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. Learn about 8 strategies to help you stick with your weight loss resolution and achieve a better you. Discover the health benefits of walking, and how it can help you lose weight.

Learn more about the most common symptoms of menopause, and how LifeMD can help you manage them. It can be challenging to manage some of the uncomfortable symptoms of menopause.

Join LifeMD today and experience amazing healthcare, discounted labs and prescription medications plus around-the-clock access to medical guidance. By leveraging its proprietary technology platform, state medical group, and nationwide mail-order pharmacy network, LifeMD is increasing access to amazing healthcare that is affordable to everyone.

In all states, medical treatment from licensed providers is provided by the "LifeMD Affiliated P. The LifeMD Affiliated P. s are administratively led by LifeMD Southern Patient Medical Care, P.

LifeMD, Inc. provides a variety of administrative and management services to the LifeMD Affiliated P. s and can be reached at Table of Contents What is Autophagy? Why Should You Fast for Autophagy Induction? How Does Fasting Impact Autophagy?

The Best Fasting Strategies to Achieve Autophagy Balancing Autophagy Nutrient Intake Factors That Influence Autophagy When Fasting Should You See a Doctor About Autophagy Fasting? Where Can You Learn More About Autophagy and Fasting? Weight Management Autophagy Fasting: What You Need to Know Before Starting October 09, 4 mins.

Get prescription weight loss medication online. Find out if you're eligible for GLP-1s, and get started on your weight loss journey.

Get Started. What is Autophagy? Reduced risk of chronic diseases Autophagy has been associated with a reduced risk of chronic health issues, including heart disease, diabetes, and cancer. Key Point: How Does Autophagy Prevent Neurodegenerative Diseases?

Enhanced immune function Autophagy plays a critical role in immune system function by clearing pathogens and helping the body to create and deliver antibodies to cells. It can trigger autophagy in a few different ways: Reduced nutrient availability: During fasting, the body experiences a significant reduction in nutrient intake, which can activate autophagy.

The Best Fasting Strategies to Achieve Autophagy Implementing fasting helps to naturally prompt the body to initiate autophagy.

Intermittent fasting IF Intermittent fasting involves cycling between periods of eating and fasting. The diet, which involves eating normally for five days and restricting calorie intake on two nonconsecutive days.

Extended fasting Extended fasting typically involves fasting for longer periods, ranging from 24 hours to several days. Ready to achieve your weight loss goals?

Shed pounds with GLP-1 medication prescribed online by licensed healthcare providers. Key Point: How Long Should You Fast to Induce Autophagy? Below are some general guidelines that may be helpful: Short-term activation: Shorter fasting durations — such as 12 to 16 hours — can stimulate a moderate level of autophagy over a short period of time.

Tips for supporting autophagy beyond fasting There are a few different ways to initiate autophagy besides fasting. These include: Getting enough regular physical activity: Incorporate regular physical activity into your routine to support cellular health.

Factors That Influence Autophagy When Fasting Autophagy during fasting can be influenced by several factors. These may vary from person to person but generally include: Age: Autophagy tends to decline with age because cells become less responsive to biological signals.

What is the impact of exercise and hydration on autophagy fasting? Proper hydration is also essential for autophagy to function optimally.

Should You See a Doctor About Autophagy Fasting? Before implementing autophagy fasting, it's recommended to speak to a healthcare professional.

Privacy Policy. Join Now. 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.

Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy. Proc Natl Acad Sci U S A — PubMed Abstract CrossRef Full Text Google Scholar. Lee C, Raffaghello L, Brandhorst S, Safdie FM, Bianchi G, Martin-Montalvo A, et al.

Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy. Sci Transl Med ra Dorff TB, Groshen S, Garcia A, Shah M, Tsao-Wei D, Pham H, et al. Safety and feasibility of fasting in combination with platinum-based chemotherapy.

BMC Cancer de Groot S, Vreeswijk MP, Welters MJ, Gravesteijn G, Boei JJ, Jochems A, et al. The effects of short-term fasting on tolerance to neo adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study. Fontana L, Partridge L. Promoting health and longevity through diet: from model organisms to humans.

