Sea anemones (reproduce only by cell division, called mitosis).

  

Hydra (they have both a sexual (meiosis) and an asexual life, so can compare the two).

 

Conclusion; there is no mandate in biology to age

What was Mom’s age when you were born?
How could you start out at 0 years old when she gave you cells she had lived with for decades?

 

What was your grand-mom’s age when your mom was born?

You now see that you are descendant from a long line of non-aging germline cells.

Conclusion; there is no mandate in biology for a sexual animal’s cells to age

a. The genome (DNA) of somatic cells is still intact in older humans (Sinclair D 2018) and the genetic heritability (h²) of human longevity is less than 7% (Ruby JG 2018), but the epigenome (methylation of DNA) of somatic cells in humans deteriorates (exponentially: Gompertz B 1825) with age.

Full healthy animals can be made from a single older somatic cell.

b. Somatic cells from sexual animals do not age until after puberty

 

In flat worms (C. elegans) germline cells send “an order” to triple methylate genes in somatic cells to turn off their repair systems, which saves organismic energy, but which also starts aging (Labbadia J 2015 and 2017). In mammals the longer the time to puberty (sexual maturity) the longer the life span on average of the animal.

The writer postulates a similar occurrence in humans at the time of puberty that start aging in humans. The ultimate cure then for aging will occur when these age-causing-methyl-changes at pre /post puberty are differentially determined and reversed with In Vivo Crisper/Cas9-mediated trans-epigenetic modulation (Liao HK 2017)

Conclusion; there is no mandate in biology for somatic cells of sexual animals to age.

a) During times of calorie restriction, the time is not right for having babies, so sexuality is turned off and repair is turned on, so you do not age, when calories come back and babies are born you then have extra years to take care of the babies born with the new calories.

 

b) There is a 3 X variance of the rate of aging in humans (DW Belsky 2015) some human individuals are aging at a rate three times faster than other human individuals.

c) Somatic cell division prior to full DNA repair locks in DNA damage. This is a slight complexity to our story since this locked in DNA damage cannot be repaired and if in certain locations can be a cause of cancer. Repair systems try to hold off cell division for this biological reason.

Conclusion; the repair mechanisms of somatic cells can be turned on to stop their aging.

Experiments in 2000 show there is no life extension with calorie restriction without sirtuin enzymes, thus sirtuin enzymes are necessary for repair and age reversal.

Conclusion; the general mechanism of somatic cell repair has been found.

  

The main aging theories of the past were never proved wrong, but they individually never proved sufficient to explain aging either. The calorie restriction theory now shown to be sirtuin dependent, the free radical theory is now shown to be about reduction/oxidation balance and the methylation theory now described as epigenetics all are important in understanding aging as are other theories. Taken together these theories give an understanding of the decision switch that turns cellular repair on and off.

    

Conclusion; biological regulation sometimes needs to see patterns to make effective decisions.

a) Energy depletion (sirtuins need energy depletion to turn on and stay on)

 
High NAD+ ( a co-substrate for sirtuin enzymes, no NAD+, then no sirtuin activity)
High cAMP (caffeine in coffee make this stay around) (cAMP accelerates sirtuin activity)

Studies showed NAD+ levels went down by half in older human adults (and other animals). The NAD+ theory of aging came from this. The thought was that if you increase NAD+ (just by itself) it would turn on Sirtuins and give individuals the calorie restriction effect of reversing aging all by itself. As you will see, several other things need to happen to keep Sirtuins turned on and kept on to get the age reversal effect of calorie restriction that has been seen in all animals it has been used with. It is possible, though, to reverse human age with several small additions to this singular theory.

b) Reduction/oxidation (REDOX) balance (sirtuins need reduction to turn on and stay on)

i) CD-38 is turned off with reduction, so it does not degrade NAD+ and NMN

ii) Thiol (a sulfur that senses REDOX balance) reduction is needed to keep sirtuins active

iii) Reduction is needed to keep the methylation pathway going to SAM, not glutathione

c) Methylation (sirtuins need methylation to turn on and stay on)

i) SAM availability (it provides the methyl of methylation)

ii) Nicotinamide’s methylation is needed to stop nicotinamide from its “feedback loop” turning off of sirtuins enzymes

iii) Epigenetics (correct methylation of DNA allows correct expression of genes)

Conclusions; changes “seen” in biological patterns can lead to biological choices by organisms.

Initial study results: 12 males from 46 to 66 years of age on Egaceutical’s triple therapy EGA® were shown (in addition to many other aspects of age reversal) to reduce their interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) and when compared to results from the Y. Arai 2015 study this indicated they had reduced their biological age, increased their predicted life span, and they had elongated their physical and mental health-span by reducing/reversing their progression towards the “diseases of aging”.

Conclusions; the initial study’s result data supports the theory that human sirtuin enzymes can be turned on and kept on with EGA® therapy long enough to cause significant age reversal in humans.

a) Exercise (oxidative preconditioning)

i) Quality

Endurance

1 hour of running adds 7 hours of life

Strength (each muscle needs its own attention, use them or loose them)

2 times per week good, 1 time per week not enough

Intensity of workout

Light sweat (good)

Are unable to carry on a conversation (better)

ii) Quantity

Hours /week

5 strenuous hours/week (gets most of exercise benefit)

Some benefit was seen from even short intense spurts of exercise

b) Sleep (a time for repair)

i) Quality

 

Problems with first non-REM slow-wave sleep of night when age

ii) Quantity

4 REMs (6.5 hours) or 5 REMs (8 hours) per night usually required

c) Diet (a more varied diet is healthier, also has a correlation to the microbiome in gut)

i) Limiting the eating time period during the day

It appears that you cannot repair your cells when you are digesting your food, your body chooses to do one or the other, so not eating allows your body to repair your cells. Fasting is difficult, so better to have a daily routine of not eating at all. Center eating on 1 pm to 2 pm. 12 hours is better than 24 hours of eating this has been shown in mice, 8 hours of eating is probably better than 12, and 4 better than 8?

ii) Quantity of diet

Correct amounts of nutrients are needed. Too little or too much of any nutrient is bad. Example water: too much or too little can kill you. Fat (leads to energy via the TCA cycle) satiates better than sugar (glucose leads to energy via glycolysis, fructose has other properties), excess sugar is bad in regards to aging.

iii) Quality of diet

The fat (TCA) pathway is better to have turned on than the sugar (glycolysis) pathway to get energy for cellular repair.

