title: Effects of Grape Skin Extract on Age-Related Mitochondrial Dysfunction, Memory and Life Span in C57BL/6J Mice.
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.
authors.affiliation: Department of Pharmacology, Biocenter Campus Riedberg, Goethe-University of Frankfurt, 60438, Frankfurt, Germany.|Institute of Nutritional Sciences, University of Giessen, Wilhelmstraße 20, 35392, Giessen, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Asseburg
authors.affiliation: Department of Pharmacology, Biocenter Campus Riedberg, Goethe-University of Frankfurt, 60438, Frankfurt, Germany.
authors.forename: Carmina
authors.initials: C
authors.lastname: Schäfer
authors.affiliation: Provadis School of International Management and Technology AG, 65929, Frankfurt, Germany.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Müller
authors.affiliation: Department of Pharmacology, Biocenter Campus Riedberg, Goethe-University of Frankfurt, 60438, Frankfurt, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hagl
authors.affiliation: Department of Pharmacology, Biocenter Campus Riedberg, Goethe-University of Frankfurt, 60438, Frankfurt, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Pohland
authors.affiliation: Department of Pharmacology, Biocenter Campus Riedberg, Goethe-University of Frankfurt, 60438, Frankfurt, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Berressem
authors.affiliation: Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Borchiellini
authors.affiliation: Department of Pharmacology, Biocenter Campus Riedberg, Goethe-University of Frankfurt, 60438, Frankfurt, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Plank
authors.affiliation: Department of Pharmacology, Biocenter Campus Riedberg, Goethe-University of Frankfurt, 60438, Frankfurt, Germany. Gunter.Eckert@ernaehrung.uni-giessen.de.|Institute of Nutritional Sciences, University of Giessen, Wilhelmstraße 20, 35392, Giessen, Germany. Gunter.Eckert@ernaehrung.uni-giessen.de.
authors.forename: Gunter P
authors.initials: GP
authors.lastname: Eckert
mesh_terms: D000375:Aging; D000818:Animals; D001921:Brain / Q000473:pathology; D008136:Longevity / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D010936:Plant Extracts / Q000494:pharmacology*; D027843:Vitis / Q000737:chemistry*
chemical_list: D010936:Plant Extracts
keywords: Brain aging; Grape polyphenols; Hormesis; Life span; Memory; Mitochondria