A reduced calorie amount in the daily diet (or calorie restriction, CR), without incurring malnutrition or lack of essential nutrients, it promotes both longevity that a aging healthy and, in this process, theautophagy plays a vital role.
What is autophagy? It is the process by which the cells of our organism feed on proteins and other unused material, coming from the destruction of senescent cells, practically their recycling, thus becoming a means that on the one hand allows the supply of energy for the cell and on the other promotes the elimination of waste or defective, potentially harmful molecules.
Autophagy is never a destructive process for its own sake, it always is a destroy to reuse; in short, the cells use criteria of “ecology and sustainability" (Christian De Duve, Nobel Prize winner in 1974 and Yoshinori Ohsumi, Nobel Prize winner for autophagy, 2016).
However, autophagy, which in the aging process would need to be more functional, instead - in this period - decreases its effectiveness leading to the development of a series of diseases such as neurodegenerative diseases, diabetes, cancer and immune system disorders.
In fact, it has been seen that this mechanism is defective in some diseases, calledproteopathies“, such as Alzheimer's and Parkinson's, where the accumulation of misfolded proteins (amyloid/tau and alpha-synuclein), residues of poorly made proteins and, with neurons lacking an effective system for their recycling, these cells suffer and die.
Autophagy allows you to create and destroy at precise times, marks a “molecular clock” with which the cell dictates the rhythm of its own division cycle and, without this degradation, the cell would undergo uncontrolled proliferation and even the formation of tumors.
The biological mechanisms of calorie restriction include: the stimulation of autophagy, modification of energy metabolism, reduction of oxidative stress, suppression of chronic inflammation and induction ofhormesis (this is an adaptive function with a dose/response reaction characterized by a biphasic effect, at low doses stimulant and at high doses inhibitory – Arndt Schultz law. On the merits already in 1500 Paracelsus wrote «Omnia venenum sunt: nec sine veneno quicquam existit. Dosis sola facit, ut venenum non fit.»).
I natural polyphenols, present in foods, as well as the ability to induce autophagy, stimulate the processes of hormesis and are able to modulate the expression of factors linked to apoptosis, of neutralize free radicals, to influence mitochondrial functions, of chelate the ions of “transition metals” and to prevent protein aggregation, the latter cause of proteopathies.
Polyphenols, present in many parts of higher plants, as secondary metabolites - even if in small quantities, according to the principle of hormesis -, modulate apoptosis, they induce autophagy, improve the mitochondrial function, they have a business antioxidant e anti-radical, inflammatory ed antitumor, antiviral e antibacterial, also carrying out a neuro-cardio-protection.
In this way they lead to an increase in life expectancy.
I plant polyphenols, among them theepigallocatechin gallate (green tea), the resveratrol (grapes, wine, blackberries, cocoa), quercetin (capers, onion, celery), curcumin (Curcuma longa), apigenin (celery), gingerol (ginger), fisetin (onions, cucumbers), including those of the olive tree and oil, (hydroxytyrosol and oleuropein), induce similar effects to calorie restriction in muscles, brain, adipose tissue and kidneys through the activation and increase in levels of deacetylating enzymes, such as sirtuins (Sirt), whose activity depends on NAD +, as a cofactor (NAD +, acronym for Nicotinamide Adenine Dinucleotide, oxidoreductive coenzyme in its oxidized form). Indeed we can say that a new concept of food has emerged, the "sirtfood“, which modulates SIRT (1–7) genes capable of influencing health (Otobong Donald Akan 2022).
Sirtuins control gene expression and, in addition to the regulation ofautophagy, determine a better functionality, on the part of the polyphenols, of themitochondrial activity and modulatoryapoptosis (or programmed cell death).
So the molecules that mimic the effect of calorie restriction, without reducing food intake, are known as “molecules camouflages of caloric restriction" and the substances known so far are phenolic compounds, rapamycin, 2-deoxy-D-glucose and other glycolytic inhibitors, which act on the same signaling pathways as CR.
There are numerous studies that indicate that i polyphenols I am able to modify, through the modulation of epigenetic mechanisms, the regulation of the activities of DNA-methyltransferase (enzyme that methylates genes, silencing them) and deacetylases (enzymes that deacetylate genes, making them expressive).
I remember that DNA is wrapped around histones, its expression is regulated by methylation/demethylation, acetylation/deacetylation and also other mechanisms, which act by compacting or despiralizing the DNA.
There is also growing evidence that epigenetic processes, among other things reversible, are modulated by dietary components, in particular by polyphenols which induce the deacetylation of more than a dozen cytoplasmic proteins and SIRT1 also deacetylates the transcription factors p53, NF-kB, HSF1, FOXO1, 3, 4 and PGC1a, for which the effects on the control of lifespan are known.
It is known that these factors are involved in the control of apoptosis, autophagy, cell proliferation, oxidative stress, inflammation, protein synthesis, glucose and lipid metabolism.
The consumption of phenolic compounds or calorie restriction I'm the only intervention, not genetic, which extends the lifespan of organisms, delaying or reducing the risk of many age-related diseases.
Overall, the currently available data support the idea that several plant polyphenols, including those of olive leaf and oil, are able to imitate the effects of caloric restriction, influencing some cellular targets (activation of SIRT1 and AMPK gerosuppressor and the inhibition of gerontogenic mTORC) and therefore can be considered for the prevention and/or treatment of aging-associated diseases resulting from chronic or transcriptional inflammation, redox alterations or metabolic imbalance.
Blanco-Benitez M. et al. 2022 Molecular Cellular Oncology; 9, 1. e2044263 https://doi.org/10.1080/23723556.2022.2044263
Isis C, et al. 2020 Front. Pharmacol. Sec. Translational Pharmacology. 11, https://doi.org/10.3389/fphar.2020.01225
Musial C. et al. 2021 Antioxidants.16;10(1):123. https://www.mdpi.com/2076-3921/10/1/123
Hidalgo-Moyano C. et al. 2022 Nutrients. 14(18): 3789. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9504765/
Li X. et al. 2021, Front. Cell Dev. Biol. 2; 9: 641315. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039379/
Donald Akan O. et al. 2022 Foods, 11 (19), 2955; https://www.mdpi.com/2304-8158/11/19/2955
Vujovic A. Olive oil between history and science. 2020, Tozzuolo Editore Perugia. Ch 17.27; pages 429-435.
