, Boston, MA 02111, USA. james.joseph@tufts.edu

Previously, we showed that blueberry (BB) supplementation reversed the deleterious effects of aging on motor behavior and neuronal signaling in senescent rodents. We now report that BB-fed (from 4 months of age) APP + PS1 transgenic mice showed no deficits in Y-maze performance (at 12 months of age) with no alterations in amyloid beta burden. It appeared that the protective mechanisms are derived from BB-induced enhancement of memory-associated neuronal signaling (e.g. extracellular signal-regulated kinase) and alterations in neutral sphingomyelin-specific phospholipase C activity. Thus, our data indicate for the first time that it may be possible to overcome genetic predispositions to Alzheimer disease through diet.

PMID: 12793519 [PubMed - indexed for MEDLINE]