Abstract
Numerous studies highlighted the beneficial effects of the Mediterranean diet (MD) in maintaining health, especially during ageing. Even neurodegeneration, which is part of the natural ageing process, as well as the foundation of ageing-related neurodegenerative disorders like Alzheimer’s and Parkinson’s disease (PD), was successfully targeted by MD. In this regard, olive oil and its polyphenolic constituents have received increasing attention in the last years. Thus, this study focuses on two main olive oil polyphenols, hydroxytyrosol (HT) and oleuropein aglycone (OLE), and their effects on ageing symptoms with special attention to PD. In order to avoid long-lasting, expensive, and ethically controversial experiments, the established invertebrate model organism Caenorhabditis elegans was used to test HT and OLE treatments. Interestingly, both polyphenols were able to increase the survival after heat stress, but only HT could prolong the lifespan in unstressed conditions. Furthermore, in aged worms, HT and OLE caused improvements of locomotive behavior and the attenuation of autofluorescence as a marker for ageing. In addition, by using three different C. elegans PD models, HT and OLE were shown i) to enhance locomotion in worms suffering from α-synuclein-expression in muscles or rotenone exposure, ii) to reduce α-synuclein accumulation in muscles cells, and iii) to prevent neurodegeneration in α-synuclein-containing dopaminergic neurons. Hormesis, antioxidative capacities and an activity-boost of the proteasome & phase II detoxifying enzymes are discussed as potential underlying causes for these beneficial effects. Further biological and medical trials are indicated to assess the full potential of HT and OLE and to uncover their mode of action.
Highlights
Neurodegenerative diseases are becoming increasingly prevalent in the ageing populations of industrialized nations, going hand in hand with the increase in life expectancy
Parkinson’s disease (PD) is a chronic, age-related and adult-onset neurodegenerative disorder characterized by the loss of dopaminergic neurons in an area of the midbrain called substantia nigra (SN) along with intraneuronal inclusions known as Lewy bodies, which contain amyloid aggregates of misfolded α-synuclein [2,3,4]
oleurop4 eofin23 aglycone (OLE) treatment did not result in any significant lifespan enhancement (Figure 3A): The mean lifespan of wild type nematodes was only hardly noticeably increased by 2.7%, which is probably the result of a minor, not significant, increase in the median lifespan from 22.55 days to 23.31 days (Table 1)
Summary
Neurodegenerative diseases are becoming increasingly prevalent in the ageing populations of industrialized nations, going hand in hand with the increase in life expectancy. OLE treatment resulted in a remarkable increase of the number of thrashes per minute (Figure 5A) and of the activity index (Figure 5C) displayed by worms at all three tested stages, whereas the body wave number was decreased at the 7th and 12th day of adulthood (Figure 5B). OLE treatment increased the activity index in young nematodes (Figure 8C) but resulted only in minor and non-significant changes of the thrashing rate and body wave. The potential polyphenolic inhibition of the pathological α-synuclein accumulation in muscles can be observed via fluorescence microscopy Treatment of this model with either polyphenol resulted in a progressive reduction of α-synuclein accumulation in the body wall muscle cells compared to the control groups: The reduction of α-synuclein accumulation was about 5% at day 3 and 8% at day 7 and 12 of adulthood in OLE-treated groups (Figure 9). This could be an alternative explanation for the missing life-prolonging effects in the OLE-treated group
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