Fasting triggers stem cell regeneration of damaged, old immune system

In the first evidence of a natural intervention triggering stem cell-based regeneration of an organ or system, a study shows that cycles of prolonged fasting not only protect against immune system damage — a major side effect of chemotherapy — but also induce immune system regeneration, shifting stem cells from a dormant state to a state of self-renewal.

In both mice and a Phase 1 human clinical trial involving patients receiving chemotherapy, long periods of not eating significantly lowered white blood cell counts. In mice, fasting cycles then “flipped a regenerative switch,” changing the signaling pathways for hematopoietic stem cells, which are responsible for the generation of blood and immune systems, the research showed.

Learn more: Fasting-mimicking diet

• A low-calorie fasting-like diet, plus chemotherapy, enables the immune system to recognize and kill skin and breast cancer cells, according to a new USC-led study on mice.

• Evidence is mounting that a diet mimicking the effects of fasting has health benefits beyond weight loss, with a new USC-led study indicating that it may reduce symptoms of multiple sclerosis.

• A diet that mimics fasting appears to slow againt.

The study has major implications for healthier aging, in which immune system decline contributes to increased susceptibility to disease as people age. By outlining how prolonged fasting cycles — periods of no food for two to four days at a time over the course of six months — kill older and damaged immune cells and generate new ones, the research also has implications for chemotherapy tolerance and for those with a wide range of immune system deficiencies, including autoimmunity disorders.

“We could not predict that prolonged fasting would have such a remarkable effect in promoting stem cell-based regeneration of the hematopoietic system,” said corresponding author.

“When you starve, the system tries to save energy, and one of the things it can do to save energy is to recycle a lot of the immune cells that are not needed, especially those that may be damaged,” Longo said. “What we started noticing in both our human work and animal work is that the white blood cell count goes down with prolonged fasting. Then when you re-feed, the blood cells come back. So we started thinking, well, where does it come from?”

Fasting cycles

Prolonged fasting forces the body to use stores of glucose, fat and ketones, but it also breaks down a significant portion of white blood cells. Longo likens the effect to lightening a plane of excess cargo.

During each cycle of fasting, this depletion of white blood cells induces changes that trigger stem cell-based regeneration of new immune system cells. In particular, prolonged fasting reduced the enzyme PKA, an effect previously discovered by the Longo team to extend longevity in simple organisms and which has been linked in other research to the regulation of stem cell self-renewal and pluripotency — that is, the potential for one cell to develop into many different cell types. Prolonged fasting also lowered levels of IGF-1, a growth-factor hormone that Longo and others have linked to aging, tumor progression and cancer risk.

“PKA is the key gene that needs to shut down in order for these stem cells to switch into regenerative mode. It gives the OK for stem cells to go ahead and begin proliferating and rebuild the entire system,” explained Longo, noting the potential of clinical applications that mimic the effects of prolonged fasting to rejuvenate the immune system. “And the good news is that the body got rid of the parts of the system that might be damaged or old, the inefficient parts, during the fasting. Now, if you start with a system heavily damaged by chemotherapy or aging, fasting cycles can generate, literally, a new immune system.”

Prolonged fasting also protected against toxicity in a pilot clinical trial in which a small group of patients fasted for a 72-hour period prior to chemotherapy, extending Longo’s influential past research.

“While chemotherapy saves lives, it causes significant collateral damage to the immune system. The results of this study suggest that fasting may mitigate some of the harmful effects of chemotherapy,” said co-author of the study. “More clinical studies are needed, and any such dietary intervention should be undertaken only under the guidance of a physician.”

“We are investigating the possibility that these effects are applicable to many different systems and organs, not just the immune system,” said Longo, whose lab is in the process of conducting further research on controlled dietary interventions and stem cell regeneration in both animal and clinical studies.

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Here's why cold induces tooth pain, hypersensitivity; some remedies for it

A team of researchers from Boston University have uncovered a new function for odontoblasts, the cells that form dentin, the shell beneath the tooth's enamel that encases the soft dental pulp containing nerves and blood vessels.

The results of the study were published in the journal of Science Advances.