Cell — Fontana L, Partridge L, Longo VD. Extending healthy life span — from yeast to humans. Science —6. CrossRef Full Text Google Scholar.

Lee C, Safdie FM, Raffaghello L, Wei M, Madia F, Parrella E, et al. Reduced levels of IGF-I mediate differential protection of normal and cancer cells in response to fasting and improve chemotherapeutic index.

Cancer Res — Kroemer G, Mariño G, Levine B. Autophagy and the integrated stress response. Mol Cell — Di Gioacchino M, Petrarca C, Perrone A, Farina M, Sabbioni E, Hartung T, et al.

Autophagy as an ultrastructural marker of heavy metal toxicity in human cord blood hematopoietic stem cells. Sci Total Environ —8. Mazure NM, Pouyssegur J. Hypoxia-induced autophagy: cell death or cell survival? Curr Opin Cell Biol — Takahashi W, Watanabe E, Fujimura L, Watanabe-Takano H, Yoshidome H, Swanson PE, et al.

Kinetics and protective role of autophagy in a mouse cecal ligation and puncture-induced sepsis. Crit Care Zhou S, Starkov A, Froberg MK, Leino RL, Wallace KB. Cumulative and irreversible cardiac mitochondrial dysfunction induced by doxorubicin.

Cancer Res —7. PubMed Abstract Google Scholar. Kim I, Rodriguez-Enriquez S, Lemasters JJ. Selective degradation of mitochondria by mitophagy.

Arch Biochem Biophys — Gunst J, Derese I, Aertgeerts A, Ververs EJ, Wauters A, Van den Berghe G, et al. Insufficient autophagy contributes to mitochondrial dysfunction, organ failure, and adverse outcome in an animal model of critical illness.

Crit Care Med — Yorimitsu T, Klionsky DJ. Endoplasmic reticulum stress: a new pathway to induce autophagy. Autophagy —2. Maiuri M, Tasdemir E, Criollo A, Morselli E, Vicencio J, Carnuccio R, et al. Control of autophagy by oncogenes and tumor suppressor genes. Cell Death Differ — Lorin S, Hamaï A, Mehrpour M, Codogno P.

Autophagy regulation and its role in cancer. Semin Cancer Biol — Liu L, Yang M, Kang R, Wang Z, Zhao Y, Yu Y, et al. HMGB1-induced autophagy promotes chemotherapy resistance in leukemia cells.

Leukemia — Lum JJ, Bauer DE, Kong M, Harris MH, Li C, Lindsten T, et al. Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Galluzzi L, Buque A, Kepp O, Zitvogel L, Kroemer G.

Immunological effects of conventional chemotherapy and targeted anticancer agents. Cancer Cell — Gardai SJ, McPhillips KA, Frasch SC, Janssen WJ, Starefeldt A, Murphy-Ullrich JE, et al. Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte.

Garg AD, Galluzzi L, Apetoh L, Baert T, Birge RB, Bravo-San Pedro JM, et al. Molecular and translational classifications of DAMPs in immunogenic cell death. Front Immunol Thorburn J, Horita H, Redzic J, Hansen K, Frankel AE, Thorburn A.

Autophagy regulates selective HMGB1 release in tumor cells that are destined to die. Michaud M, Martins I, Sukkurwala AQ, Adjemian S, Ma Y, Pellegatti P, et al. Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice. Science —7. Pietrocola F, Pol J, Vacchelli E, Rao S, Enot DP, Baracco EE, et al.

Caloric restriction mimetics enhance anticancer immunosurveillance. Ponpuak M, Mandell MA, Kimura T, Chauhan S, Cleyrat C, Deretic V. Secretory autophagy.

Norbury CC, Hewlett LJ, Prescott AR, Shastri N, Watts C. Class I MHC presentation of exogenous soluble antigen via macropinocytosis in bone marrow macrophages. Immunity — Paludan C, Schmid D, Landthaler M, Vockerodt M, Kube D, Tuschl T, et al. Endogenous MHC class II processing of a viral nuclear antigen after autophagy.

