Regeneration of our cells, brain metabolism and exercise

This is my third week at cross fit exercise training. I wanted to know how my body can regenerate.

  • The human body is an incredible machine.
  • Part of what makes it so impressive (apart from the concept of conciousness and self awareness) is its ability to regenerate itself.
  • Your outer layer of skin, the epidermis (apart from the thicker dermis beneath), replaces itself every 35 days.
  • You are given a new liver every six weeks (a human liver can regenerate itself completely even if as little as 25% remains of it).
  • Your stomach lining replaces itself every 4 days, and the stomach cells that come into contact with digesting food are replaced every 5 minutes.
  • Our entire skeletal structures are regenerated every 3 months.
  • Your entire brain replaces itself every two months.
  • And the entire human body, right down to the last atom, is replaced every 5-7 years.
  • How Your Body Rebuilds Itself In Under 365 Days

We can really influence how this renewal process take place, by the thoughts we have, the food we eat, the life style we adopt, the environment we live in, our relationships, the exercise we take. Most of these things are about the decisions we make.

FACT: Your entire body totally rebuilds itself in less than 2 years – and 98% in less than a year.

Every cell in your body eventually dies and is replaced with new cells. Everyday is a new opportunity to build a new body!

  • Your DNA renews itself every 2 months.
  • Your skin rebuilds itself in 1 month. (especially at night)
  • Your liver rebuilds itself in 6 weeks.
  • The lining in your stomach rebuilds itself in 5 days.
  • Your brain rebuilds itself in 1 year.
  • Your blood rebuilds itself in 4 months.
  • Your body builds a whole new skeleton in 3 months.

(Some research says 2 years some say 10 years*)

There is the saying that your only as old as you feel, so that’s your subjective age.

So if you always feel sick& tired as I hear people say in there frustrating moment, guess what your probably become those thoughts.

There is also the biological age. If you have been a smoker all your life, your lungs will have aged prematurely; or if your life style is very sedentary like most modern cultures,  this will have damaging effects on the body resulting in wear and tear.

There is also the belief among many religious/spiritual followers  that we are in our truest essence an eternal soul which is ageless, timeless and dimensionless.

Of course we have our chronological age which we can not change but we can change the our perception, and decisions about the other ways we behave and age.

Red blood cells live for about four months, while white blood cells live on average more than a year. Skin cells live about two or three weeks.

Colon cells have it rough: They die off after about four days. Sperm cells have a life span of only about three days, while brain cells typically last an entire lifetime (neurons in the cerebral cortex, for example, are not replaced when they die).

Muscle regeneration

Muscle regeneration is the process by which damaged skeletal, smooth or cardiac muscle undergoes biological repair and formation of new muscle in response to death (necrosis) of muscle cells. The success of the regenerative process depends upon the extent of the initial damage and many intrinsic and environmental factors. Key cellular events required for regeneration include inflammation, revascularisation and innervation, in addition to myogenesis where new muscle is formed. In mammals, new muscle formation is generally excellent for skeletal muscle but poor for cardiac muscle; however a greater capacity for regeneration of cardiac muscle is seen in fish and some anurans. These aspects of regeneration are discussed with respect to myogenic stem cells, molecular regulation, ageing and implications for human therapies, with a strong focus on skeletal muscle. Other situations of muscle damage and restoration that do not involve necrosis (e.g. sarcomere disruption and atrophy) are here not considered as regeneration.

Key Concepts:

  • Necrosis is required for muscle regeneration.
  • Inflammation is essential to remove necrotic tissue and initiate myogenesis.
  • New blood vessel formation is required after major injury of muscles.
  • Skeletal muscle has an excellent capacity for regeneration. The major source of myogenic precursor (stem) cells is still considered to be the satellite cell, although other cells lying outside the myofibre may contribute to myogenesis.
  • The source of the myogenic precursor cells (myoblasts) varies between conventional tissue regeneration and epimorphic regeneration (where mature cells dedifferentiate).
  • The microenvironment, including the extracellular matrix, affects all aspects of regeneration, for example, the muscle precursors and their capacity for new muscle formation (and fibrosis impairs myogenesis).
  • Reinnervation is essential for functional recovery of skeletal muscle.
  • Excellent myogenesis can occur in geriatric muscle, although systemic factors essential for regeneration, for example, inflammation and innervation, may be suboptimal.
  • Mammalian heart muscle has a very poor capacity for regeneration and severe damage (e.g. heart attack) results in fibrosis and impaired function.
  • In contrast, the hearts of vertebrates such as salamanders and zebrafish can regenerate; the new heart muscle is derived from the dedifferentiation and proliferation of mature cardiomyocytes. It is hoped that an understanding of mechanisms involved in these situations will present opportunities to induce regeneration of damaged human cardiac muscle.

