Age Regression
Changes in aging is not from loss of function (that something is missing), but an increase of pathogenic damage (diseases of aging emerging in old organisms), requiring a cell-mediated response.
Max Spiers a humanitarian who proposed many abstract theories :
Increasing failure of governments and religion to provide a stable and unifying framework for the organisation of material life
The rise in control of city-states, national monarchies, conditioning of the masses
The magic spell within languages. Neurolinguistics is the study of how the brain's neural systems control language, including how people comprehend, produce, and acquire language. It draws on linguistics, neuroscience, and other disciplines.
The breakup of the feudal structures
Human regeneration for life extension by "a magic molecule" for blood rejuvination
For rejuvination pig internal organs for Deoxyribonucleic acid (DNA) / MicroRNA (miRNA) is a type of RNA molecule that regulates gene expression in cells / Messenger Ribonucleic acid (mRNA) is a single-stranded molecule of RNA that carries the genetic sequence of a gene. Ribosomes read the mRNA to synthesize proteins.
Increasing mitochondria organelles found in the cells (energy for the cell) by blood for sudden outburst of speed, endurance, perception and sharpness
Oxygenation for muscle and cognitive enhancement
Metaphysics ‘the science of things transcending what is physical or natural’, including abstract concepts such as being, knowing, identity, time, and space
Core DNA contains holographic storage of previous ages
COVID conspiracy Dr. Adeel Khan, Circulating Spike Protein Detected in Post–COVID-19 Vaccinated are not allowed to donate placenta / umbilical cord for stem cells.
The Renaissance brought about a series of social, political, and intellectual transformations culminating in Humanism. Researching "adaptive regeneration capability" can exert mastery over nature by diagnosing aging (becoming decrepit / degenerative) symptoms of gerontology, offering dignity of man by health. The effect of humanism, break free from the mental strictures imposed by religious orthodoxy, to inspire free inquiry, criticism, animal studies : breaking down into a range of essential damage repair processes, inspire a new confidence in the possibilities of human thought and creations.
Video : (Max Spiers | planarian regeneration enhanced DNA repair, compare to human germ line by in vitro tissue culture based approach (cell biopsy assay) to gauge for longevity, knock down some of these enzymes, increase somatic mutation rates and show we have accelarated aging (becoming decrepit / degenerative) to identify the pathways how this influences epigenetic status , GDF11's molecular structure is conserved across all vertebrate species e.g. porcine)
Image : Age Reversal Interventions: lifespan-extending effect in elder people :
Age Regression / Cell Reprogramming / Damage Repair / Rejuvenation Therapeutics i.e. IPS,MSC, Plasmapheresis
Age Delaying / Age Slowing / Preventative (Geroprotective Therapy) i.e. Supplements, HBOT
"Two thirds" of the human body is water contained intracellularly (liver, brain, muscles). Next being water in blood plasma. Lastly is water everywhere else (interstitium : connective tissue).
Plasma is the liquid portion of blood. About 55% of the blood is plasma, with the remaining 45% are red blood cells, white blood cells and platelets that are suspended in the plasma. 92% of blood plasma is water, while 8% consists of dissolved substances, mostly proteins. Blood plasma also contains electrolytes, vitamins and nutrients such as glucose and amino acids.
Old blood plasma removal/dilution improved bodily function by resetting signalling pathways to a core gene expression, reduce "inflammatory response, biological noise and DNA damage" whilst boosting stem cell proliferation
Lower Video : Heterochronic parabiosis researched pathogenic / parasitical Old Blood Plasma (OP) to pristine Young Blood Plasma (YP).
Primarily the joining of live mice involved the sharing of organs, which improved the old mouse to the detriment of the young mouse.
Secondarily centrifuging (OP) seperates "blood plasma" that contain suppressive "pro-aging" factors. Transfusion of (OP) to young mice created aging (becoming decrepit / degenerative) symptoms.
Oppositely centrifuging (YP) seperates "blood plasma" that contain rejuvenating, youthful factors, which rejuvinate by proxy when transfused to old mice.
Finally only centrifuging (OP) seperates "blood plasma" that contain suppressive "pro-aging" factors. An equal volume saline replacement of the (OP) reproduced the rejuvenating effect without any need for (YP).
