Autophagy is a cellular process that repairs and cleans up your cells resulting in increased longevity, lowered neurodegenerative diseases and less chronic illness; fasting, exercise and certain natural compounds can promote autophagy.
Housekeeping for cells
Autophagy is a natural cellular process meaning "self-eating," where cells undergo a controlled degradation of poorly performing or even non-performing components, preventing them from damaging the whole cell, and thus your whole body. Autophagy also reassembles important components from recycled parts. Result - a perfectly performing cell. New for Old.
Perhaps the best way of describing it as a natural form of housekeeping where the cell tidies itself up. The cells get rid of the unnecessary clutter like folded proteins or proteins that have stuck together. This protects the cell from damage. It is essentially a survival system in times of forced fasting, stress, or hypoxia (low oxygen). It's not always plain sailing - some compounds such as acetyltransferases block autophagy.
Most usually though, it means that your cells are in the best condition they can be.
Not surprisingly, autophagy is linked to low chronic illness rates, low neurodegenerative disease levels and increased longevity.
Let me give you an example. Throughout America there are power stations. Many work perfectly, some are getting old and produce less energy, others are at the end of their lives and need to be shut down.
Your cell is no different - it contains up to a thousand power stations. These are your mitochondria - they are so small they are called organelles; tiny organs. Some work perfectly, others less so, and some are at the end of the road. Autophagy is a controlled process, where all the poor or non-performers are broken down and their contents are often recycled to build new power stations. Result? After the process, 100% of your mitochondria work perfectly. Why is that so good? Well you now make your energy in the cell efficiently and you have no mitochondria that are firing off random electrons which could potentially damage the whole cell. People with high levels of perfectly working mitochondria exhibit longer lives and less chronic illness.
What promotes autophagy?
Fasting - Intermittent Fasting for several days, rather than Time Restricted Fasting, is linked to these cellular clean up systems and autophagy (1). While some effects start around the 36 hour mark, significant autophagy requires 2 to 4 days of fasting according to the few studies to date. But 24 hour fasts can trigger autophagy when combined with exercise.
Exercise - 2012 research (2) from the Center of Autophagy Research in Texas Medical School, showed that exercise could promote autophagy in metabolic organs such as muscle, heart, liver and even your brain. It is well known that performance athletes build higher levels of high performance mitochondria in their cells. But for these studies they put mice on a training programme for 8 weeks (Yes, really!). At the end, the mice were stronger and had better endurance.
What Natural Compounds help promote autophagy?
By and large, the natural compounds that help most, are the ones that mimic fasting by targeting key pathways in the cell such as mTOR, AMPK, PI3K/AKT, and SIRT, thus promoting cellular renewal and resilience.
Here are 10 foods and compounds you should be focusing on: -
i) Mushrooms contain a polyamine called spermidine which inhibits acetyltransferases, thus enhancing cellular cleanup and supporting longevity. Studies show spermadine can extend your lifespan and improve cognitive and heart health.
ii) Resveratrol. present in red grapes, pomegranate and cranberries, and red wine, activates SIRT1 and AMPK, key regulators of energy metabolism and autophagy, providing neuroprotective and mitochondrial health benefits.
iii) Curcumin (from Turmeric) enhances autophagy by upregulating Beclin-1 and LC3-II/I, while modulating the AKT/mTOR pathway, and is noted for its ability to cross the blood-brain barrier.
iv) Vitamin D plays a critical role in regulating autophagy; it activates autophagy through both genomic (via the Vitamin D Receptor, VDR) and non-genomic signaling pathways. Vitamin D down regulates mTOR, a key inhibitor of autophagy.
v) Fisetin, found in strawberries, onions, apples, mangoes and cucumbers activates autophagy via p8-dependent pathways and AMPK, supporting cognitive function and cellular renewal.
vi) Berberine, from oregon grape, goldenseal, berberis and other plants used in traditional medicine, induces autophagy through AMPK and SIRT1 activation, with potential benefits for metabolic and neurodegenerative diseases.
vii) Berries, particularly blackberries, raspberries, and strawberries, are rich sources of ellagic acid (EA), a polyphenolic compound known for its anti-inflammatory and antioxidant properties. Walnuts also contain high levels. Research highlights that ellagic acid can activate autophagy and apoptosis to combat cancer cells and protect healthy tissues.
viii) Chlorogenic acid (CGA) derived from ellagic acid in the gut is also phenolic compound that acts as a potent modulator of autophagy typically enhancing it to protect against cell injury, oxidative stress, and neurodegeneration via the AMPK/mTOR/TFEB signaling pathway. It reduces amyloid damage in neurons, improves liver function and increases longevity. Less than 20% of people have this compound in their bodies.
ix) Genistein is a natural isoflavone found in soy that has been shown to induce autophagy; Its effects are particularly significant in neurodegenerative diseases. It inhibits mTOR and crosses the blood brain barrier.
x) Omega-3 fatty acids (DHA/EPA) from sea fish, and lutein also show autophagy-modulating effects, particularly in protecting cells from oxidative stress and supporting brain and liver function.
Some natural compounds promote both autophagy and apoptosis.
For example, the number 1 Ayurvedic herb Tulsi, or Holy Basil, is known to do both. Holy basil is recognised for protecting cells from damage (autophagy), particularly in the liver, heart, and brain. Its phytochemicals, such as eugenol and ursolic acid, help prevent cellular damage and support detoxification.
It also helps with the removal of severely damaged or abnormal cells by promoting apoptosis (programmed cell death) and inhibiting tumor growth.
Go to: What is apoptosis?
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References
1. The Beneficial and Adverse Effects of Autophagic Response to Caloric Restriction and Fasting; Roya Shabkhisan et al; Adv Nutr. 2023 Jul 30;14(5):1211–1225.
2. Exercise induces autophagy in peripheral tissues and in the brain; Congcong He et al; Autophagy. 2012 Oct 1;8(10):1548–1551.