Adult skeletal muscle is a postmitotic tissue with an enormous capacity to regenerate upon injury. This is accomplished by resident stem cells, named satellite cells, which were identified more than 50 years ago. Since their discovery, many researchers have been concentrating efforts to answer questions about their origin and role in muscle development, the way they contribute to muscle regeneration, and their potential to cell-based therapies. Satellite cells are maintained in a quiescent state and upon requirement are activated, proliferating, and fusing with other cells to form or repair myofibers. In addition, they are able to self-renew and replenish the stem pool. Every phase of satellite cell activity is highly regulated and orchestrated by many molecules and signaling pathways; the elucidation of players and mechanisms involved in satellite cell biology is of extreme importance, being the first step to expose the crucial points that could be modulated to extract the optimal response from these cells in therapeutic strategies. Here, we review the basic aspects about satellite cells biology and briefly discuss recent findings about therapeutic attempts, trying to raise questions about how basic biology could provide a solid scaffold to more successful use of these cells in clinics.

Research is currently ongoing in determining the physiological role of satellite glial cells. Current theories suggest that SGCs have a significant role in controlling the microenvironment of the sympathetic ganglia. This is based on the observation that SGCs almost completely envelop the neuron and can regulate the diffusion of molecules across the cell membrane.[2] It has been previously shown that when fluorescent protein tracers are injected into the cervical ganglion in order to bypass the circulatory system, they are not found on the neuron surface. This suggests that the SGCs can regulate the extracellular space of individual neurons.[22] Some speculate that SGCs in the autonomic ganglia have a similar role to the blood–brain barrier as a functional barrier to large molecules.[23]

SGCs role as a regulator of neuronal microenvironment is further characterized by its electrical properties which are very similar to those of astrocytes.[24] Astrocytes have a well studied and defined role in controlling the microenvironment within the brain, therefore researchers are investigating any homologous role of SGCs within the sympathetic ganglia. An established mode of controlling the microenvironment in sensory ganglia is the uptake of substances by specialized transporters which carry neurotransmitters into cells when coupled with Na+ and Cl.[25] Transporters for glutamate and gamma-Aminobutyric acid (GABA)[26] have been found in SGCs. They appear to be actively engaged in the control of the composition of the extracellular space of the ganglia. The enzyme glutamine synthetase, which catalyzes the conversion of glutamate into glutamine, is found in large amounts in SGCs.[27] Additionally, SGCs contain the glutamate related enzymes glutamate dehydrogenase and pyruvate carboxylase, and thus can supply the neurons not only with glutamine, but also with malate and lactate

 

Molecule[1] Type of Ganglia Method of Detection Comments
Glutamine synthetase Mouse TG IHC Catalyzes the condensation of glutamate and ammonia to form glutamine
GFAP Rat DRG, TG IHC Upregulated by nerve damage
S100 Rat DRG IHC Upregulated by nerve damage
Endothelin ETB receptor Rat, rabbit DRG IHC, autoradiography Blockers of ETs are shown to alleviate pain in animal models
Bradykinin B2 receptor Rat DRG Electrophysiology Involved in the inflammatory process
P2Y receptor Mouse TG Ca2+ imaging, IHC Contributes to nociception
ACh muscarinic receptor Rat DRG IHC, mRNA (ISH) Role not well defined in sensory ganglia
NGF trkA receptor Rat DRG Immuno-EM May play a role in response to neuronal injury
TGFα Rat DRG mRNA (ISH), IHC Stimulates neural proliferation after injury
Erythropoietin receptor Rat DRG IHC
TNF-α Mouse DRG, TG IHC Inflammatory mediator increased by nerve crush, herpes simplex activation
IL-6 Mouse TG IHC Cytokine released during inflammation, increased by UV irradiation
ERK Rat DRG IHC Involved in functions including the regulation of meiosis, and mitosis
JAK2 Rat DRG IHC Signaling protein apart of the type II cytokine receptor family
Somatostatin sst1 receptor Rat DRG IHC Somatostatin inhibits the release of many hormones and other secretory proteins
GABA transporter Rat DRG Autoradiography
Glutamate transporter Rat DRG mRNA (ISH), IHC, Autoradiography Terminates the excitatory neurotransmitter signal by removal (uptake) of glutamate
Guanylate cyclase Rat DRG, TG IHC for cGMP Second messenger that internalizes the message carried by intercellular messengers such as peptide hormones and NO
PGD synthase Chick DRG IHC Known to function as a neuromodulator as well as a trophic factor in the central nervous system