This resulted in the clinical study "Old plasma dilution reduces human biological age"
Age Regression :
Video : (Dr Aubrey de Grey regenerative small molecules, stem cells therapy currently available, Prof Arnold Caplan extending healthspan, preventative therapy before sickness, future damage repair will rejuvenate, Dr Michael D. West exorbitant charges, Dr. Charles Brenner refers to Vadim N. Gladyshev : dividing cells dilute atrophy, future IPS cells targeting Fibroblasts, Core DNA contains holographic storage of previous ages)
Approach of partial reprogramming using nanoparticles in scalable mRNA
Definition by Entropy : Cellular and molecular damage / Epimutations (loss of information at epigenetic levels) causing the pathology of later life mental and physical gait disorders
Ontogenesis : The development of an individual organism or anatomical or behavioural feature from the earliest stage to maturity
Omics : The sum of constituents within a cell containing biomolecules and molecular processes that form and function of cells and tissues
Asymmetric cell division | produces two daughter cells with different cellular fates. This is in contrast to symmetric cell divisions which give rise to daughter cells of equivalent fates
CRISPR | is the exploitation of a bacterial mechanism, that allows bacteriophages to defend themslves against viruses. CRISPR allows us to change the sequence of our genome in a particular cell (gene editing)
Dr. Neil Riordan | MSC's bud off microvesicles which are large enough to contain mitochondria | Anti cancer effects of MSC's, exponential increase in cronic disease in aging (becoming decrepit / degenerative).
Dr Duncan Ross | Exosomes How They Contribute To Our Health.
Dr Aubrey de Grey | MSC Secretome broadly improve cell performance (well being), not focused damage repair rejuvenation
Prof Arnold Caplan | Tissue Engineering MSC's dependant on FBS in media, Embryonic Stem Cells and/or IPSC as Conductive Agent (starting material / catalyst) to stimulate far greater divisions (inductive capacity) to differentiate and expand in vitro cell culture for Tissue Engineering. Collagenases are, enzymes that break down the native collagen that holds animal tissues together.
Dr Michael D. West | Regenerative Medicine and Aging (becoming decrepit / degenerative): Embryonic Progenitor Secretome influence physiology from the basis of cell function at the ionic and molecular level to the integrated behaviour of the whole body and the influence of the external environment.
Dr Ed Park | Mitigating aging (becoming decrepit / degenerative) with exosomes : Epiphany combining supplements with exosomes increasing longevity whilst countries spend trillions inciting wars and unrest.
Yuri Deigin | Epigenetic Rejuvenation by In Vivo Partial Reprogramming: Past, Present, and Future.
Bill Faloon | Stem Cell Regeneration, Young Plasma Infusion, GDF11 Restoration, Senolytics and Senomorphics, Therapeutic Extracellular Vesicles, Mesenchymal Stem Cells, Therapeutic Plasma Exchange, Self-Funded Clinical Research, Clinical Trial Development
Dr Michael D. West | induced tissue regeneration, primordial germ cells. Thomas Kirkwood has a theory called "Disposable Soma", that in nature there is not enough energy for repair and reproduction. An animal devotes its energy to reproduction and leaves repair to the germline cells. During fertilisation the early embryo retains the same epigenetic age signature of its mother until it reaches the "Gastrula Stage" where the embryo's own genes start to take the place of the maternally implanted genes that have been operating it. Gastrulation occurs during week 3 of human development, which the clock resets to zero. The process of gastrulation generates the three primary germ layers which primes the system for organogenesis and is one of the most critical steps of development:
Ectoderm (ectoderm)
Endoderm (digestive tube and the respiratory tube)
Mesoderm (e.g. mesenchymal originates from smooth muscle cells)
The gastrula is an embryo at the stage following the blastula, when it is a hollow cup-shaped structure having three layers of cells. It is not the blastula cells that maintain their perfect fidelity. The return to perfect fidelity is a natural aspect of organisms, it is possible to reset the clock of cell aging (becoming decrepit / degenerative) by cloning technology (Somatic cell transfer, transplanting nuclei from adult cells into oocytes or blastocysts and allowing them to grow and differentiate, producing pluripotent cells) and also by IPS cells. Alternatively approach near pluripotency targetting factors during the "embryonic fetal transition" (~ week 8 from regenerative to fibrotic). Companies in partial reprogramming : YouthBio Therapeutics, Altos Labs, Retro Biosciences, NewLimit, Turn Biotechnologies, Iduna Therapeutics, Shift Bioscience, AgeX Therapeutics, Calico, YouthBio Therapeutics, Gameto, BlueRock Therapeutics (for Embryonic Stem Cell-Derived Midbrain Dopamine Neuron Cell Therapy (MSK-DA01) For Advanced Parkinson's Disease)
Stem cell exhaustion : Stem Cell Recipients
Right Video : (Dr. Neil Riordan's "Magic Juice" secretion (aka Mesenchymal Stem Cell Conditioned Medium), Dan Bilzerian's increased libido, blood flow, stamina, anti inflammatory, sleep, recovery, mental acuity, life extension)
Exosomes method of action is "Unused redundancy of information at the epigenetic level" meaning a more youthful gene expression to reduce the errors of natural messages between different tissues
Consistently reports of Mesenchymal stem cells only offer a transient repair to wound healing
Mesenchymal Stem Cell secretome has a high therapeutic index meaning small to large doses produce few unwanted side effects
Skin, the largest organ in the human body consists of three layers: epidermis, dermis, and hypodermis. The outermost layer of the skin is the epidermis, a thin layer that is tightly packed with epithelial keratinized cells. It is divided into 5 layers namely stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, and stratum basale. The primary achievement of skin barrier function is largely attributed to the stratum corneum. The stratum corneum is the outermost covering of the epidermis, and consists of very tightly packed dead cells known as corneocytes. Stratum corneum acts as formidable physical, environmental, and microbial barriers protecting organisms from external invasion and homeostasis maintenance. Stratum corneum, functions as an effective barrier that restricts the penetration of most drugs, making it challenging for them to cross the skin.
