Fasting and autophagy

The effect of fasting on autophagy induction Autophagy - the Novel Prize work by Japanese Researcher Dr. Ohsumi

Human being requires about 200 – 300 g of protein per day to live. On the other hand, human being takes only about 80 g of protein orally. The rest of protein is taken by cells through the process called autophagy, degradation and reutilization of unnecessary protein.

With this mechanism, the balance of synthesis and degradation of protein in our body is always kept constant. For example, human being can live about one month with only water, thanks to this mechanism.

In 2016, the Novel Prize in Physiology or Medicine was awarded to Japanese Researcher Dr. Yoshinori Ohsumi for elucidating the mechanisms underlying autophagy. Autophagy, a coined term meaning self-eating, is a “intracellular recycling system” that plays important roles in maintaining homeostasis and preventing nutritional, metabolic, and infection-mediated stresses.

Dr. Ohsumi was the world’s first to observe the autophagy through microscope using yeast cells under fasting conditions in 1988. He found that cytoplasmic components such as organelles and proteins are taken in by a particular organelle, the vacuole. He recalls, “It was an awe-inspiring sight that I could have kept watching for hours. For me, that was the breakthrough moment”.

Modulation of autophagy as a therapeutic target

Autophagy maintains normal cellular physiology to eliminate damaged organelles, long-lived misfolded proteins and invading pathogens, under stressful conditions, such as carcinogenic, infectious, degenerative, and deleterious agents. Thus, its dysregulation is shown to cause multiple human diseases. For example, neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Huntington’s diseases are triggered by the accumulation of abnormal protein resulting from disrupted autophagy in the nerve cells of the brain. As another example, fatty liver is shown to be related with the accumulation of protein called Rubicon, that suppresses autophagy. Thus, modulation of autophagy can be a potential therapeutic target for a diverse range of diseases, cancers and infectious diseases.

The effect of fasting by autophagy induction

Traditionally, fasting has been considered to have anti-aging effect. Since inhibition of autophagy pathway attenuates the anti-aging effects of fasting, it has been proposed that autophagy plays an important role in fasting and calorie restriction mediated anti-aging effect. Among several stress stimuli inducers of autophagy, fasting and calorie restriction are the most potent non-genetic autophagy stimulators. As a healthy practice, calorie restriction in the form of intermittent fasting in several clinical settings has been reported to promote several health benefits, including priming of immune response. Modulation of autophagy by intermittent fasting or calorie restriction is thus intensively investigated in the area including ischemia-reperfusion injury of the myocardium, prevention of COVID-19, and cancer treatment.

The effect of fasting on cancer therapy

The role of autophagy in cancer is complex, and its function may vary according to several biological factors, progression stage, and oncogene activation and inactivation. In this respect, autophagy can be related to either promotion or suppression of tumor growth and metastasis. Generally, cancer cells utilize autophagy for their metabolic needs even in hypoxic condition, thus inhibition of autophagy usually leads to induction of tumor cell death. However, to date, no clinical trials have demonstrated that inhibition of autophagy as a reliable therapeutic method for patients under cancer therapy. On the other hand, protocols targeting autophagy induction instead of autophagy blockade are under intense investigation in oncology.

Among those, intermittent fasting (alternate day fasting > 16hours) and calorie restriction (20-40%) are most investigated. Studies in in vivo and in vitro models have shown that intermittent fasting improved both chemotherapeutic response of many cytotoxic agents and radiologic sensitivity in models of most major cancers. Fasting in combination with cytotoxic agents is known to elicit differential response in normal and cancer cells, a phenomenon called differential stress resistance. When nutrients are absent, normal cells inactivate growth factor signaling while cancer cells don’t, thus becoming more vulnerable to cytotoxic treatment. Though the molecular mechanism of intermittent fasting has yet been cleared, in vitro data showed autophagy induction. The results of studies suggest that intermittent fasting can be applied to reduce side effects and toxicity in patients undergoing chemotherapy.

オートファジー誘導に対する断食の効果

オートファジー-大隅博士によるノーベル賞研究

人間が生きるためには、1日あたり約200〜300gのタンパク質が必要です。一方、人間は口から約80gのタンパク質しか摂取しません。残りのタンパク質は、オートファジー、すなわち不要なタンパク質の分解、再利用と呼ばれるプロセスを通じて細胞に取り込まれます。

このメカニズムにより、私たちの体内のタンパク質の合成と分解のバランスは常に一定に保たれます。たとえば、このメカニズムのおかげで、人間は水だけで約1ヶ月生きることができます。

2016年には、オートファジーの根底にあるメカニズムを解明したことで、日本の研究者である大隅良典博士にノーベル生理学・医学賞が授与されました。オートファジーは、自食を意味する造語であり、恒常性を維持し、栄養、代謝、また感染などに対するストレス防御に重要な役割を果たす「細胞内リサイクルシステム」です。

大隅良典博士は、1988年に絶食中の酵母細胞を用いてオートファジーの顕微鏡による観察を世界で初めて行いました。オルガネラやタンパク質などの細胞質成分が特定のオルガネラである空胞に取り込まれることを発見しました。彼は次のように回想します。「それは畏敬の念を起こさせる光景で、私は何時間も見続けることが出来ました。私にとって、それは画期的な瞬間でした。」

