Our experts continually monitor the health and wellness space, and we update our articles when new information becomes available. Fasting, or not eating food for an extended period of time, is well-known as a religious diet practice.

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Autophagy: What You Need to Know. Medically reviewed by Daniel Murrell, M. Benefits Dietary changes Bottom line Autophagy is a natural, self-preservation mechanism whereby the body removes damaged or dysfunctional parts of a cell and recycles other parts toward cellular repair.

The researchers were also able to identify how the brain communicates with the liver. When energy levels are low, the nerve cells trigger the release of the hormone corticosterone, which then stimulates the activation of autophagy in the liver cells.

They were also able to clarify in detail the exact pathways that the signal travels in the brain and thus determine which nerve cells are involved in the process.

They were also able to show that blocking this signal transmission leads to autophagy not kicking in despite fasting. The researchers assume that the brain gives the first initial signal to initiate autophagy quickly.

They think that the cells in the liver would also start the recycling system themselves, but only at a later stage. In the long term, we would like to find out whether this newly discovered mechanism in the brain contributes to the positive effects of fasting," explains Jens Brüning, head of the study and director at the Max Planck Institute for Metabolism Research.

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Homepage Newsroom From the Institutes Brain tells liver to start recycling after fasting. Brain tells liver to start recycling after fasting The brain releases the hormone corticosterone after short fasting that boosts autophagy.

A handful of human studies also show extended fasts lead to increased autophagic activity through various mechanisms. Exercise also induces autophagy in muscle tissue[]. Autophagy markers immediately increase after short bouts of intense exercise and also over the course of longer moderate-intensity training sessions.

However, one study found that exercise intensity was more powerful at inducing autophagy, independent of whether fasting was involved [9]. The current evidence suggests that anywhere between 18 hours as evidenced by the eTFR study to four days will trigger autophagy.

Interestingly, protein-based beverages may decrease autophagy activity. the non-fasting periods. A decrease in autophagy occurred when the men sipped on the protein-rich beverages leucine-rich whey or soy-based protein but not the carbohydrate-rich ones.

The researchers noted that these findings align with rodent studies where branched-chain amino acids tend to suppress autophagy during catabolic conditions like fasting.

Glucose, on the other hand, does not impact autophagy. Current research suggests that coffee does not stop autophagy. Research done in mice indicates that coffee actually stimulates autophagy in several tissues.

Lately, recent studies demonstrate that polyphenols, beneficial compounds found in plants, may play a role in inducing autophagy.

Polyphenols stimulate various pathways, which can lead to autophagy and a longer lifespan. Other polyphenols include quercetin, green tea catechins, and curcumin.

The following foods contain polyphenols that promote autophagy:. sales insidetracker. com Support center. All rights reserved. InsideTracker is a personalized nutrition model by Segterra.

What is autophagy? How do you induce autophagy? How long do you need to fast for autophagy? What foods inhibit autophagy? The following foods contain polyphenols that promote autophagy: Green tea Grape skin red wine Nuts Onions Apples Berries Turmeric Soybeans Milk thistle A summary of what we know about autophagy: Autophagy is a form of cellular housekeeping in which misfolded proteins, damaged organelles, and pathogens are degraded and removed from cells.

The lifespans of flies that instead fasted all day, eating only at night, did not change. For the researchers, the role of time was a big clue to how fasting is linked to longevity. They found that autophagy, a cell-cleaning process, kicks in after fasting, but only when fasting occurs during the night.

Autophagy Greek for self-eating is known to slow aging by cleaning up and recycling damaged components of the cell. Human cells use the same cell-cleaning processes, so the findings raise the possibility that behavioral changes or drugs that stimulate the cleaning process could provide people with similar health benefits, delaying age-related diseases and extending the lifespan.

Unlike dietary restriction, which reduces caloric intake, intermittent fasting does not. It merely limits feeding to specific hours of the day.

Nonetheless, intermittent fasting is far from effortless. It would be much easier to get the same health benefits if we could enhance autophagy pharmacologically, specifically at night. The potential for pharmacological applications may be realized if researchers continue to study how circadian regulation and autophagy control aging and lifespan.

