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      Gastrodin extends the lifespan and protects against neurodegeneration in the Drosophila PINK1 model of Parkinson's disease

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          Abstract

          Gastrodin feeding extends lifespan, improves antioxidant ability, and delays the onset of a Parkinson-like phenotypes in Pink1 B9 mutant, but does not ameliorate the tau-induced neurobehavioral deficits in  Drosophila melanogaster.

          Abstract

          Gastrodin is the main bioactive ingredient of a famous Chinese herb Rhizoma Gastrodiae. Many studies have reported that gastrodin has antioxidative and neuroprotective effects, although its effect on longevity and the mechanism of neuroprotection have not been well studied. Here, we use Drosophila melanogaster as a model to investigate the longevity and neuroprotective effects of gastrodin. Gastrodin significantly extended the lifespan, increased the climbing ability, enhanced the resistance to oxidative stress, increased the enzyme activities of superoxide dismutase (SOD) and catalase (CAT), and promoted the expression of anti-oxidative genes in old flies. The food intake, reproduction and starvation resistance were not affected in flies treated with gastrodin. Moreover, gastrodin delayed the onset of Parkinson-like phenotypes in Pink1 B9 mutant flies, including the prolongation of the lifespan, rescue of the climbing ability, rescue of the progressive loss of a cluster of dopaminergic neurons in the protocerebral posterial lateral 1 region, and increase of the dopamine content in the brain. Gastrodin did not ameliorate the tau-induced neurobehavioral deficits in the fly AD model of taupathy. Together, these results indicate that gastrodin could prolong the lifespan by regulating the antioxidant ability, and protect against neurodegeneration in the Pink1 B9 model of PD. This suggests that gastrodin can be considered as an ideal therapeutic candidate for drug development towards anti-aging.

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          Most cited references39

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          Neural mechanisms of ageing and cognitive decline.

          During the past century, treatments for the diseases of youth and middle age have helped raise life expectancy significantly. However, cognitive decline has emerged as one of the greatest health threats of old age, with nearly 50% of adults over the age of 85 afflicted with Alzheimer's disease. Developing therapeutic interventions for such conditions demands a greater understanding of the processes underlying normal and pathological brain ageing. Recent advances in the biology of ageing in model organisms, together with molecular and systems-level studies of the brain, are beginning to shed light on these mechanisms and their potential roles in cognitive decline.
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            Hereditary early-onset Parkinson's disease caused by mutations in PINK1.

            Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons in the substantia nigra. We previously mapped a locus for a rare familial form of PD to chromosome 1p36 (PARK6). Here we show that mutations in PINK1 (PTEN-induced kinase 1) are associated with PARK6. We have identified two homozygous mutations affecting the PINK1 kinase domain in three consanguineous PARK6 families: a truncating nonsense mutation and a missense mutation at a highly conserved amino acid. Cell culture studies suggest that PINK1 is mitochondrially located and may exert a protective effect on the cell that is abrogated by the mutations, resulting in increased susceptibility to cellular stress. These data provide a direct molecular link between mitochondria and the pathogenesis of PD.
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              Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study.

              Calorie restriction (CR), a reduction of 10–40% in intake of a nutritious diet, is often reported as the most robust non-genetic mechanism to extend lifespan and healthspan. CR is frequently used as a tool to understand mechanisms behind ageing and age-associated diseases. In addition to and independently of increasing lifespan, CR has been reported to delay or prevent the occurrence of many chronic diseases in a variety of animals. Beneficial effects of CR on outcomes such as immune function, motor coordination and resistance to sarcopenia in rhesus monkeys have recently been reported. We report here that a CR regimen implemented in young and older age rhesus monkeys at the National Institute on Aging (NIA) has not improved survival outcomes. Our findings contrast with an ongoing study at the Wisconsin National Primate Research Center (WNPRC), which reported improved survival associated with 30% CR initiated in adult rhesus monkeys (7–14 years) and a preliminary report with a small number of CR monkeys. Over the years, both NIA and WNPRC have extensively documented beneficial health effects of CR in these two apparently parallel studies. The implications of the WNPRC findings were important as they extended CR findings beyond the laboratory rodent and to a long-lived primate. Our study suggests a separation between health effects, morbidity and mortality, and similar to what has been shown in rodents, study design, husbandry and diet composition may strongly affect the life-prolonging effect of CR in a long-lived nonhuman primate.
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                Author and article information

                Contributors
                Journal
                FFOUAI
                Food & Function
                Food Funct.
                Royal Society of Chemistry (RSC)
                2042-6496
                2042-650X
                August 31 2021
                2021
                : 12
                : 17
                : 7816-7824
                Affiliations
                [1 ]Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and The Prevention and Treatment with Traditional Chinese Medicine Research in Gansu Colleges and University, Gansu University of Chinese Medicine, Lanzhou 730000, China
                [2 ]College of Basic Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, China
                [3 ]College of Public Health, Gansu University of Chinese Medicine, Lanzhou 730000, China
                [4 ]Key Laboratory for Transfer of Dunhuang Medicine at the Provincial and Ministerial Level, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China
                [5 ]College of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi'an 710072, China
                Article
                10.1039/D1FO00847A
                41c18a7f-6f9a-471e-8523-0a7d71bc69c2
                © 2021

                http://rsc.li/journals-terms-of-use

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