"We found that odontoblasts, which support the shape of the tooth, are also responsible for sensing cold," says pathologist Jochen Lennerz, MD, PhD, one of the paper's senior authors and medical director of the Center for Integrated Diagnostics at Massachusetts General Hospital (MGH). "This research contributes a new function to this cell, which is exciting from a basic-science standpoint. But we now also know how to interfere with this cold-sensing function to inhibit dental pain."

Teeth that hurt from exposure to cold can occur for many reasons. Many people have experienced intense pain from cold when they have a hole in a tooth from an untreated cavity, for example. But teeth can also become very sensitive to cold from gum erosion due to aging. Some cancer patients treated with platinum-based chemotherapies have extreme cold sensitivity all over their bodies. "A breeze on the face registers as extreme pain in the teeth, which may even cause some patients to stop therapy," says Lennerz.

Tooth pain has been notoriously difficult to study. A tooth's hardness makes it a challenging tissue to study and inducing tooth pain in humans requires opening the tooth. The team of researchers, therefore, conducted experiments on mice whose molars were drilled under anaesthesia. Mice with dental injuries manifest pain with their behaviour; they drink up to 300 per cent more sugar water than their littermates without dental injuries, for example. In previous research, the team of investigators had discovered TRCP5, a protein encoded by the TRCP5 gene that is expressed in nerves in many parts of the body. Their earlier discovery allowed the researchers to zero in on TRCP5 as a mediator of pain from cold.

By studying genetically altered mice that did not have the TRCP5 gene, the researchers found that the mice with injured teeth did not manifest the increased drinking behaviour and behaved like mice without dental injuries.

"We now have definitive proof that the temperature sensor TRCP5 transmits cold via the odontoblast and triggers nerves to fire, creating pain and cold hypersensitivity," says Lennerz. "This cold sensitivity may be the body's way to protect a damaged tooth from additional injury."

Specifically, in response to cold, the TRCP5 protein opens channels in the membrane of odontoblasts, enabling other molecules, such as calcium, to enter and interact with the cell. If the tooth's pulp is inflamed from a deep cavity, for example, TRCP5 is overabundant, causing increased electrical signaling via the nerves emerging from the root of the tooth and running to the brain, where pain is perceived. When gums recede from ageing, teeth can become hypersensitive because the odontoblasts are sensing cold in a newly exposed region of the tooth. "Most cells and tissues slow their metabolism in the presence of cold, which is why donor organs are put on ice," says Lennerz. "But TRPC5 makes cells more active in cold, and the odontoblasts' ability to sense cold via TRPC5 makes this discovery so exciting."

Lennerz confirmed the presence of the TRPCS protein in extracted human teeth, which was a technical tour de force. "Our teeth aren't meant to be cut into ultra-thin layers so they can be studied under the microscope," says Lennerz, who first had to decalcify the teeth and put them in epoxy resin before slicing them and identifying the TRPC5 channels in the odontoblasts.

The research team also identified a pharmacological target for minimizing tooth sensitivity to cold. For centuries, oil of cloves has been used as a remedy for tooth pain. The active agent in the oil of cloves is eugenol, which happens to block TRCP5. Toothpaste containing eugenol are already on the market, but the findings of this study may lead to more potent applications to treat teeth that are hypersensitive to cold. And there may be novel applications for eugenol, such as treating patients systemically for extreme cold sensitivity from chemotherapy. "I'm excited to see how other researchers will apply our findings," says Lennerz. 

 

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What all one needs to know about Epileptic seizure

According to a recent study, this is the most common neurological emergency in children and seizures are potentially fatal. In fact, up to 5 percent of affected children succumb to it and a third suffer brain damage. The longer the seizure, the greater the chance of long-term complications.
Epilepsy is a neurological disorder where abnormal brain activity induces unprovoked seizures. It can affect anyone regardless of sex, race, age and cultural background. Though uncommon, this condition can sometimes cause fatal epileptic seizures.

Medications can control the seizures to a certain extent. However, surgical intervention may be needed in some cases. Most people, however, have to be on medication throughout their lives to control seizures but, for others, it becomes infrequent and then stops completely as they age. One peculiarity about this disease is that it is more common in young children and the older generation.