In the current study, the researchers identified circadian clock components Tim, Per, Cyc, and Clk and essential autophagy components Atg1 and Atg8a as both necessary and sufficient for the anti-aging, lifespan-extending benefits of iTRF.

Facebook Linkedin RSS Twitter Youtube. Sign in. your username. your password. Forgot your password? Get help. Privacy Policy. Since fasting is a well-established mechanism for inducing autophagy, it seems likely that fasting-induced autophagy may play a critical role in limiting chemo-toxicity.

Fasting-induced upregulation of the autophagic process may render cells prepared to deal with a systemic challenge faced during chemotherapeutic induction. But importantly, this also raises the question whether fasting-induced autophagy may not similarly be protective to cancer cells.

Indeed, the observation that inhibition of autophagy sensitizes cancer cells to therapeutic interventions demonstrates that autophagy also has a key pro-survival function in numerous cancers 16 — However, cancer cells often demonstrate a comparatively lower capacity to induce autophagy, since the development of cancer is often associated with a defect in autophagic capacity.

As an example, oncogenes that are often upregulated in cancer e. This would suggest that, at least in some cancers, the differential stress response may in fact manifest from the inability of cancer cells to sustain autophagic processes as effectively as normal cells.

Also, many growth factors potently inhibit autophagy by promoting the utilization of exogenous nutrients The decrease in circulating growth factors may thus result in an upregulation of autophagy in normal cells, but not cancer cells that have developed insensitivity to external growth cues.

Thus, there is reason to suspect that host cells, which are more responsive to fasting cues, may upregulate autophagy to a greater extent than cancer cells.

Accumulating evidence indicates that the antineoplastic effect of various chemotherapeutic agents is not only dependent on their cytotoxic effects but also that such agents exert their therapeutic effect through their ability to reinstate immune surveillance after inducing ICD in cancer cells Mechanistically, certain chemotherapeutics e.

Another hallmark of ICD is the release of danger-associated molecules DAPMPs , such as ATP, various heat shock proteins, and signaling molecules e. Interestingly, autophagy has also been shown to enhance the immunogenicity of dying tumor cells by secretion HMGB1 Similarly, autophagy has been shown to play a critical role in mediating ICD through the release of ATP prior to apoptosis This suggests that the recruitment of the autophagic machinery e.

Strikingly, recent findings show that this may indeed be the case. Fasting 48 h or administering agents known to upregulate autophagy hydroxycitrate augments the antineoplastic properties of mitoxantrone and oxaliplatin, an effect which was not observed if cancer cells were implanted in immune-compromised mice, or if the critical autophagic gene Atg5 was silenced In particular, the role of autophagy-mediated ATP release is demonstrated by two observations.

First, in autophagy-deficient cells, ATP release is attenuated. Second, cancer cells overexpressing CD39, an ecto-ATPase that rapidly converts ATP to AMP, demonstrated a marked decrease in chemotherapeutic efficacy, which was reversed by intra-tumor administration of ATPase inhibitors. The observation that fasting-induced autophagy promotes ICD suggests novel mechanisms through which fasting may enhance chemotherapeutic efficacy.

Furthermore, autophagy also plays a critical role in epitope expression. The prototypical view where MHC II epitopes are derived from exogenous i.

While autophagy has a more established role in the expression of epitopes by MHC II 29 , recent evidence has implicated autophagy in the expression of epitopes by MHC I Macroautophagy provides a constant source of cytosolic proteins that fuse with MHC II loading compartments 29 , suggesting that fasting-induced autophagy may increase the presentation of cytosolic epitopes.

Supporting this view, autophagy, induced in vitro by starvation, enhances the expression of intracellular proteins on MHC II Short-term fasting has also been shown to enhance the mucosal-derived B lymphocyte response to an orally administered influenza vaccine Similarly, administration of the mTOR-inhibitor rapamycin enhances vaccine efficacy by promoting cross-strain protection Similar to the effects of autophagy induction in enhancing vaccine efficacy, upregulating autophagy prior to chemotherapy may enhance immunization against tumor antigens.