Topical and transdermal applications of Mesenchymal stem cell conditioned medium furnish a promising route for targeted exosome delivery of their regenerative effects directly across the skin for systemic distribution. Using hot water, freshly washed skin feels clean, smooth, and fresh, will open up pores, making skin more pliable. Drugs can penetrate the skin through several modes. The primary modes of skin penetration :
Paracellular (the movement of substances through the space between cells, a passive process that occurs through diffusion)
Transcellular (passing through cells, the movement of molecules or fluids)
Transappendageal (drug delivery through the skin via lipid bilayers, hair follicles, tight junction, sweat glands, and sebaceous glands)
In intercellular or paracellular route, the drug penetrates between the cells of the stratum corneum in contrast to transcellular or intracellular route where the drug crosses directly through the corneocytes of the stratum corneum. The trans-appendageal route is the most relevant for large molecules and particles including nanoparticles as it bypasses the stratum corneum and penetrates via appendages such as hair follicles, sebaceous glands and sweat glands. Penetration of small water soluble molecules can occur through the tight junctions in stratum granulosum. Entry through follicles and lipid bilayer depends on the molecular size and lipophilicity of the molecules.
The dermis, the middle layer of skin, contains many blood vessels that supply nutrients and oxygen to the skin. These blood vessels also help regulate body temperature. Are exosomes hydrophilic or hydrophobic?
Hydrophilic : having a tendency to mix with, dissolve in, or be wetted by water.
Hydrophobic : means "water fearing". These molecules do not dissolve in water, such as fatty acids and cholesterol
Therefore, topical and transdermal applications of Mesenchymal stem cell conditioned medium mimic : Exosome isolation by combining :
Precipitation : falling down in chemical reactions when a solid settles to the bottom of a solution
Size exclusion chromatography (SEC) : is a laboratory technique that separates molecules in a solution based on their size. It's also known as gel filtration chromatography or gel permeation chromatography.
Right Video : (Dr Ed Park : Secretions of young MSC's Extracellular vesicles (EVs) dissipate (to separate and go in different directions) by diffusion (diffused or dispersed)
Paracrine Signaling : releasing proteins, a type of intercellular communication in which a cell produces a signal, triggering a signaling cascade to induce changes in nearby cells, altering the behaviour of those cells to survive, divide, differentiate or die
Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material)
Age Delaying : Fisetin
Senolytics
Upper Image : Strawberries contain 160 μg/g of Fisetin
Research show Strawberries contain Fisetin protein, a powerful Senolytic. Fisetin, a dietary antioxidant for health promotion and gives neuroprotection. Fisetin possesses antiproliferative properties against several cancers: Lung cancer, colon cancer, prostate cancer, pancreatic cancer, melanoma. Research shows that Fisetin counteracts the stem cells therapy so is not taken in conjunction
Strawberries are high in flavonoids, which are secondary metabolites that have antioxidant and anti-inflammatory properties
Deregulated Nutrient Sensing : Calcium Alpha-Ketoglutarate (Ca α‐KG)
Ca α‐KG is not available in food sources so must be delivered exogenously (having an external cause or origin)
Generally Recognised as Safe (GRAS)
Stimulate production of reactive oxygen species (ROS) in mitochondria. Reactive oxygen species (ROS) play a role in cellular processes like cell growth, apoptosis, and migration. However, excessive ROS production can damage DNA, proteins, and the cell plasma's lipid bilayer.
Caloric restriction mimetics often function via similar pathways to caloric restriction, such as the mTOR signaling cascade, a molecular mechanisms of Ca α‐KG (mTOR inhibitor) can imitate a state of caloric restriction.
