Hi Everyone! Welcome back to another Friday blog. Today I wanted to look at AUTOPHAGY. What IS autophagy, and how do we make it happen?

Autophagy: (auto “self” phage “eat”) This is a clean up and recycle process the body does to take care of misfolded or mutant proteins, bacteria, viruses and other molecules in order to maintain cellular homeostasis. It declines with age, contributing to a build up of harmful protein aggregates, damaged mitochondria (powers the cell) and reactive oxygen species (ROS). Our bodies literally will take the ‘trash’ and recycle it to make antioxidants and new proteins and enzymes to aid in correcting all the mistakes and damage. It can be up-regulated in response to several stimuli, such as “hypoxia, nutritional deprivation, DNA damage, and cytotoxic agents.” It stimulates proteostasis. Proteostasis is a network of competing and integrated biological pathways that control biogenesis, folding, trafficking and degradation of proteins inside and outside the cell. 

“Proteostasis is central to understanding the cause of diseases associated with excessive protein misfolding and degradation leading to loss-of-function phenotypes,^[3] as well as aggregation-associated degenerative disorders.^[4] Therapeutic restoration of proteostasis may treat or resolve these pathologies.^[5] Cellular proteostasis is key to ensuring successful development, healthy aging, resistance to environmental stresses, and to minimize homeostatic perturbations from pathogens such as viruses.” 

Okay. Why is this important? Autophagy is the “re-set” button for our bodies. This process is one of the most IMPORTANT in preventing disease and prolonging life. Aging is “considered a risk factor for several diseases such as cancer, neurodegenerative diseases, cardiovascular diseases, and diabetes, most of which have an oxidative and inflammatory base.”

The molecular mechanisms of autophagy were first elucidated in the 1990s by Yoshinori Ohsumi for which he was awarded the 2016 Nobel Prize in Physiology or Medicine. Unfortunately, as we age, this process is not as efficient. This results in a build-up of these damaged, non-functioning materials in the body. What do you think all this debris just sitting around trashing up the joint does to our tissue? It causes INFLAMMATION!!! Inflammation is at the root of ALL disease processes. The accumulation of dysfunctional mitochondria (energy producer of the cell) has been linked to a variety of ageing-related diseases. We know that the accumulation of amyloid and tau proteins in the brain is linked to Alzheimer’s Disease and Dementia. It only makes sense that accumulation of malfunctioning materials in other organs and blood vessels result in other diseases, such as autoimmune disorders, cardiovascular disease, non-alcoholic fatty liver, diabetes or metabolic syndrome…

Okay, so how do we stimulate autophagy? One of the best ways is through Intermittent Fasting (IF). In fact, it takes about 16 hours without food intake just to initiate it. The longer time you can go before eating your next meal (up to around 72 hours), the better the results. When looking at mice, researchers determined that a 1:3 ratio is OPTIMAL for longevity. Current studies looking at 2:5 ratio are being investigated. Published in the Journal of Nutrition:

Just by doing this, it increased the lifespan in males by 20% and females by 15%!! That’s HUGE. Further, it slowed the development of mammary tumors!! So, what’s happening? “In humans, intermittent fasting improves weight, insulin resistance, inflammation, dyslipidemia, and hypertension.[1] IF has also reduced tumor growth, boosted stem cell production, and increased lifespan in mice.[2] One compelling explanation for these outcomes relates to a term called adaptive stress—a type of physiological stress that elicits positive responses. During fasting, cells undergo adaptive stress, which activates different pathways in the body, resulting in a range of effects, including increased production of antioxidants, DNA repair, autophagy (the removal of damaged or dead cells), and decreased inflammation.” 

Okay, so we can stimulate autophagy through IF. What about food sources that stimulate autophagy? Guess what? EVOO stimulates autophagy!! The polyphenols and anti-oxidants in high polyphenol EVOO are amazing at stimulating this phenomenon. “Polyphenols are mostly antioxidant and anti-inflammatory compounds, able to modulate abnormal cellular signaling induced by pro-inflammatory stimuli and oxidative stress, as that related to NF-E2-related factor 2 (Nrf-2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), which have been identified as important modulators of age-related disorders and aging itself.” Hydroxytyrosol is just one of the amazing polyphenols in EVOO that has been shown to enhance autophagy. It is able to activate regulatory pathways to induce autophagy in response to damage from H2O2 and other inflammatory molecules. 

In a study released in July, 2021 in the International Journal of Molecular Science, researchers looked at the combination of 2 polyphenols rich in EVOO, hydroxytyrosol and Oleuropein on damaged neurons as in Alzheimer’s Disease. “Our data show that the mixture of the two polyphenols activates synergistically the autophagic flux preventing cell damage by Aβ_1–42oligomers., in terms of ROS production, and impairment of mitochondria.” They go further to say that “EVOO polyphenols act synergistically in autophagy modulation against neurodegeneration.”