In fact, there is evidence that autophagy may play an important role in epitope presentation within an oncological context. As an example, autophagy, induced by either starvation or pharmacologically in antigen-donating cancer cells, enhances the cross-presentation of these antigens by dendritic cells These observations suggest that the role of autophagy in managing various infections and promoting vaccine efficacy are likely also important in reinstating anticancer immune response.

This then also suggests that fasting may mediate therapeutic effects by enhancing epitope expression resulting from an upregulation of autophagic processes. Initial findings from preclinical studies suggests that fasting my sensitize cancer cells to chemotherapeutic interventions 2.

As an example, though autophagy has been implicated in the unconventional secretion of IL-1β 36 , a well-known pro-inflammatory cytokine, autophagy may also inhibit the expression of IL-1β production by targeting the activated inflammasome for autophagic degradation In addition, autophagy may also promote immune evasion by cancer cells.

Similarly, inhibition of autophagy has also been shown to promote ICD in at least some tumors Autophagy has also been implicated as a mechanism by which cancer cells avoid NK-mediated lysis by targeting granzyme B released for autophagic degradation These observations demonstrate that autophagy may also play a role in mediating immune evasion by transformed cells.

Recently, evidence has emerged that fasting may also enhance the efficacy of oncolytic viruses OVs In normal cells, fasting increases the phosphorylation status of translation initiation factor eIF2α, resulting in a depression of protein synthesis; in contrast, cancer cells do not exhibit the same level of eIF2α phosphorylation.

Consequently, viral growth is inhibited in fasting-responsive normal cells as they downregulate the translational machinery required for viral replication, while cancer cells remain insensitive This may explain the sensitivity of cancer cells to the herpes simplex virus HSV compared to host cells when administered in a fasted state It is likely that fasting may also induce similar results in other OVs.

Since viruses are dependent on host replication machinery, fasting would suppress viral replication by downregulating cellular replication and translational activities. In contrast, cancer cells that are less responsive to fasting cues would maintain higher metabolic activity and thus be more susceptible to viral infections.

As an example, upregulating autophagy by means of fasting results in a dramatic suppression of viral infections in a variety of cell types This would suggest that fasting may preferentially sensitize autophagy-deficient cancer cells to HSV, as normal cells would be more resistant by virtue of the elevated levels of autophagy in cells responding to a fasted state.

Of note, an upregulation of autophagy may not be beneficial to all types of viruses since certain viral agents also subvert autophagic processes for replication and the non-lytic release of viral particles As an example, the hepatitis C virus is known to upregulate autophagy in hepatocytes, where the inhibition of autophagy in fact hampers viral replication as cells induce apoptotic cell death Indeed, the key role played by autophagy in cell-autonomous defense against viral infections has also generated interest as pathways that may be targeted for enhancing OV efficacy An upregulation of autophagy through fasting may thus either increase or decrease viral infectivity, since autophagy has different roles in the replication strategies of OVs.

Furthermore, viral subversion of autophagic processes is known to depend on the tissue type being infected This would suggest that the tissue of origin in cancer may also have an impact on the outcome of fasting-induced autophagy in OV therapy.

Intriguingly, recent evidence suggests that the evolution of drug resistance may also alter the role of autophagy in viral replication Thus, both tissue origin and the development of drug resistance are likely to have an impact on clinical trials where the role of fasting in OV therapy is evaluated.

Autophagy as a catabolic process plays a key immunological role in enhancing cell-autonomous defenses, and, as such, pathogens such as viruses have evolved various strategies both to inhibit and to subvert this process 44 , Consequently, it is likely that upregulation of autophagy may not be effective for all OVs or even counterproductive.

Therefore, it appears that fasting may have an impact on both viral and chemotherapeutic interventions via diverse mechanisms involving both an upregulation of autophagy and a decrease in circulating growth factors Figure 1.

Figure 1. Autophagy may remove cellular components damaged by antineoplastic therapies and also promote the reinstatement of immune surveillance against cancer cells. A Autophagy plays a key role in the clearance of damaged cellular components and organelles.

