Wednesday, August 1, 2018

Biology of Aging for Engineer friends




https://www.youtube.com/watch?v=AIzEjm7O11M&feature=youtu.be

The purpose of these series of notes is not to convert into new researchers, only to provide a basic set of ideas to understand some work. Entwined are descriptions of some kingdoms, for some botany, entomology etc. are also needed and thrown in. 99.99% human believe that aging is natural. I don't, and have reasons to believe in life extensions before expected death naturally and even widespread life extension in USA by end of 2020. Any life-extension would dwarf every political dispute ever.

Life is cellular. Less than a cell are viruses. They are perfect salts and reproduce only by invading a host. Routinely, they attack true unicellular beings called bacteria (or archea etc). This attack and destruction can be utilized for narrow spectrum antibiotics against resistant bacteria!

Most important to any life is a cell. A cell for us the main DNA and 0 to 2000 mitochondria. 0 in red blood cells to 2000 in liver cells.  Mitochondria have their own DNA and give rise to own diseases and aging However we ignore aging from it, focusing on main DNA in the nucleus.

The study of aging - gerontology - is a relatively new science that has made incredible progress over the last 30 years. In the past, scientists looked for a single theory that explained aging. There are two main groups of aging theories. The first group states that aging is natural and programmed into the body, while the second group of aging theories says that aging is a result of damage which is accumulated over time. In the end, aging is a complex interaction of genetics, chemistry, physiology, and behavior.
By understanding and describing how we age, researchers have developed several different theories of aging. The two categories are programmed theories and error theories.
  • Programmed Theories assert that the human body is designed to age and there is a certain biological timeline that our bodies follow.
    • Programmed Longevity: Aging is caused by certain genes switching on and off over time.
    • Endocrine Theory: Changes in hormones control aging.
    • Immunological Theory: The immune system is programmed to decline over time, leaving people more susceptible to diseases.
  • Error Theories assert that aging is caused by environmental damage to our body's systems, which accumulates over time.​
    • Wear and Tear: Cells and tissues simply wear out.
    • Rates of Living: The faster an organism uses oxygen, the shorter it lives.
    • Cross-Linking: Cross-linked proteins accumulate and slow down body processes.
    • Free Radicals: Free radicals cause damage to cells that eventually impairs function.
    • Somatic DNA Damage: Genetic mutations cause cells to malfunction.

I have no toleration towards people who subscribe to programmed theories, even if they were to be mostly right because if there is any man-effort in challenging the gods, that belief weakens my morale!


Genetics and Aging

Studies have demonstrated that genetics can play a major role in aging. When researchers adjust the genes in certain mice, yeast cells, and other organisms, they can almost double the lifespan of these creatures. The meaning of these experiments for people is not known, but researchers think that genetics account for up to 35 percent of the variation in aging among people. Some key concepts in genetics and aging include:
  • Longevity Genes: There are specific genes which help a person live longer.
  • Cell Senescence: The process by which cells deteriorate over time.
  • Telomeres: Structures on the end of DNA that eventually are depleted, resulting in cells ceasing to replicate.
  • Stem Cells: These cells can become any type of cell in the body and hold promise to repair damage caused by aging.

Biochemistry

No matter what genes you have inherited, your body is continually undergoing complex biochemical reactions. Some of these reactions cause damage and, ultimately, aging in the body. Studying these complex reactions is helping researchers understand how the body changes as it ages. Important concepts in the biochemistry of aging include:
  • Free Radicals: Unstable oxygen molecules which can damage cells.
  • Protein Cross-Linking: Excess sugars in the bloodstream can cause protein molecules to literally stick together.
  • DNA Repair: For unknown reasons, the systems in the body to repair DNA seem to become less effective in older people.
  • Heat Shock Proteins: These proteins help cells survive stress and are present in fewer numbers in older people.
  • Hormones: The body's hormones change as we age, causing many shifts in organ systems and other functions.

Body Systems

As we age, our body's organs and other systems make changes. These changes alter our susceptibility to various diseases. Researchers are just beginning to understand the processes that cause changes over time in our body systems. Understanding these processes is important because many of the effects of aging are first noticed in our body systems. Here is a brief overview of how body systems age:
  • Heart Aging: The heart muscle thickens with age as a response to the thickening of the arteries. This thicker heart has a lower maximum pumping rate.
  • Immune System Aging: T cells take longer to replenish in older people and their ability to function declines.
  • Arteries and Aging: Arteries usually to stiffen with age, making it more difficult for the heart to pump blood through them.
  • Lung Aging: The maximum capacity of the lungs may decrease as much as 40 percent between ages 20 and 70.
  • Brain Aging: As the brain ages, some of the connections between neurons seem to be reduced or less efficient. This is not yet well understood.
  • Kidney Aging: The kidneys become less efficient at cleaning waste from the body.
  • Bladder Aging: The total capacity of the bladder declines and tissues may atrophy, causing incontinence.
  • Body Fat and Aging: Body fat increases until middle age and then weight typically begins to decrease. The body fat also moves deeper in the body as we age.
  • Muscle Aging: Muscle tone declines about 22 percent by age 70, though exercise can slow this decline.
  • Bone Aging: Starting at age 35, our bones begin to lose density. Walking, running and resistance training can slow this process.
  • Sight and Aging: Starting in the 40s, difficulty seeing close detail may begin.
  • Hearing and Aging: As people age, the ability to hear high frequencies declines.