But the brain does need some glucose (sugar) from the glycolysis pathway for its energy.

Protein is needed.

Dietary restriction with a diet below 10% protein has in experiments had health span and life span benefits due to the lower amount of amino acids effect on the mTOR cellular pathway. It does not matter if the protein is from plants or animals. Blue zone individuals that live healthier lives eat around 8 or 9% protein in their diets. Average Americans eat between 10% and 35 % protein in their diets. It may be that sialic acid, which humans now cannot synthesize, from animal meats increase inflammation leading to disease such as vascular disease.

Cooking often helps to get the nutrients out of foods and this has allowed humans energy benefits to power our brains that are 3 times larger than bonobos’ and use 25% of our energy. We also gave up muscle strength for our larger brains. Our muscles are 2/3 the strength of bonobo’s muscles in strength, showing energy tradeoffs in evolution.

 

Things that once lived are better than man-made nutritional constructs.

Things that have not deteriorated since death are better nutrients.

Younger plants/animals are better than older in regards to nutrients.

Although fruits are made by plants to be eaten,

the plant itself, if not engineered by humans, will have toxins to keep animals from eating it.

 

Pesticides and preservatives that are meant to kill microorganisms to protect the food supply and the food supply’s shelf life also affect your bacteria and other life forms in your microbiome in your gut. This is probably deleterious to your health and longevity.

 

The types of microorganisms in your microbiome have been shown to be important to the rate at which you age. You need the right mix of micro-organisms in your gut to keep you healthy. It is extremely difficult to change them and their ratios to each other inside of you.

To some extent these microorganisms are telling your brain what you should eat for their benefit, not necessarily yours. And what you eat supports the type of micro-organisms sending the signals to your brain. So there is a loop that is hard to change.

d) Daily cycles and your biological clock

NAD+ peaks twice a day and troughs twice a day; each 12 hours apart. Ex: 8 am and 8 pm NAD+ peaks (may vary with a morning person or an evening person). About 2/3 of cell activity is correlated with the swings of your two daily clock cycles. Greater swing (peak height vs. trough depth) of two cycles per day is better for health.

Human mother’s milk has NMN and NAD+ and its quantity is dependent on lactation time, so mom’s milk’s composition is dependent on her biological clock and her baby’s.

e) Emotions (happiness is ½ genetic and ½ dependent on your life’s present compared to your life’s last 3 to 6 months, so it is all about you and your subconscious brain’s analysis of your life).

Energy is more likely to be allocated (for repair) if the prediction for the future is good (i.e. you are happy).

Past exercise may be a surrogate for a prediction of a good future to the subconscious leading to mental happiness.

i) Positive (estimation that the present is better than the past 3 to 6-month average). Shown to elongate life.

ii ) Negative (estimation that the present is worse than the past 3 to 6-month average). Shown to shorten life.

f) Other means of Hormesis (a very small negative prepares for a great big negative)

i) Heat Shock (2 mins of 102 F denatures proteins and turns on heat shock proteins)

This is a tradeoff of the negative effects of the heat that unravels your proteins, thus causing harm, but this turns on beneficial chaperone systems and repair. So to maximize benefit only do the bad thing (heat) for as brief a time as needed to turn on repair. Also, protect germ line cells (testicles) since they already have repair on.

ii) Cold Shock (2 min of 35-38 F denatures protein and turns on heat shock proteins).

This is the exact same thing as heat only here cold denatures your proteins. The benefit does not come from the cold (or heat) but when your temperature comes back to normal. Water is better to use than air since it conducts temperature better.

iii) A Short Stress

These small-short-time-frame stressors allow a person to better deal with larger life stresses when they appear. Humans are not made well for long stresses.

iv) Vaccines

Hopefully in the future we will have vaccines to viruses that accelerate aging
Cytomegalovirus (ties up the immune system in old age, if have CMV)
Human Herpes virus 1 & 6 (may trigger Alzheimer’s disease to start)

g) Besides the main causes of inflammation which include active pathogens, recent trauma and flare-ups from endogenous viruses, other possible, probably lesser, environmental causes of increased inflammation (research on these is not robust) in our modern world include: chemicals in cosmetics, lotions, perfumes, fragrances, deodorants, dry cleaned clothes, shampoo, conditioner, nail polish, as well as leaked BPA (and even its replacements) used in plastic bottles and the oxidation caused by high levels of radio frequency (RF) waves from cell phones held too close to the body (this RF effect drops off with the square of distance from body) and even breathing too much dust from living too near a major busy road.

Conclusions; Scientific theories remain if they continue to be supported by all (unbiased) data.

a)  In the 2015 Y. Arai study, aging, the diseases of aging and death starts when, but not before, the predictive variables IL-6 and TNF-α increase, thus this study predicts that aging, the disease of aging, and death due to aging will not happen if IL-6 and TNF-α levels are not allowed to rise past the low levels of youth.

b) Death by injury only (car crash is #1) leads to 9,000 to 50,000-year life expectancy

Conclusions; new data leads to new theories and the need to rethink previous unproven assumptions