Removal of protein aggregates or damaged mitochondria may promote cell survival. B Autophagy is also involved in epitope expression. Exogenous antigens derived from cell bodies or secreted by cancer cells can be processed into epitopes to be loaded in MHC I and II loading compartments.

Similarly, endogenous epitopes processed by autophagy can be expressed by cancer cells, enhancing their immunogenic profile. C Fasting may also have an impact on the efficacy of oncolytic viral therapy.

Many viruses target diverse steps within the autophagic process for either viral subversion or inhibition of host antiviral response [reviewed by Chiramel et al.

Thus, autophagy may either promote or impede viral infectivity. Not illustrated, autophagy has also been implicated in the release of inflammatory mediators, such as IL-1β, ATP, and HMGB1, via secretory autophagy Observations in mice suggest that fasting may represent a cost-effective intervention that may greatly increase the therapeutic window.

However, it is not obvious how fasting protocols for mice would translate to humans. Mice have a large surface-to-body ratio with a metabolic rate vastly higher than that of humans 49 ; therefore, the effect of 48 h of fasting in mice would have far more pronounced effects in a rodent model compared to humans.

As an example, the rate of hepatic gluconeogenesis in mice is about This raises the question whether more extreme fasting protocols need to be implemented in patients to replicate more accurately the metabolic consequences seen in mice.

Prolonged fasting protocols that are necessary to induce a similar catabolic state in humans may not be feasible in many cancer patients who are already undernourished and lack the reserve capacity to tolerate prolonged bouts of fasting.

These considerations thus highlight the need to understand the mechanisms by which fasting may benefit patients. As an example, the involvement of autophagy as a key mediator behind the effect of fasting would predict that prolonged fasting may not be necessary, as autophagy is rapidly upregulated even after short-term fasting Also, the pharmacological activation of key pathways involved in the fasting response is an attractive alternative to direct fasting.

Additional studies are needed to identify the context in which fasting may be beneficial. As mentioned, there are contrasting findings on the role of autophagy in ICD.

Furthermore, it has been suggested that other interventions, such as radiotherapy, may also benefit from fasting regimes In this regard, radiotherapy has also been shown to induce ICD in a number of tumors Since autophagy can either inhibit or promote ICD, it is likely that fasting-induced autophagy may also alter the therapeutic outcome of radio therapy.

Fasting may also invoke mechanisms beyond modulating nutrient and growth factor levels. As an example, postprandial reabsorption of bile acids acts as singling molecules that could alter the effects of chemotherapy. Bile acids alter a range of immune and metabolic activities via farnesoid X receptor FXR Even in a fasted state, the pharmacological activation of FXR suppresses autophagy by attenuating the transcription of autophagic genes In addition, FXR also has an anti-inflammatory function As an example, FXR activation leads to the downregulation of monocyte chemoattractant protein-1 in macrophages It remains to be established whether FXR signaling also modulates other peripheral immune effects.

However, this does demonstrate that bile released in response to feeding may inhibit autophagy and also cause anti-inflammatory activity that may antagonize the mobilization of a robust immune response to cancer cells.

In this article, we have highlighted the potential protective role of fasting-induced autophagy as a mechanism by which cells cope with the adverse effects of chemotherapy. In addition, we have pointed out that since autophagy is also involved in immune responses it is possible that an upregulation of autophagy may have an impact on immune function and, in particular, help or hinder the reinstatement of immune surveillance against transformed cells.

Furthermore, fasting results in a range of physiological adaptations which may have an impact on the efficacy of chemotherapeutic agents. It is likely that the protective effects of fasting may be mediated by these processes operating in concert. A clear understanding of the mechanism invoked by fasting may lead to the development of pharmacological strategies that replicate these same processes.

Such therapies may be of particular importance in patients who are already undernourished or where nutrient deprivation is contraindicated. GN, SH, and A-ME wrote the manuscript. All the authors read and approved of the final version of the manuscript.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors acknowledge funding support from the Cancer Association of South Africa CANSA , the National Research Foundation NRF , and the Medical Research Council MRC of South Africa.

The authors also thank Ella Belcher for the professional language editing. Raffaghello L, Lee C, Safdie FM, Wei M, Madia F, Bianchi G, et al.

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