Circadian Rhythm

Circadian rhythm clocks regulate thousands, and thousand of genes.

We have an internal clock in the brain. Part of this internal clock that interacts with the external cue of light, and part with the rythem of our eating pattern. The invention of artificial lighting, and the varying work schedules, it has extended peoples eating times to occur much later in the evening, and this can have very negative consequences for health. The distinction between day and night gets lost.

Cell Repair and Regeneration

The regenerative power of tissues, and organs, declines with age. Stem cells provide this regenerative power, and because stem cell numbers decline with age, so does organ function, which means anything that can counter this, is a win. Fasting causes cells to clear away damaged mitochondria, and recycle their defective components for energy, called mitophagy, followed by the generation of new mitochondria, called mitochondrial biogenesis.

Clearing away damaged cells, also means those damaged cells are less likely to become senescent, which is what can happen when too much damage accumulates.

Senescent cells

A senescent cell is technically a living cell, but it is not functioning in a way that is consistent with maintaining the overall health of an organ, in fact quite the opposite.

Senescent cells can accelerate the ageing of nearby cells, and promote tumour growth, by secreting pro-inflammatory molecules, and other factors. Senescent cells are bad news, as we age, they are everywhere, from our livers, to our hearts, to our brains, and they accelerate the ageing process.

Micro-nutrient Triage

My former post-doctoral mentor, Dr. Bruce Ames, proposed that when micronutrients are short supplied, those metabolic processes that are required for short-term survival will get their share of the micronutrient first. Whereas processes that are more concerned with the long-term maintenance, processes involved in mitigating ageing in the long term ultimately get neglected. Bruce calls this evolved strategic rationing of micronutrients the triage theory.

Vitamin D

Some of my work identified that Vitamin D effects Serotonin production. I believe that has very far, far reaching implications. Not just for adults trying to stay healthy and live optimally but also for neurodevelopmental disorders as well.

Approximately 70% of the United States population does not have adequate levels of Vitamin D, which is an amount of 75 nmol/L or greater. That means around 70% of people in the United States are experiencing some dysregulation of their genes due to poor Vitamin D status.

An easy lifestyle change that will have big impact for many people is taking a Vitamin D supplement.

Omega-3.

Approximately 8% of the brains weight is actually Omega-3. Several studies demonstrate that optimizing the intake of Omega 3 has some positive effect cognition or behaviour.

EPA, is a powerful anti-inflammatory fatty acid that has been shown to lower brain inflammation. DHA is a critical component of all cell membranes that makes up 30% of the fatty acids in the brain.

Insulin-like Growth Factor 1

Amino acids, and particularly essential amino acids such as leucine, are more abundant in meat, and are the most potent dietary activators of the IGF-1 pathway. IGF-1 does a lot of stuff. It’s a growth factor that plays a very important role during early growth development, and also is important in promoting and maintaining muscle mass.

IGF-1 acts as a neurotrophic factor, increasing the growth of new brain cells. It prevents brain cells from dying. It’s pretty clear that I actually want some IGF-1 activity.

But there’s also a trade off, as there so often is in biology. IGF-1 is a potent growth factor that allows cells that have been damaged to survive when they otherwise would die. It is important to understand that IGF-1 does not cause damage to the cell, rather it allows damaged cells to live and reproduce so that they can make more copies of the damaged cells. IGF-1 is known as a tumour promoter because it promotes the growth of cancer cells.

I think exercise is the way to tip the balance toward the good. Exercise, whether we’re talking about aerobic or resistance training, has been shown to lower serum IGF-1 levels because exercise causes our muscles to take up IGF-1.

Micro-Nutrients

Omega-3 fatty acids have recently been shown to positively change gene expression in several brain regions and also generally shown to stave off brain ageing.

Micronutrients are about 30 to 40 essential vitamins, minerals, fatty acids and amino acids that we must get from our diet because they are essential for life. That means without them, you die.

Approximately 22% of all the genes that encode for enzymes that require micronutrients as cofactors. That means that the machinery doing work inside your cells actually needs micronutrients to function properly. These are enzymes that are involved in metabolism, neurotransmitter production, repairing damage. Basically, everything that you want to be working optimally needs more than just energy. It also needs micronutrients.

Recommended daily intakes of these vitamins and minerals have been set to ensure we get adequate amounts of them but the RDA isn’t a dependable guide. We do not know how much of these micronutrients we need to stave off ageing as best we can.

Numerous associative studies that have shown in humans that have a high intake of cruciferous vegetables have about a 40% or 50% reduction in multiple types of cancer, ranging from bladder to breast, prostate to lung cancer. But associative studies and prove nothing, although they might point us in the right direction. I spoke earlier about clinical studies on sulforaphane, that seem to confirm this finding.

Dr Rhonda Patrick

Restricted Eating Window - Short-time Fasts

Eating within a 12 hour time period improves sleep, and increases weight loss in most people.

Recent studies suggest that women that previously had breast cancer and ate all their food within an 11 hour time period in changed nothing else in terms of their dietary composition reduced their breast cancer recurrence by 36%.

On the more extreme end , eating within eight hours, is more well known in the fitness world in particular as 16:8 intermittent fasting. Simply maintaining a slightly more conservative time window of 10 hours might show advantages as well, potentially functioning as a lifestyle intervention that may be able to protect people from obesity, metabolic related disease, and more.