Ca α‐KG | interview with Tom Weldon effects on epigenetic age & health |
17-α estradiol | male lifespan extension of median increase in survival of 19%
Ca α‐KG Increases
Ca α‐KG supplement increases both lifespan and healthspan
DNA methylation age decreased by 8.31 years (10% life extension)
Ca α‐KG increases healthspan of older aged by 40%(activities of daily living)
Revitalising cellular energy to restore vitality (metabolic function)
Helping to identify and fight pathogens
Improved Mental Acuity
Improves Muscle Repair (Protein synthesis)
Increases Adult stem cell function
Improves Metabolic flexibility (ability to adapt to conditional changes in metabolic demand) e.g Significantly increasing circulating levels of insulin
Tricarboxylic acid (TCA) cycle involved in central metabolism
Tricarboxylic acid (TCA) cycle involved in Amino Acid catabolic processes
Effects Oxidative Stress / Enhanced Respiration (the capacity for the organism to adapt fuel oxidation to fuel availability)
Enhances Cellular Respiration
Activates HIF-1α, which is a low oxygen response that has been shown to affect aging (becoming decrepit / degenerative)
Red Blood Cells readily take up AKG driving Glutathione production (better exercise endurance)
Reducing 30+ signs of age-related frailty (morbidity), and fertility decline
Reducing protein breakdown, harmful oxygen molecules within cells and prevents damage to tissues
Reduced mTOR signaling and attenuates Wnt signaling, suppresses ATP synthase
Detoxifies Hydrogen Peroxide (H202) and Ammonia (NG4+) into Glutamate, which becomes Urine
Eight Roots of Aging : Degenerative, becoming decrepit of illness marked by gradual deterioration of organs and cells along with loss of function
1. Junk - Inside Cells
Waste Within Cells Transgenic microbial hydrolases / gene therapy
For metabolic reactions to synthesise the proteins or hormones required for life sustenance, our cells produce and accrue waste products inside them. However, as people get older, their “cell waste” disposal capabilities deteriorate, triggering molecular debris and protein accumulation in cells. The resulting debris and protein aggregations propagate tissue breakdown and organ dysfunction, leading to age-related diseases where failing lysosomes (from a by-product of vitamin A) causing macular degeneration, metabolic disorders, cardiovascular ailments / atherosclerosis (from a by-product of cholesterol), and eventual death.
2. Junk - Outside Cells
Waste Between Cells Phagocytosis by immune system
Proteins and other cellular debris can accumulate outside and between cells begetting their pile up. Resulting debris and protein conglomerations impede cellular connections and their communication with other surrounding cells, triggering cell death, tissue and organ dysfunction, and eventually diseases that provoke death.
3. and 4. Cells - Too Few / Many
Stem Cell Loss and Higher Levels of Senescent Cells Stem Cells and Suicide genes, immune stimulation
As we get older, aged, non-proliferating cells called senescent cells that release a milieu of inflammatory substances build up in our bodies and cause age-related inflammation (inflammaging). Aubrey de Grey proposes that during our lifetime, the ratio of healthy stem cells to senescent cells diminishes, resulting in an imbalance that constitutes a major origin of aging (becoming decrepit / degenerative).
5. and 6. Mutations - Chromosomes / Mitochondria
Genetic Mutations Telomerase/ALT gene deletion plus periodic stem cell reseeding and Allotopic expression of 13 proteins
Two types of mutations that can impart aging (becoming decrepit / degenerative), disease, and ultimately, death include those to DNA that codes for proteins used throughout the body (nuclear mutations) and others for the cell’s power-generating structure — the mitochondria. Nuclear mutations can cause diseases like cancer and diabetes, while mitochondrial mutations limit the cell’s capacity to produce energy and result in mitochondrial diseases that lead to death.
7. Protein Crosslinks
Bonds and Interconnections Between Proteins Age breaking molecules/enzymes
As the final aging (becoming decrepit / degenerative) cause, de Grey proposes that bonds and links between cells that allow them to communicate and form cohesive tissues over-accumulate during aging (becoming decrepit / degenerative). The multiplication of bonds connecting cells then causes a detrimental loss of tissue elasticity and can facilitate diseases like arteriosclerosis — the hardening of blood vessel walls.
8. Persistent Viruses
Persistent continually recurring Viruses accumulating in aging (becoming decrepit / degenerative cells that is not successfully cleared Antiviral medications can treat single outbreaks or Shingles vaccine
Cytomegalovirus, Herpes simplex virus (HSV), known as herpes, is a common infection that can cause painful fluid-filled blisters on your skin or ulcers. Shingles (herpes zoster) / Chickenpox (varicella zoster). Pathological viruses are alien to the human body, which need to be cleared and removed. Shingles vaccine could reduce Alzheimers disease.
Image : Age Reversal Interventions: lifespan-extending effect in elder people :
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