Behavioral Factors

The good news is that many of these causes of aging can be modified through your behaviors:
  • By eating foods loaded with antioxidants, you can minimize damage caused by free radicals.
  • By exercising, you can limit bone and muscle loss.
  • By keeping your cholesterol low, you can slow the hardening of your arteries and protect your heart.
  • By practicing mental fitness, you can keep your brain sharp.
Lifestyle factors have also been shown to extend life. Rats and mice on a calorie restricted diet (30 percent fewer daily calories) live up to 40 percent longer. Positive thinking has also been shown to extend life in people by up to 7.5 years.

Cell Biology
 https://upload.wikimedia.org/wikipedia/commons/thumb/1/11/Animal_Cell.svg/800px-Animal_Cell.svg.png


Components of a typical animal cell:
1.    Nucleolus
2.    Nucleus
3.    Ribosome (little dots)
4.    Vesicle
6.    Golgi apparatus (or "Golgi body")
7.    Cytoskeleton
9.    Mitochondrion
10.  Vacuole
11.  Cytosol (fluid that contains organelles, comprising the cytoplasm)
12.  Lysosome
13.  Centrosome

Remember that a cell does ALL the things that a life does, all without any magic, spirituality etc, by simple chemistry in my thinking. It is simple if known, very hard if not. Energy is produced by Krebs cycle from food particles, which are carbohydrate, protein or fat through Krebs cycle. This very complicated cycle is idealized as three sub cycles with one tracer molecule. The three tracers are NAD+, ATP and rest of citric acid cycle. NAD which in turn can be synthesized or reused by salvage cycle from the waste products of the previous sub cycle. Synthesis from amino acids is rare. Salvage step is constructed from NMN.  NR makes NMN with the NAMPT filter. Best idealization in my mind is that NMN is one step away while NR is two steps away from NAD+ we need. Direct NAD+ is a bad idea. Every step in biology is about 10% from bio-availability. NAD+ is produced inside mitochondria.
Bioavailability is great engineering block on all bioscience!
Consider CoQ10 which is required by the ATP sub cycle. There are commercial losses before eating. Then there are stomach wall losses, while the molecule enters the blood stream. Then there are cell absorption losses. Finally there are losses to mitochondrial wall. There is always the limiting concentration of the safe carriage of the chemical in blood. So you can at most ingest 1000 mg of CoQ10 is the safe limit on ingesting. Lucky to get 10 mg on all mitochondria!
Science is about determining effects, doctors are really engineers that determine what is needed, then package the needs based on quantity, time and dosage considering the side effects.
Bioavailability is crucial.

It is. So low for glutathione anti-oxidant and melanin reducer (skin whitens). So much that useless in quaff form. Best injected into bloodstream by a drip. That means a medical establishment, common in Korea and opening in India slowly. In both cultures, fairness of skin enhances marriage value! Another is resveratrol. It is the latest failure – great bioscience but poor engineering with catastrophic unpassable bio-availability failures.

What is Coq10?

It is a vitamin like substance which acts as a usefulanti-oxidant in ATP production and thus helps the heart muscle with mitochondria-rich cells. I recommend it at 400 mg per day in divided doses to all above 60, independent of need, solely for Aging disease.

What is called (Arun neologism) a wittig form?

By witting reaction, a form of CoQ10 exists without losses in mitochondrial absorption. Not surpsingly, this form called Mitoq needs only 5mg to equal 500 mg of CoQ10! The general concept is conversion of any molecule to a form that delivers the base molecule without losses at mitochondria.

What more about wittig forms?

There are no wittig forms that came from literature searches except one, the skq1 molecule similar to Mitoq, is loved by Russians and being human tested for anti-aging properties. The wiitigified anti-oxidant is however plant based. Mitoq I suspect has Anti-aging properties not tested properly because it is very pricy ($1-2 per day) (link discounted as sales-pitch). SKQ1 has been approved for human use in Russia! Sold in drug stores!

 

In many ways 2018 is a water-shed year between classic think and new quantum-think. The old dreams will cease to realistic, new dreams will be radically different. I envy those being born. It is all about exponential speed up. An Arab fighter of 1000AD would not have much to learn in 1500 in launch of ships to America. The world changed radically between 1500 and 2000. That difference now happens in 20 years! About others I don’t know, but I still remember CS MTech (1975-1977) at IIT Kanpur and me trying to guess what humans would do with projected IBM mainframe on a chip! There was no internet, Microsoft, Google or Apple or Facebook or mobile phens then! Even more shocking is about encryption in 2000 and today! In 2000AD, I saved for a Gigabyte drive and 128K memory. My latest purchase is 8 GB RAM and 4 TB disks

.
Past the watershed is my phone-sleeve (surrounds any phone for) universal panic button, reminder's to eat medicine - programmable sleeve not software, mobiles that can do lot more using local AI,  5G and killing of TV. Welcome to the 2nd industrial revolution, WHERE DEATH IS RARE AND 1ST GENETIC REVOLUTION WHERE DEBILITATION IS RARE..

Stem cells

A human is formed from union of male and female pluripotent cell repatedly splitting and specializing. Apoptosis message are generated to delete cells produced, The entire process is probabilistic. Biologists classify cells whicch are not in their final specialization into pluripotent 9all can form) to multipotent     Mesenchymal stem cells or MSC. Most early researchers used human PSC obtained from abortions. Nowadays iPS cells (induced) exist which are artificially created.

Mesenchymal stem cells are multipotent stromal cells that can differentiate into a variety of cell types, including osteoblasts (bone cells), chondrocytes(cartilage cells), myocytes (muscle cells) and adipocytes (fat cells which give rise to marrow adipose tissue).

So called iPS are created many ways - one is small chemical/biological modifications of extracted bone marrow from the patient. These can be coaxed into dopamin bearing cells for humans!



No comments:

Post a Comment