You must be in a fasted state to repair damage which is why most repair processes occurring during sleep because that is when most people are in a fasted state. Fasting improves blood sugar, insulin sensitivity, and blood lipids and improves inflammatory markers including C-reactor protein, IL-6 and tumour necrosis factor, TNF Alpha. Fasting improves adiponectin, leptin, and brain-derived neurotrophic factor in humans.

Prolonged Fasting

One of the major benefits of fasting, particularly prolonged fasting, which is around four to five days in humans, is a dramatic increase in the autophagy and apoptosis, followed by a massive boost in stem cell production. Autophagy is a genetic program that is very important, it clears away damaged cells to use for energy, while apoptosis is a genetic program that causes damaged cells to self-destruct, both of these processes prevent damaged cells from becoming cancer cells.

That is not found on a low-carb, high fat diet.

"Modified Atkins Diet, Keto-Adaptation, Ketosis" with Dominic D'Agostino

Found My Fitness: Published on 9 April, 2016

Heat Stress - Saunas

A study published in Joma Internal Medicine in 2015 show that sauna use was associated with longevity. The study recruited over 2,000 middle-aged men in Finland and compared frequency of sauna use with sudden cardiac death, fatal coronary heart disease, fatal cardiovascular disease, and all cause mortality including cancer over the course of 20 years.

The study found that fatal cardiovascular disease was at 27% lower in men who used a sauna two to three times in week and 50% lower for men who use the sauna four to seven times per week compared with men who just used the sauna once a week. In addition to lowering cardiovascular rate of mortality, the study also found that sauna use lowered all-cause mortality full-stop. Using the sauna two or three times per week was associated with a 24% lower all-cause mortality and four to seven times per week, lowered all-cause mortality by 40%.

Inflammation

As a rule of thumb, anything that has the potential to mitigate chronic systemic inflammation, is worth trying to achieve.

A Japanese study was a bit of a surprise to me because several different biomarkers were looked at including blood glucose levels, insulin sensitivity, and even telomere length, None of those predicted successful ageing in each age group up to the super centenarians. Low inflammation was the only predictor of successful ageing in all age groups.

The suppression of inflammation is thought to be one of the most important predictors of successful longevity. That increases in importance with advancing age, and also influences the risk of cancer, and even potentially mental health.

A low-carbohydrate, high-fat diet has also been shown to improve blood glucose and insulin levels and also reduce inflammation.

When we train, as a result of mechanical work being done, we produce metabolic bi-products like reactive oxygen species. We also activate inflammatory cytokines. This is actually necessary to activate genetic pathways that contribute to creating more mitochondria, mitochondrial biogenesis, and also plays a role in muscle building. In fact, it is inflammation that recruits immune cells, such as macrophages, to skeletal muscle in order to produce IGF-1 that helps induce acute muscle repair.

As we can see, inflammation seems to play a pretty important role in the benefits of actual training, and this inflammation, as measured by an inflammatory cytokine known as “IL-6,” actually peaks during training and also right after, but then falls by 50% of it initial peak after the first hour.

Clinical Studies

What gets me really excited are the clinical studies on sulforaphane that show some pretty amazing things. Sulforaphane is one of the micronutrients found in cruciferous vegetables.

For example, men with prostate cancer that were given 60 milligrams of stabilized sulforaphane per day, resulted in slowing the doubling rate of a cancer biomarker known as prostate specific antigen, or PSA, by 86% compared to placebo, which is pretty amazing.

Sulforaphane also activates detoxification enzymes and causes our bodies to excrete carcinogenic compounds.

"Diet-Gene Interactions, Epigenetics, the Vitamin D-Serotonin Link and DNA Damage"

TheIHMC: Published on 3 Feb 2016

Aerobic Exercise

Usually I go for about a three mile run about three times a week. I’m not really an endurance athlete. Whenever I have a big decision to make or something that’s causing me anxiety, these are times I’m especially enthusiastic about going for a run.

Aerobic exercise has been shown to increase the growth of new neurons in the brain by two-fold. Aerobic exercise even starting in mid-life has been shown to almost completely reverse the structural changes that occur in the brain with the ageing. It has been shown that 20 to 40 minutes of aerobic exercise can increase brain-derived neurotrophic factor in healthy men by up to 30%. Even 15 minutes of aerobic exercise can increase some brain-derived neurotrophic factor.

My guest today takes a more nuanced view of things, but she agrees that what you put into your body is foundational to your well-being, and there is no happiness without health. (18 minutes)

Published by: Greatness Clips - Lewis Howes - October, 2020

High intensity Exercise

High intensity training has been shown to improve learning and memory. I do squat jumps for a few minutes at a time.

A highly vigorous exercise makes the demand for energy too high for the mitochondria to cope with. Energy generation at that rate can’t be maintained. In response, after exercise the body produces more mitochondria in your cells. Stress is used to build more capacity in the muscles.

In addition to squat jumps and running, I also lift some weights and do lunges and squats with weights either two to three times per week. It is really important to maintain muscle mass. Starting in middle age, most people lose between .5 to one percent muscle mass per year. We can resist that by training.

One study involving over 300 twins speaks to the importance of legs in particular. Greater strength and power in the legs, was associated with an increased brain volume, and less brain ageing, 10 years later.