Researchers looking at Oleuropein report a wide range of diverse healing properties. In the blood vessels, it has anti-platelet aggregation, vasodilation, hypotensive, anti-rheumatic, antipyretic and diuretic effects. It exerts its ability to prevent free radicals by chelating metal ions, such as Cu and Fe that catalyze free radical generation, therefore preventing oxidation of LDLs (low-density lipoproteins). It inhibits oxidative stress and hyperglycemia (diabetes II). Polyphenols in EVOO prevent the formation as well as kill cancer cells throughout the body as well as skin cells chronically exposed to UBV rays. Researchers state, “a plethora of minor constituents in olive oil have been identified as effective agents in mitigating the initiation, promotion and progression of multistage carcinogenesis.”

Not only does EVOO protect and prevent multiple chronic non-communicable disease processes, but it exerts antimicrobial properties. “Oleuropein has been shown to have strong antimicrobial activity against both Gram-negative and Gram-positive bacteria [57–59] as well as mycoplasma.” It has been demonstrated that this polyphenol disrupts the cell membrane and cell proteoglycans, as well as impeding the formation of bacterial proteins necessary for bacterial survival. It is “able to inhibit the development and production of enterotoxin B by Staphylococcus aureus, the development of Salmonella enteritidis and the germination and consequent development of spores of Bacillus cereus [57–67]. Oleuropein and other phenolic compounds (p-hydroxybenzoic, vanillic and p-coumaric acids) completely inhibit the development of Klebsiella pneumoniae, Escherichia coli and B. cereus [58]. Recently, Sudjana et al. [68] showed the antimicrobial activity of commercial Olea europaea (olive) leaf extracts (abundantly oleuropein) against Campylobacter jejuni, Helicobacter pylori and methicillin-resistant Staphylococcus aureus (MRSA). The authors also demonstrated these extracts play a role in regulating the composition of the gastric flora by selectively reducing levels of H. pylori and C. jejuni.” WHAT?!!!

Furthermore, EVOO exerts antiviral effects on multiple viruses in vitro. It has been demonstrated that Oleuropein exhibits a significant antiviral activity against respiratory syncytial virus and para-influenza type 3 virus, as well as inhibiting HIV cell to cell infection. “Cell-to-cell transmission of HIV was inhibited in a dose-dependent manner with EC₅₀s of 0.2 μg/ml, and HIV replication was inhibited in an in vitro experiment [73]. In a U.S. patent, it has been claimed that oleuropein has potent antiviral activities against herpes mononucleosis, hepatitis virus, rotavirus, bovine rhinovirus, canine parvovirus, and feline leukemia virus [69].”

The anti-aging effects of EVOO polyphenols are outstanding. Human fibroblasts undergo replicative senescence (gradual deterioration of function due to aging) due to genetic and environmental factors. “The proteasome, a multicatalytic nonlysosomal protease, has impaired function during aging, while its increased expression delays senescence in human fibroblasts.” Oleuropein enhances proteasome activities in vitro more effectively than other known chemical activators, possibly through conformational changes of the proteasome.” This is awesome!!!  Researchers continuously treated human embryonic fibroblasts with oleuropein which reduced the ROS, amount of oxidized proteins, increased proteasome-mediated degradation and protected the proteasome function during replicative senescence. They reported that “oleuropein-treated cultures exhibit a delay in the appearance of senescence morphology, and their life span is extended by approximately 15% [77].” WHAT???!!! The cell’s life span was extended 15%?? That’s in line with what IF does, right?

Okay, so we know we can stimulate autophagy through IF and EVOO. Interestingly, there are other compounds high in polyphenols that also go a long way to contribute to healthy aging and longevity. Turmeric, ashwagandha and other Ayurvedic herbs that activate the AMPK pathway stimulate autophagy. “Curcumin, a major bioactive compound in turmeric, has a broad spectrum of activity, including antioxidant, anticarcinogenic, and anti-inflammatory properties.” Researchers were able to confirm that curcumin inhibits cancer cell growth by activating apoptosis (cell death) and enhances cross-talk between apoptosis and autophagy! If you decide to take oral turmeric, make sure it also contains black pepper to increase absorption by more than 70%. Eat foods high in zinc. Zinc is a cofactor for >300 enzymes and is bound to 10% of all proteins. 

Let’s recap. Autophagy prolongs life and prevents disease. You can stimulate autophagy through intermittent fasting, EVOO and turmeric. IF can be difficult to do in our 3-meal-a-day society. However, it could be easier than you think. Let’s say you take your EVOO shot in the morning and have your coffee. You will be satisfied for a long time. If you drink lemon-water or just water, take your supplements before bed, maybe an herbal tea and sleep! You can get 24 hours of fasting without much of a try. Just doing this a couple days/week can go a long way in healing your body, preventing disease and prolonging life. 

So, until next time my friends, boost your health and your immune system!!! Drink, drizzle, digest high polyphenol EVOO, eat fatty fish rich in Omega 3s, eat focus on functional foods, drink lots of water, take a good pre/probiotic to balance your gut microbiome, exercise your body and mind, work in IF a couple days a week, get plenty of sleep…and turn off the light!  Stay healthy my friends #EVOO