WHAT CAN AN EPILEPTIC SEIZURE DO?

It can cause temporary confusion, uncontrollable jerking movements of the arms and legs, loss of consciousness or awareness and psychic symptoms like fear, anxiety or déjà vu. It can also make a person stare at the same spot for the duration of seizure. Though symptoms vary from person to person, it usually remains the same for each person.

WHEN DOES AN EPILEPTIC SEIZURE BECOME FATAL?

Epileptic seizures are usually not fatal and only 1 in 1000 patients die because of it, suggests some estimate. However, sometimes, it can cause death. Let us look at a few conditions that can cause fatal epileptic seizures.

Lafora disease

According to researchers  Lafora disease, an inherited form of epilepsy that results in death by the age of 30, can be caused by mutations in a gene that regulates the concentration of the protein laforin.  In Lafora disease, a person has normal development for the first decade of life, followed by an initial seizure in the second decade. These seizures become progressively worse and eventually it causes early dementia and death within 10 years of onset. Medications can help contain the initial symptoms, but there is no long-term treatment or cure yet.

Status epilepticus

This condition increases the risk of permanent brain damage and death.Usually, a seizure will stop by itself. But, at times, you may experience a long seizure or a series of seizures without recovering in between. If this carries on for 5 minutes or more, it is called status epilepticus.

What you can do: If this happens in a tonic-clonic seizure where people fall down and shake, you need to get medical help immediately. If a convulsive seizure carries on for more than 30 minutes,it can cause brain damage and even death. Call an ambulance if the patient has trouble breathing after the seizure or if one seizure immediately follows another with no recovery in between. You also need to act fast if the seizure lasts two minutes longer than usual for that person and if the seizure lasts for five minutes or more.

Sudden unexpected death in epilepsy (SUDEP)

This is rare, but the risk is there. Only about 1 per cent or 1 in 1000 epilepsy patients die of SUDEP. Death usually occurs suddenly when the patient is sleeping, either during or after a seizure and the cause is often inconclusive. Most experts are of the view that this could be due to heart or respiratory health.The risk is greater in patients who have frequent tonic-clonic seizures or those whose seizures are not controlled by medications. This is more common in people with poorly controlled epilepsy and is rarely seen in children.

Though the exact cause of SUDEP is not known, experts suspect that it could be due to pauses in breathing during a seizure, which can cause death if they go on too long. A convulsive seizure may also result in an obstructed airway, which leads to suffocation. Though it is rare, a seizure may sometimes induce a cardiac arrest and this can result in sudden death.

What you can do: SUDEP is related to seizures. To reduce the risk of death, it is important to control seizures and especially tonic-clonic seizures. You can also reduce the risk of SUDEP by listening to your doctor and taking the prescribed anti-epileptic drug on time. Also, if there is any change in medication, see that it is gradual. Talk to your doctor about controlling seizures at night and use a seizure alarm if you have to. Keep yourself healthy.

A few other complications

Having a seizure at an inconvenient time can be dangerous to yourself as well as others. This is especially true if you drive. If you have a seizure in the middle of traffic, you may cause an accident and injure yourself and others. Such accidents, at times, can be fatal. In fact, many countries have very strict rules regarding issuance of driver’s license to a patient of epilepsy. You may also hurt yourself seriously if you suffer a fall during a seizure. Drowning is also a real possibility if you suffer one while swimming or even in a bathtub.

People with epilepsy can also die from problems that can happen during or after a seizure. One can inhale vomit, and this can be fatal. If you see anybody having a seizure, turn them onto one side immediately. This will allow saliva, vomit or other fluids to drain out of the mouth and not enter the lungs.

WHEN SHOULD YOU CONTACT A DOCTOR?

Consult a doctor immediately if you experience or see somebody experiencing the following symptoms:

• An  epileptic seizure that continues for 5 minutes or more.
• Breathing becomes slow and consciousness doesn’t return even after seizure stops.
• Recurrent seizures with no recovery time in between.
• Temperature is high.
• There is any injury due to seizures.
• A pregnant or diabetic person undergoing seizure          
  
   
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