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Neuromolecular Med. 2016 Sep;18(3):378-95. doi: 10.1007/s12017-016-8428-4. Epub 2016 Jul 25.

Effects of Grape Skin Extract on Age-Related Mitochondrial Dysfunction, Memory and Life Span in C57BL/6J Mice.

Author information

1
Department of Pharmacology, Biocenter Campus Riedberg, Goethe-University of Frankfurt, 60438, Frankfurt, Germany.
2
Institute of Nutritional Sciences, University of Giessen, Wilhelmstraße 20, 35392, Giessen, Germany.
3
Provadis School of International Management and Technology AG, 65929, Frankfurt, Germany.
4
Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy.
5
Department of Pharmacology, Biocenter Campus Riedberg, Goethe-University of Frankfurt, 60438, Frankfurt, Germany. Gunter.Eckert@ernaehrung.uni-giessen.de.
6
Institute of Nutritional Sciences, University of Giessen, Wilhelmstraße 20, 35392, Giessen, Germany. Gunter.Eckert@ernaehrung.uni-giessen.de.

Abstract

Dementia contributes substantially to the burden of disability experienced at old age, and mitochondrial dysfunction (MD) was identified as common final pathway in brain aging and Alzheimer's disease. Due to its early appearance, MD is a promising target for nutritional prevention strategies and polyphenols as potential neurohormetic inducers may be strong neuroprotective candidates. This study aimed to investigate the effects of a polyphenol-rich grape skin extract (PGE) on age-related dysfunctions of brain mitochondria, memory, life span and potential hormetic pathways in C57BL/6J mice. PGE was administered at a dose of 200 mg/kg body weight/d in a 3-week short-term, 6-month long-term and life-long study. MD in the brains of aged mice (19-22 months old) compared to young mice (3 months old) was demonstrated by lower ATP levels and by impaired mitochondrial respiratory complex activity (except for mice treated with antioxidant-depleted food pellets). Long-term PGE feeding partly enhanced brain mitochondrial respiration with only minor beneficial effect on brain ATP levels and memory of aged mice. Life-long PGE feeding led to a transient but significant shift of survival curve toward higher survival rates but without effect on the overall survival. The moderate effects of PGE were associated with elevated SIRT1 but not SIRT3 mRNA expressions in brain and liver tissue. The beneficial effects of the grape extract may have been influenced by the profile of bioavailable polyphenols and the starting point of interventions.

KEYWORDS:

Brain aging; Grape polyphenols; Hormesis; Life span; Memory; Mitochondria

PMID:
27455862
DOI:
10.1007/s12017-016-8428-4
[Indexed for MEDLINE]

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