La calorie restriction (RC) has been at the centre of interest for decades among many scientists involved in studies on silent chronic inflammation and especially on aging. In this regard, the neologism was also coined, inflammaging, term that derives from the fusion of inflammation (inflammation) and aging (aging).
It was demonstrated that a reduced caloric intake (20-40% less in the diet daily), without malnutrition, protects against aging and related diseases. This protective effect leads to a reduction in inflammatory processes, an improvement in the immune system (thymic function) (1) and epigenetic methylation of DNA (2).
Il trial clinical CALORIE (Comprehensive Assessment of Long-term Effects of Reducing Energy Intake), designed to study the effects of CR on healthy volunteers, has demonstrated that a 25% reduction in calories, without a specific diet, shifts the immunometabolic status in a direction that protects human health (3, 4).
Restricting food intake causes cells to enter a protection mode, allowing cells on a diet to meet their needs through a self-cannibalism, scientifically defined autophagy, of aged and poorly functional components. In practice, therefore, the RC activates a sort of "cleaning intern” which removes the deteriorated, potentially dangerous components, stimulating the cell regeneration.
At the same time, the broad and increasingly recognized beneficial properties of plant phenolic compounds, have led to them being proposed as nutraceuticals and, the foods that contain them, such as Functional foods.
Some clinical research, epidemiological and observational studies have reported an association between the physio-metabolic effects of biophenols, the Mediterranean Diet (e.g. resveratrol from red wine, hydroxytyrosol and oleuropein from olive oil, consumed in Italy, Spain, Greece) and the Asian diet (e.g. in Japan, with the isoflavones from soy and epigallocatechin gallate from green tea) being similar to RC in humans, indicating these substances are “RC imitators” (5)
Interestingly, compared to CR, biophenols activate similar molecular targets such as sirtuin (Sirt, is a α-dependent deacetylase). nicotinamide adenine dinucleotide redox coenzyme or NAD) suggesting that a so-called “MediterraneanAsian“, which combines foods that activate sirtuin (sirtfood) of the Asian and Mediterranean diet, may represent a promising dietary strategy to prevent chronic diseases, thus ensuring health and healthy aging (6, 7).
Dietary composition influences health, therefore it has been hypothesized that CR and some dietary factors may prevent age-related diseases such as atherosclerosis, cardiovascular diseases, type 2 diabetes mellitus, neurodegenerative diseases and cancer.
Interestingly, biophenol consumption and CR have similar effects on metabolism in humans, and polyphenol supplementation attenuates, in experimental animals, the negative effects of a high-fat diet. For this, Biophenols are also referred to as “CR mimetics”.
An important mechanism through which Polyphenols induce CR-like signaling pathways It appears to work through the activation of sirtuin, in reference to foods such as olive oil, soy, red wine, the so-called “sirt foods”; (also: green cabbage, strawberries, chili pepper, chocolate, coffee, matcha green tea, walnuts, red onion, parsley, arugula, red chicory, turmeric, buckwheat, capers…)
However, CR can hardly be sustained for long periods of time; therefore, dietary supplementation with factors capable of imitate the beneficial effects of a reduction in caloric intake, can be very much appreciated. Biophenols, including those from olives, induce CR-like effects in muscle, brain, adipose tissue, and kidney in several ways, particularly through activation and increased levels of sirtuins (8. 9).
Many of the cellular effects of Sirt are mediated by gene regulation as a result of its ability to epigenically control acetylation/deacetylation status DNA, and therefore the activity, of different transcription factors, including p53, FOXO, NFκB, Nrf2, PPARα/γ, PGC1α, and LXR.
I remember that these factors are involved in the control of apoptosis (programmed cell death), of theautophagy (mechanism for eliminating non-functioning components), of the cell proliferation, the oxidative stress, of inflammation and protein synthesis, from the metabolism of the carbohydrates and lipids.
Sirt induction by RC or biophenols results in some cellular changes considered responsible for epigenetic effectsi, in particular:
- contrasts inflammation, lowers the synthesis of cholesterol and triglycerides;
- reduces it oxidative stress and markers of oxidative damage by increasing the expression of transcription factor-dependent genes nrf2 (Nuclear Factor Erythroid 2-related factor 2) That modulates antioxidant factors;
- reduces the pro-inflammatory transcription factor NFκB (Nuclear Factor kappa-light-chain-enhancer of activated B cells) inhibiting the inflammatory response;
- inhibits the transcriptional activity of PPARγ (Peroxisome Proliferator-Activated Receptor Gamma), with consequent anti-adipogenic effects.
It has been demonstrated that biophenols in EVO oil, in particular Oleuropein, directly modulate the insulin/IGF1/AKT and mTOR pathways, whose inhibition results in the activation of the transcription factor FOXO3 (Forkhead box O3) with consequent transcription of homeostatic genes that promote longevity and reduce inflammatory conditions.
Aging depends on the “ratio” between two “molecular bioregulators” mTORC / AMPK; (mTORC, mammalian Target Of Rapamycin Complex and the AMPK enzyme: Adenosine Monophosphate-activated Protein Kinase).
The mTORC (or gerogene) is the enzyme (protein kinase) that regulates cell growth; AMPK (or gerosine suppressor) is the enzyme that regulates the energy balance activated by fasting and from physical activity.
Oleuropein has a suppressive action on mTORC, with the same mechanism as rapamycin, a molecule extracted from soil bacteria on Easter Island (Rapa Nui), capable of slowing down cellular aging.
AMPK predominates over mTOR at kilometer 30 of a marathon, or after fasting, while mTORC predominates over AMPK after a nutrient-rich post-workout meal (10). In practice, the mTORC complex is responsible for growth and inhibits autophagy, which is the reverse operation.
Overall, the currently available data support the idea that several plant biophenols, including those from olive (oil and leaves), are able to mimic the effects of CR by acting on the same (multiple) cellular targets and that they can be considered for the long-term prevention and/or treatment of age-related diseases resulting from chronic inflammation, transcriptional disorders, redox or metabolic.
Bibliography
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- Waziry R. et al. Nature Aging. 2023; 3, 248–57.
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- Vujovic A. Olive Oil between History and Science. 2020, Ed. Tozzuolo Perugia; chapter 17.28, pp. 431-35.