 

Exercise and Lactate

In animals, L-lactate is constantly produced from pyruvate via the enzyme lactate dehydrogenase (LDH) in a process of fermentation during normal metabolism and exercise. It does not increase in concentration until the rate of lactate production exceeds the rate of lactate removal, which is governed by a number of factors, including monocarboxylate transporters, concentration and isoform of LDH, and oxidative capacity of tissues. The concentration of blood lactate is usually 1–2 mmol/L at rest, but can rise to over 20 mmol/L during intense exertion[4] and as high as 25 mmol/L afterward.

During power exercises such as sprinting, when the rate of demand for energy is high, glucose is broken down and oxidized to pyruvate, and lactate is then produced from the pyruvate faster than the body can process it, causing lactate concentrations to rise. The production of lactate is beneficial because it regenerates NAD+ (pyruvate is reduced to lactate while NADH is oxidized to NAD+), which is used up in oxidation of glyceraldehyde 3-phosphate during production of pyruvate from glucose, and this ensures that energy production is maintained and exercise can continue. (During intense exercise, the respiratory chain cannot keep up with the amount of hydrogen atoms that join to form NADH, and cannot regenerate NAD+ quickly enough.)

The resulting lactate can be used in two ways:

Oxidation back to pyruvate by well-oxygenated muscle cells, heart cells, and brain cells Pyruvate is then directly used to fuel the Krebs cycle

Conversion to glucose via gluconeogenesis in the liver and release back into circulation; see Cori cycle[12] If blood glucose concentrations are high, the glucose can be used to build up the liver’s glycogen stores.

However, lactate is continually formed even at rest and during moderate exercise. Some causes of this are metabolism in red blood cells that lack mitochondria, and limitations resulting from the enzyme activity that occurs in muscle fibers having a high glycolytic capacity.

Brain metabolism and exercise

Although glucose is usually assumed to be the main energy source for living tissues, there are some indications that it is lactate, and not glucose, that is preferentially metabolized by neurons in the brain of several mammalian species (the notable ones being mice, rats, and humans).[15][16] According to the lactate-shuttle hypothesis, glial cells are responsible for transforming glucose into lactate, and for providing lactate to the neurons.[17][18] Because of this local metabolic activity of glial cells, the extracellular fluid immediately surrounding neurons strongly differs in composition from the blood or cerebro-spinal fluid, being much richer with lactate, as was found in microdialysis studies.

Some evidence suggests that lactate is important at early stages of development for brain metabolism in prenatal and early postnatal subjects, with lactate at these stages having higher concentrations in body liquids, and being utilized by the brain preferentially over glucose.[15] It was also hypothesized that lactate may exert a strong action over GABAergic networks in the developing brain, making them more inhibitory than it was previously assumed,[19] acting either through better support of metabolites,[15] or alterations in base intracellular pH levels,[20][21] or both.[22]

Studies of brain slices of mice show that beta-hydroxybutyrate, lactate, and pyruvate act as oxidative energy substrates, causing an increase in the NAD(P)H oxidation phase, that glucose was insufficient as an energy carrier during intense synaptic activity and, finally, that lactate can be an efficient energy substrate capable of sustaining and enhancing brain aerobic energy metabolism in vitro.[23] The study “provides novel data on biphasic NAD(P)H fluorescence transients, an important physiological response to neural activation that has been reproduced in many studies and that is believed to originate predominately from activity-induced concentration changes to the cellular NADH pools.

The following will age us: drugs/medications, alcohol, obesity and negative persona.

I will vow not to stop my 30-min cross fit training every morning to keep my cells from growing old.