Age Regression
| Aging Blood Plasma Proteome | Age Regression | Stem Cell Exhaustion |
| Cellular Senescence | Deregulated Nutrient Sensing | 8 roots of ageing |
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Theorists, Historians Max Spiers a humanitarian who proposed many abstract theories :
 Elizabeth Bathory wiki | audio clip | 21.00 blood rejuvenating, 22.10 lambs placenta, 22.20 blood as face cream Hoak | not spelt or pronounced with a ending "X" suffix | "Hoak" Meaning (rare word in specific regional dialect or subculture): "To search" ; Often used to describe an unseen force that acts with a strongly felt, yet indescribable power in Energy / Dimensions / Genes / Evolution / Emotions / Intuition / Empathically / Strong Nuclear Force 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. Upper Video : The greatest bioengineer is evolution. e.g. compared 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
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Plasmapheresis : 
Image : lifespan-extending effect in elder people : Age Reversal Interventions
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 Susan Main, Nurse Clinician | What is Plasmapheresis A dielectric study | on human blood and plasma Louis Hawthorne | Apheresis treating aging (becoming decrepit / degenerative) , leukemia and myasthenia gravis Louis Hawthorne | Apheresis treating aging (becoming decrepit / degenerative) removing aging factors Young plasma has special proteins that rejuvenate tissues | Reverse Aging (becoming decrepit / degenerative) Albumin conspiracy Donating Plasma just as effective as TPE Upper Video : Heterochronic parabiosis
OP : Old Plasma, pathogenic blood / parasitical YP : Young Plasma, pristine blood / immature 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"
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Age Regression : 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 Definition by Atrophy : A decrease in size of an organ / gland caused by disease or disuse e.g. Thymus Stem Cells : Liposomal, Lysosome, Spatial Transcriptomics, Oligonucleotide Ontogenesis : The development of an individual organism or anatomical or behavioural feature from the earliest stage to maturity Plasticity : an organism's ability to change its phenotype (physical or behavioral traits) in response to environmental changes without altering its genotype. Plasticity can manifest at the cellular, developmental, and behavioral levels and is crucial for adaptation to fluctuating conditions and can even play a role in long-term evolutionary processes. Supracellular : a level of organisation or scale that is beyond or above the individual cell, encompassing the behavior of groups of cells as a cohesive unit or the mechanical and structural connections between them. e.g. collective cell migration Omics : The sum of constituents within a cell containing biomolecules and molecular processes that form and function of cells and tissues Upper 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 entropy, future IPS cells targeting Fibroblasts, Core DNA contains holographic storage of previous ages Rejuvenation with Young Stem Cell Exosomes Decoding the Science | Dr Paul Robbins Interview 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 Dedifferentiation | is a transient (short-lived) process by which cells become less specialised and return to an earlier cell state within the same lineage 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 Duncan Ross | For rejuvenation: Middle age to start using Exosomes is when largely healthy . elderly have risk being immunocompromised. 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 Dr Aubrey de Grey | repairing 7 types of damage 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:
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 : Altos Labs, Retro Biosciences, NewLimit, Turn Biotechnologies, Iduna Therapeutics, Shift Bioscience, AgeX Therapeutics, Calico, YouthBio Therapeutics, Gameto, BlueRock Therapeutics, Rejuvenate Bio (for Embryonic Stem Cell-Derived Midbrain Dopamine Neuron Cell Therapy (MSK-DA01) For Advanced Parkinson's Disease)
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reactivation of endocrine system : (hypothalamus, pituitary gland) increasing libido / angerRotating Animation : 4 types of glial cells are: (1) microglia, (2) astrocytes, (3) oligodendrocytes, and (4) their progenitors NG2-glia Dongsheng Cai's research showed inflammation, created from Glial cells, are a driving factor in the hypothalamus which causes aging (becoming decrepit / degenerative) through out the whole body. |
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Stem cell exhaustion : Stem Cell Recipients
Upper 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 for skin treatment" article explains for Mesenchymal Stem Cell Conditioned Medium :The skin helps maintain homeostasis (metabolic equilibrium that operate via the autonomic nervous system to offset disrupting changes). 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. Vasodilation (widens blood vessels) cools you down by increasing blood flow to the skin, which helps the body lose heat. This increased blood flow brings more heat to the skin's surface, where it can be lost through radiation and evaporation. Vasodilation is a response to being too hot. Mesenchymal stem cell conditioned medium can be absorbed through the skin into blood capillaries (tiny blood vessels that connect arteries and veins in the skin). Drugs can penetrate the skin through several modes. The primary modes of skin penetration :
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. The hypodermis is located directly beneath the dermis, which contains fatty layer of skin, containing fat and lipids. Are exosomes hydrophilic / hydrophobic / lipophilic?
Biologically active compounds can be found inside exosomes or associated to their surface molecules. Because of their amphiphilic characteristics they can carry both hydrophobic and hydrophilic molecules.Therefore, topical and transdermal applications of Mesenchymal stem cell conditioned medium mimic : Exosome isolation by combining :
Upper 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)
Mesenchymal Stem Cell Secretome can both produce free radicals and counteract them through various antioxidant mechanisms, including direct scavenging, promoting endogenous antioxidant defenses, and modulating cellular environments. Strategies to protect MSCs from free radicals, such as astaxanthin, are being explored to preserve their quality and therapeutic effectiveness. |
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Age Delaying : Fisetin (Cellular Senescence) / Astaxanthin 
SenolyticsUpper Image : Strawberries contain 160 μg/g of Fisetin
Carotenoids
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Deregulated Nutrient Sensing : Calcium Alpha-Ketoglutarate (Ca α‐KG) 
Ca α‐KG Increases
DNA methylation age decreased by 8.31 years (10% life extension)
Ca α‐KG Decreases
Ageing Research on Ca α‐KG reduces Epigenetic Age in Humans |
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Eight Roots of Aging (7 + 1 Categories) : Degenerative, becoming decrepit of illness marked by gradual deterioration of organs and cells along with loss of function
Extraction / Cytosolic catabodies /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.
Catabodies / 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.
Stem Cells and Suicide genes, senolytics, immune stimulation / 6-thiodG 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 (including adipose fat aging) to senescent cells diminishes, resulting in an imbalance that constitutes a major origin of aging (becoming decrepit / degenerative). Cancer could now be destroyed with fluorodeoxyuridine, a nucleotide analogue, being used in a clinical trial in Australia by Maia Biotechnology. Fluorodeoxyuridine turns telomeros into a sucide gene.
IF1 inhibition / Gene drive / 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.
Age breaking molecules/enzymes/ stimulation of resynthesis 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.
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.
Upper Video : relationship between Apoptosis (process of programmed cell death), Maintainance (Homeostasis) and good copies of the creator cells (Stem cells). Lipids under the skin serve as insulation, a protective barrier, and a source of energy. Major types include ceramides, fatty acids, and cholesterol in the skin's outermost layer. Lipid-containing adipose tissue is the primary source of adipose-derived stem cells (ASCs), also known as adipose-derived mesenchymal stem cells (AD-MSCs), which are multipotent cells with applications in regenerative medicine. The cells can differentiate into various mesodermal cell types, such as adipocytes (fat cells), osteoblasts (bone cells), and chondrocytes (cartilage cells). ASCs possess immunomodulatory properties, secrete factors that influence other cells and tissues, and are explored for treating inflammatory conditions and tissue damage. |