治療標的としてのオートファジーの調節

オートファジーは、発がん、感染、変性、および有害な病原体といったストレス条件下で、損傷した細胞小器官、老化し折りたたみ異常のあるタンパク質、および侵入する病原体を排除することによって正常な細胞生理学を維持します。したがって、その機能不全は、さまざまな病気を引き起こすことが示されています。たとえば、アルツハイマー病、パーキンソン病、ハンチントン病などの神経変性疾患は、脳の神経細胞におけるオートファジーの不全による異常なタンパク質の蓄積によって引き起こされます。別の例としては、脂肪肝は、オートファジーを抑制するルビコンと呼ばれるタンパク質の蓄積に関連していることが示されています。このようにオートファジーの調節は、さまざまな疾患、癌、および感染症の潜在的な治療標的として期待されています。

オートファジー誘導による断食の効果

昔から、断食は老化防止効果があると考えられてきました。オートファジー経路の阻害は絶食の老化防止効果を弱めるので、オートファジーは断食およびカロリー制限を介する老化防止効果において重要な役割を果たすことが示唆されています。オートファジーを誘発するいくつかのストレス刺激のうち、絶食とカロリー制限は最も強力な非遺伝子的オートファジー誘導因子です。健康的な習慣として、いくつかの臨床設定における断続的断食の形でのカロリー制限は、免疫応答のプライミングを含むいくつかの健康上の利点を促進することが報告されています。例えば断続的断食またはカロリー制限によるオートファジーの誘導は、心筋の虚血再灌流障害、COVID-19の予防、および癌治療を含む領域で精力的に研究されています。

がん治療に対する断食の影響

癌におけるオートファジーの役割は複雑であり、その機能は、いくつかの生物学的要因、進行段階、および癌遺伝子の活性化と不活性化によって異なる可能性があります。この点で、オートファジーは腫瘍の成長と転移の促進または抑制のいずれかに関連している可能性があります。一般に、癌細胞は、低酸素状態においても代謝の必要性のためにオートファジーを利用するため、オートファジーの阻害は通常、腫瘍細胞死の誘導につながります。しかし、これまでのところ、癌治療中の患者にとって信頼できる治療法としてオートファジーの阻害を実証した臨床試験はありません。一方、オートファジー阻害の代わりにオートファジー誘導を標的とするプロトコルは、腫瘍学において広く研究されています。

それらの中で、断続的断食(隔日断食> 16時間)とカロリー制限(20-40%)が最も研究されています。In vivoおよびin vitroモデルでの研究で、断続的絶食が多くの細胞毒性薬による化学療法反応、また多くの主要な癌モデルにおける放射線感受性の両方を改善したことが示されています。細胞毒性薬と組み合わせた絶食は、正常細胞と癌細胞で異なる反応を誘発することが知られており、これはストレス耐性格差と呼ばれる現象です。栄養素が存在しない場合、正常細胞は成長因子シグナル伝達を不活性化しますが、癌細胞はそうではないため、細胞毒性治療に対してより脆弱になります。断続的断食の分子メカニズムはまだ解明されていませんが、in vitroデータはオートファジー誘導を証明しました。研究の結果は、化学療法を受けている患者の副作用と毒性を減らすために断続的断食を適用できることを示唆しています。

Book an appointment

Related Services

ERCP

A cutting-edge medical technique that plays a crucial role in diagnosing and treating disorders of the bile ducts, pancreas, and gallbladder....

Liver Elastography

Liver Elastography – an advanced medical imaging technique designed to assess the health of your liver with precision and non-invasiveness....

Abdominal Pain

Abdominal pain can be a symptom of a wide range of medical conditions and can manifest in different ways depending on the...

Colorectal Cancer

Colorectal cancer (CRC) is a type of cancer that affects the colon or rectum. It can develop from small growths called polyps in...

Stomach Cancer

Stomach cancer, also known as gastric cancer, can cause a range of symptoms. However, it's important to note that not everyone...

Liver cancer

Liver cancer is a serious and potentially life-threatening condition that requires prompt diagnosis and treatment....

Colon polyp

Colon polyps are usually detected during a routine colonoscopy. During the procedure, a long, flexible tube with a camera on the...

Pancreatic Cancer

Pancreatic cancer often does not cause symptoms in its early stages....

Related Posts

Alcohol and Digestive Health: The Impact on Your Gut

The gastrointestinal (GI) tract, commonly known as the gut, plays a pivotal role in the digestion and absorption of nutrients,...

Crohn’s Disease and Ulcerative Colitis: Living with Inflammatory Bowel Diseases

Living with an inflammatory bowel disease (IBD) like Crohn's disease or ulcerative colitis can be challenging. ...

Maintaining a Healthy Gut: Tips for Promoting Digestive Wellness

Your gut, often referred to as your "second brain," is a hub of activity crucial to your overall health and...

Understanding the Gastrointestinal System: How Your Digestive Tract Works

The digestive system, often called the gastrointestinal (GI) system, is a marvel of biological engineering. Its primary function is to...

Top 10 Constipation Side Effects You Should Be Aware Of

Constipation is one of the most common gastrointestinal disorders that causes an individual to have difficulty passing stool and ...

Colorectal Cancer

Colorectal cancer (CRC) is the third most commonly diagnosed cancer among men and the second...

Trusted in Google Reviews

Hear What Our Customers Have to Say - Testimonials

 Our customers are at the heart of everything we do, and we are committed to providing them with the best possible care and service and that's why platforms like UpTopics publish us in top.

"Dr. Ashraf Kamel is one of the best uerologist. His knowledge, expertise and approach is amazing. His confidence really helps u get moving and give u the hope that u want. Thank you so much Dr. Ashraf and German Medical Center."
Aakash Gupta

(4.5)

Based on 174 Google Reviews

Ready to prioritize your health?

Fill out our easy online form to book an appointment with German Medical Center. Our team of experts is dedicated to providing you with personalized care and guidance every step of the way. Don't wait, take charge of your well-being and schedule your appointment now!