Schmid D, Pypaert M, Münz C. Antigen-loading compartments for major histocompatibility complex class II molecules continuously receive input from autophagosomes. Chemali M, Radtke K, Desjardins M, English L. Alternative pathways for MHC class I presentation: a new function for autophagy.

Cell Mol Life Sci — Dengjel J, Schoor O, Fischer R, Reich M, Kraus M, Müller M, et al. Autophagy promotes MHC class II presentation of peptides from intracellular source proteins. Proc Natl Acad Sci U S A —7. Trollmo C, Verdrengh M, Tarkowski A.

Fasting enhances mucosal antigen specific B cell responses in rheumatoid arthritis. Ann Rheum Dis —4. Keating R, Hertz T, Wehenkel M, Harris TL, Edwards BA, McClaren JL, et al.

The kinase mTOR modulates the antibody response to provide cross-protective immunity to lethal infection with influenza virus. Nat Immunol — Li Y, Wang LX, Yang G, Hao F, Urba WJ, Hu HM. Efficient cross-presentation depends on autophagy in tumor cells. Fonteneau JF, Brilot F, Munz C, Gannage M.

J Immunol —

Intermittent fasting, the practice of going without food for some period of time, and caloric restriction are powerfully neuroprotective. Intermittent fasting increases autophagy, a metabolic process that eliminates cell waste that may be responsible for many of the effects of aging. Studies have demonstrated that fasting can help prevent heart disease, speed fat loss, and slow or reverse aging.

Intermittent or short-term fasting, as well as exercise, are known to increase growth hormone release and generation of healthy tissue, leading to improvements in the body over time.

In this video, Neurology Solutions Movement Disorders Center Medical Director Dr. Robert Izor explains the importance of nutrition and its correlation with metabolic enhancement for neurodegeneration MEND. Completed in vascular structures called lysosomes, autophagy reduces inflammation and lowers insulin levels, allowing for the breakdown of fat.

Cells also use autophagy to rid the body of damaged cell components. Autophagy is shut down dramatically after consuming food. Glucose, insulin or decreased glucagon , and proteins all turn off this self-cleaning process.

Likewise, growth hormones and other anabolic steroid hormones diminish gradually with age, also contributing to loss of healthy tissue function.

A article published in Nature explains that autophagy is a natural process that responds to this problem. During autophagy, the cells remove these unwanted molecules and dysfunctional parts. Sometimes, autophagy destroys some of these molecules and parts. Other times, the cell recycles these parts into new components.

Research has linked autophagy with several health effects, but this cellular process is complex, so it can be challenging to draw conclusions. For instance, a recent study surveys existing research into autophagy and cancer. It finds that while autophagy can help to stall the development of cancer cells, it may also promote their growth, depending on the stage of the tumor.

Researchers are also interested in the connection between autophagy and liver health. A review article explored the ways autophagy may help protect liver cells from drug- and alcohol-induced liver injury.

Other research states that autophagy plays a role in many liver functions and could prevent the progression of several liver conditions, including:.

However, the majority of studies on autophagy have taken place in test tubes or animal models. As the authors of the research above argue, it is necessary to carry out more research in humans to determine how autophagy can influence treatment.

Autophagy also seems to play an essential role in the immune system by cleaning out toxins and infectious agents.

There is evidence that autophagy may improve the outlook for cells with infectious and neurodegenerative diseases by controlling inflammation. Another review article explains that autophagy helps to protect cells against incoming microbes. Autophagy occurs naturally within the body, but many people wonder if they could induce autophagy using specific triggers.

Fasting is a possible trigger of autophagy. When somebody fasts, they voluntarily go without food for extended periods — hours or sometimes a day or more. Fasting is different from traditional calorie restriction.

When a person restricts their calories, they reduce their regular intake of food. Fasting may or may not result in calorie restriction, depending on how much food a person consumes during feeding periods.

A review of the existing research strongly suggests that both fasting and calorie restriction can induce autophagy. Although there is some evidence of this process occurring in humans, most of these studies involved non-human animals.

When a person limits the amount of food that goes into their body, their cells receive fewer calories than they need to function correctly. When this happens, the cells must work more efficiently.

