Marilyn's Column | March/2017
Topic: Fasting - How it helps our Metabolic Repair System.
Today's Question: Is Fasting really Important and what does it Do?
Answer: Repair and Maintenance. The human organism has evolved DNA repair and DNA protection against oxidation and regeneration using the body's own stem cells. It has been shown that fasting and exercise build new neurons in the CNS and the Brain. This regeneration response represents one of the most potent examples of comprehensive cellular reprogramming and appears to be functioning in virtually all organisms. (1,2)
Fasting | the Normal State for Humans
Fasting is the Normal State for Humans: in the biological world, most organisms exist in a fasting state and Eating is a Stress State. (Note 1) During starvation periods and lack of carbohydrate sources (seasonal), the formation of ketone bodies increases dramatically. Prolonged low levels of insulin result in both increased fatty acid release from adipose tissue, and increased amounts of the enzymes required to synthesize and utilize ketone bodies. Ketone fuel is more efficient and has less waste by products. (3) Modern elite runners are now proving that Ketogenesis Energy provides 50-80 Kcal vs 2-3 Kcal of glucose energy. This makes the human animal an excellent long distance runner.
When you are asleep, you are fasting. Most animals alternate periods of feeding with periods of fasting often coinciding with sleep. Fasting and Time-Restricted Feeding, TRF, allows mammals to enter alternative metabolic phases, which rely less on glucose and more on ketone body sources. Both intermittent (IF) and periodic fasting result in benefits ranging from the prevention to the enhanced treatment of diseases.
Immune system defects are at the center of aging and a range of diseases. Here, we show that prolonged fasting reduces circulating IGF-1 levels and PKA activity in various cell populations, leading to signal transduction changes in long-term hematopoietic stem cells (LT-HSCs) and niche cells that promote stress resistance, self-renewal, and lineage-balanced regeneration. Multiple cycles of fasting abated the immunosuppression and mortality caused by chemotherapy and reversed age-dependent myeloid-bias in mice, in agreement with preliminary data on the protection of lymphocytes from chemotoxicity in fasting patients. The proregenerative effects of fasting on stem cells were recapitulated by deficiencies in either IGF-1 or PKA and blunted by exogenous IGF-1. These findings link the reduced levels of IGF-1 caused by fasting to PKA signaling and establish their crucial role in regulating hematopoietic stem cell protection, self-renewal, and regeneration. (5)
- Prolonged fasting downregulates a IGF-1/PKA pathway in stem cells
- Prolong fasting protects hematopoietic cells from chemotoxicity
- Prolonged fasting cycles promote HSC self-renewal to reverse immunosuppression
- Inhibition of IGF-1 or PKA signaling mimics the effects of prolonged fasting
Circadian Rhythm, is the daily day/night cycle which regulates our metabolism. The master circadian oscillator in the hypothalamic suprachiasmatic nucleus, Hippocampus, is bound to the day/night cycle by retinal photoreceptors. (3) (Note: 1) Regulation of the circadian timing system by light and food. Under normal conditions of ad libitum (as desired) food, light synchronizes the master clock, the suprachiasmatic nuclei (SCN), which then synchronizes peripheral clocks via neuronal and endocrine pathways, ... (4)
The circadian rhythm turns on and off genes to regulate DNA repair, and it is now shown that DNA repair occurs during fasting periods, i.e. "Sleep and Time-Restricted Feeding". (Video, 6,7,8) Sleep is regulated by two body systems: Sleep/Wake homeostasis and the Circadian biological clock . Completely different genes are active during these cycles. (9,10,11,12)
Dr. Patrick and Dr. Panda discuss our current state of knowledge about the Circadian Rhythm and how it turns on and off genes while we are awake and asleep in the following:
Time-Restricted Feeding and Its Effects on Obesity, Muscle Mass & Heart Health | June/2016.
Dr. Panda discusses his research results ...
Satchidananda Panda - Watching Your Diet: One Click at a Time | May/2016.
He presents the actual facts of our eating habits. Collected from A New Study
App Tool for Circadian Rhythm: myCircadianClock.org.
Restricted Feeding | Sleep and Fasting
DNA repair is an essential cellular function, (20) which, by removing DNA damaged cells before they mutate, contributes
crucially to the prevention of cancer. For best recovery from stress our body needs a Rest Time.
This means sleep and fasting, as the current knowledge indicate that our Circadian Rhythm controls DNA repair. The genes that control DNA repair are turned on
only when our body is fasting. This simply means that our sleep/fasting cycle is one function -
Restricted Feeding. Studies show that
Restricted Feeding is very beneficial to living organisms.