Scientists are unsure about which cells respond to fasting and calorie restriction in this way, however. People trying to induce autophagy by fasting should be aware that this may not target fat cells, for example.

Researchers are still debating whether fasting can induce autophagy in the brain. At least one animal study suggests that short term fasting can induce autophagy in brain cells. Fasting and calorie restriction both trigger autophagy by putting cells under stress.

However, researchers believe that there may be other ways to induce autophagy. When people exercise, the components of their cells become damaged and inflamed. The authors of one paper explain that our cells respond to this problem with autophagy.

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.

First, we took images of specific area Q-Capture Pro7, Olympus and determine the location of EGFP-LC3 vesicles. The details are described in Figure legends Supplementary Figure 3. The actual p-values are supplied in Supplementary Information Supplementary Table 1.

All experimental procedures were performed in accordance with the protocols approved by the Committees on Human Ethics and Animal Experiments of Tokyo Medical and Dental University C6, A, A. How to cite this article : Chen, X.

et al. Fasting activates macroautophagy in neurons of Alzheimer's disease mouse model but is insufficient to degrade amyloid-beta. Nixon, R. Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study. J Neuropathol Exp Neurol 64, — Article Google Scholar.

Yu, W. J Cell Biol , 87—98 Article CAS Google Scholar. Lipinski, M. Proc Natl Acad Sci USA , — Article ADS CAS Google Scholar. Lu, T. Nature , — Jiang, P. Autophagy and human diseases. Cell Res 24, 69—79 Trinh, J.

Advances in the genetics of Parkinson disease. Nat Rev Neurol. Kitada, T. Mutations in the parkin gene cause autosomal recessive juvenile Parkinsonism. Valente, E. Localization of a novel locus for autosomal recessive early-onset Parkinsonism, PARK6, on human chromosome 1pp Am J Hum Genet 68, — Science , — Hanein, S.

Identification of the SPG15 gene, encoding spastizin, as a frequent cause of complicated autosomal-recessive spastic paraplegia, including Kjellin syndrome.

Am J Hum Genet 82, — Fecto, F. SQSTM1 mutations in familial and sporadic amyotrophic lateral sclerosis. Arch Neurol 68, — Mizushima, N. In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker.

Mol Biol Cell 15, — Ravikumar, B. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease.

Nat Genet 36, — Tsvetkov, A. Potent and reliable autophagy induction in neurons. Proc Natl Acad Sci USA , E Hara, T. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Komatsu, M. Loss of autophagy in the central nervous system causes neurodegeneration in mice.

Hoshino, M. Ptf1a, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum. Neuron 47, — Kuma, A.

Autophagy 3, — Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell , — Desnick, R. Enzyme replacement and enhancement therapies: lessons from lysosomal disorders. Nat Rev Genet 3, — Shoji, M. JNK activation is associated with intracellular beta-amyloid accumulation.

Mol Brain Res 85, — Alirezaei, M. Short-term fasting induces profound neuronal autophagy. Autophagy 6, — Kang, J. Aβ dynamics are regulated by orexin and the sleep-wake cycle. Oakley, H. J Neurosci 26, — Kabeya, Y. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.

EMBO J 19, — Download references. We also thank Dr. Kazuhiko Tagawa for support of ethics approval, technical support and discussion. Department of Neuropathology, Medical Research Institute, Tokyo Medical and Dental University, Yushima, , Tokyo, Bunkyo-ku, Japan. Center for Brain Integration Research, Tokyo Medical and Dental University, Yushima, , Tokyo, Bunkyo-ku, Japan.

You can also search for this author in PubMed Google Scholar. and K. performed the experiments and wrote the paper. statistically analyzed the data. designed the research and wrote the paper. This work is licensed under a Creative Commons Attribution 4.

Reprints and permissions. Chen, X. Sci Rep 5 , Download citation. Received : 09 March Accepted : 17 June Published : 14 July Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative. Cellular and Molecular Life Sciences Acta Neuropathologica Communications By submitting a comment you agree to abide by our Terms and Community Guidelines.

If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Skip to main content Thank you for visiting nature. nature scientific reports articles article. Download PDF. Subjects Alzheimer's disease Macroautophagy.