(Note 2, 3, and 4)
A minimum of 12 hours for a healthy recovery, is required for the
Restricted Feeding cycle. To create Strength and Endurance this cycle should be 15 hours.
Time-Restricted Feeding and Its Effects on Obesity, Muscle Mass & Heart Health | June/2016.
(Video) Limiting eating to 8-9 hours has many benefits i.e. active hours. DNA repair happens during fasting, this is new understanding of fasting physiology and our primordial rhythms. (21,22)
myCircadianClock.org app that helps you understand your body's rhythms while contributing to research. (23)
- There is a metabolic master clock and it resets and turns on and off genes throughout the day. There are internal clocks that regulate organ clocks and body chemistry by regulating 3-6000 gene expressions on a daily cycle. This is approximately 25% of our genes on a clock. Bad diet effects these clocks and time restricted feeding resets these clocks. (24,25,26) (Note 3)
- Restricting feeding is important to DNA repair, and allows the body's immune response to rebuild and repair bodily tissues. Therefore, we are biologically set to an eating cycle that depends on the sun. And for best
results we should at a minimum fast for 12 hours. If we can go 15 hours even better, however, that only leaves a 9 hour time slot to eat. 8-5 then fast, which is hard to do but 8-8, or 7-7 is manageable. Water only otherwise.
Satchidananda Panda - Watching Your Diet: One Click at a Time | May/2016
presents the actual facts of our eating habits. Collected from A New Study
AppTool for Circadian Rhythm: myCircadianClock.org.
- Fasting has been practiced for millennia, but, only recently, studies have shed light on its role in adaptive cellular responses that reduce oxidative damage and inflammation, optimize energy metabolism, and bolster
cellular protection. In lower eukaryotes, chronic fasting extends longevity, in part, by reprogramming metabolic and stress resistance pathways. Human trials are about start, but in animals intermittent or periodic
fasting protects against diabetes, cancers, heart disease, and neurodegeneration, while in humans it helps reduce obesity, hypertension, asthma, and rheumatoid arthritis.
Thus, fasting has the potential to delay aging and help prevent and treat diseases while minimizing the side effects caused by chronic dietary interventions.
Additionally, fasting state to feeding state triggers stem cell regeneration and growth, and has been shown to generate new brain cells. (25) The formation, maintenance and reorganization of synapses are critical for brain development and the responses of neuronal circuits to environmental challenges. (26)
- A circadian rhythm is a roughly 24 hour cycle in the physiological processes of living beings, including plants, animals, fungi and cyanobacteria. Circadian rhythms are important in determining the sleeping and feeding patterns of all animals, including human beings. The study of circadian rhythms is called chronobiology.
- Decreases in fat mass in animals fed an ... Obesogenic Diet.
- Increases in lean muscle mass when on a normal diet.
- Improvements in glucose tolerance and insulin sensitivity.
- Reduction in inflammation, improvements in lipid profile, and favorable changes in gene expression-epigenetics. (26)
- Increases in mitochondrial volume, especially in the liver and brown fat, and an increased production of ketone bodies. (27)
- Protection from mild age related hepatic steatosis. In the obese this effect was especially effective, and a 53% reduction in triglyceride accumulation was seen.
- Further restriction showed an enhancement of endurance in the context of aerobic exercise.
Cellis a perfect lean mean machine, and we replace all of our cells regularly. Our bodies are doing this every second, plus DNA repair, and immune responses. The cell has evolved to grow, reproduce, and repair itself. 2 billion years to achieve this, then they started organizing ...
The Human - Two Biological Organisms in One.
Our favorite youTube presentations on the cell are: TED TALK: The secret, social lives of bacteria, Dr. Bonnie Bassler | april/09 (28) Chemical Conversations: How Bacteria Talk to Each Other , Dr. Bonnie Bassler | august/10 (29)
Genes are activated, mitochondrial biogenesis is turned on and with it comes the body's own antioxidant response which is used by our immune system.
This is known as Hormesis (20) a beneficial response to stresses (improved health, stress tolerance, growth or longevity).
There is lactate generation which modulates the glycolytic system, (31) molecular mediators used by the cells and all oxygen dependent energy production cycles,
(ex. obesity and insulin resistance (32)) the inflammation response is the body's diagnostic and repair response to stress, whether it is
Exerciseor the complex modern