Introduction Autophagy, especially macroautophagy mediated by autophagosome, has been implicated in various neurodegenerative diseases including AD. Results A new in vivo imaging of macroautophagy in the brain of living animals based on two-photon microscopy To visualize autophagic vacuoles in living neurons in the brain, we generated lentiviral vector expressing EGFP-LC3.

Figure 1. Full size image. Figure 2. In vivo imaging of autophagosome in AD model and control mice a Experimental protocol of the in vivo time-lapse imaging to test the effect of fasting on autophagosome formation. Figure 3. Figure 4. Figure 5. Discussion Our study firstly proved that macroautophagy was actually induced by starvation in mouse neurons in vivo.

Methods AD model mice 5xFAD mice and control mice male, 3 month old were used for the experiments in this study. In vivo imaging with two-photon microscopy Two-photon imaging of autophagy was performed using a laser-scanning microscope system FVMPE2 Olympus, Japan equipped with an upright microscope BX61WI, Olympus, Japan , a water-immersion objective lens XLPlanN25xW; numerical aperture, 1.

Ethics All experimental procedures were performed in accordance with the protocols approved by the Committees on Human Ethics and Animal Experiments of Tokyo Medical and Dental University C6, A, A. Additional Information How to cite this article : Chen, X. References Nixon, R.

Article Google Scholar Yu, W. Article CAS Google Scholar Lipinski, M. Article ADS CAS Google Scholar Lu, T. Article ADS CAS Google Scholar Jiang, P.

Article CAS Google Scholar Trinh, J. Article CAS Google Scholar Kitada, T. Article ADS CAS Google Scholar Valente, E. Article CAS Google Scholar Valente, E. Article ADS CAS Google Scholar Hanein, S. Article CAS Google Scholar Fecto, F.

Article Google Scholar Mizushima, N. Article CAS Google Scholar Ravikumar, B. Article CAS Google Scholar Tsvetkov, A. Article ADS CAS Google Scholar Hara, T. Article ADS CAS Google Scholar Komatsu, M. Article ADS CAS Google Scholar Hoshino, M.

Article CAS Google Scholar Kuma, A. Article CAS Google Scholar J. Article CAS Google Scholar Desnick, R. Article CAS Google Scholar Shoji, M. Article CAS Google Scholar Alirezaei, M.

Article Google Scholar Kang, J. Article ADS CAS Google Scholar Oakley, H. Article CAS Google Scholar Kabeya, Y. Article CAS Google Scholar Download references. Author information Author notes Chen Xigui and Kondo Kanoh contributed equally to this work. View author publications.

Ethics declarations Competing interests The authors declare no competing financial interests. Electronic supplementary material. Supplementary Information.

Intermittent or short-term fasting, as well as exercise, are known to increase growth hormone release and generation of healthy tissue, leading to improvements in the body over time. In this video, Neurology Solutions Movement Disorders Center Medical Director Dr.

Robert Izor explains the importance of nutrition and its correlation with metabolic enhancement for neurodegeneration MEND. Completed in vascular structures called lysosomes, autophagy reduces inflammation and lowers insulin levels, allowing for the breakdown of fat.

Cells also use autophagy to rid the body of damaged cell components. Autophagy is shut down dramatically after consuming food. Glucose, insulin or decreased glucagon , and proteins all turn off this self-cleaning process. Likewise, growth hormones and other anabolic steroid hormones diminish gradually with age, also contributing to loss of healthy tissue function.

During starvation, cells break down proteins and non-essential components and reuse them for energy. Fasting also increases growth hormone release.

Autophagy works to remove substandard subcellular parts and unused proteins that can accumulate and cause inflammation and oxidative stress. Many neurodegenerative conditions have some degree of mitochondrial dysfunction in common.

The mitochondria in the cells produce 90 percent of the energy needed to support organ function and sustain life. As we age, we no longer recycle damage as readily. Normalizing the autophagy system could theoretically help damaged cells clear out toxic accumulated proteins. Doctors therefore recommend fasting for short periods to activate this system as well as increase the number and quality of mitochondria.