Benefits of Telomeres in Reversing Age & Gene Therapy

Telomeres are essentially the “butts” of single cell chromosomes. They are the tail end of a repetitive DNA structure that is highly related to your typical sequence of DNA that has undergone replication over and over again in a very distinct manner. A telomere will first neutralize a chromosomes’ predisposition/pre-programmed instructions to shorten with copy it makes. In other words, Telomeres are what helps to protect the very instructions of life from rapid deterioration that we call aging.[1] This has let to a tremendous amount of interest in trying to manipulate the gene into change the very coding in our chromosomes to further delay or possible even reverse the process of senescence.

What Are Telomeres? (VIDEO)

The first known account of the amazing natural phenomenon was reported by Russian scientist Alexei Olovnikov back in March of 1971. Dr Olovnikov later won a Nobel Prize for his findings. Doctor Olovnikov was the first to suggest that a tiny fraction of DNA sequencing is lost in every “copy” and replicative stage until the point when it reaches a critical level. After this level/age cell division would just stop. This stage is known as apoptosis. In cell division and cell differentiation, specific enzymes help copy our chromosome so DNA does not duplicate to the exact end part of a chromosome and can reach a total length of nearly 15,000 base pairs.

Today, we generally believe that the immortal DNA strands somehow avoid Telomere loss. Most scientists around the world believe that healthy Telomere play a critical role in the stability of our chromosomes. Most scientists also believe that the very act of growing old/aging hinges directly on the act of replicative senescence. [2]

End replication problem is a term to describe when cells divide without telomeres. Telomeres’ basically act like little disposable buffers at the end point of chromosomes. [3] These end points are totally consumed during cell division and thereby help to naturally replenish through this enzyme.

Telomerase are also being tested in gene therapies for treating cancers. Cancer cells divide at nearly 15-20 times the rate of normal cells. It is believed that if telomerase activity could be turned off with gene splicing then telomeres in the cancer cells would basically not divide as fast just like help to do in regulating normal body cells. By controlling how fast the cancer cells divide, we would be able to prevent the rapid spread of cancer cells in the early stages of uncontrollable replication.

Telomere have been known to help Reverse transcriptase “RT” and are also used in theraputic cloning. The benefits of the use of telomere in regenerative medicine especially for anti-aging treatments rest on the fact that the entire life activity of telomeres is essentially controlled by only 2 mechanisms: erosion & addition. If we can slow the erosion process we may be able to manage our aging more aggressively than mother nature can.

Can we tap the “Fountain of Youth,” simply with a shot of telomerase?

No. Currently there has not been enough research,clinical tests or practical applications in this area of microbiology. Any company,product or service claiming otherwise is false. Be cautious of any pills, peptides, injections, serums or creams claiming the active involvement of Telomeres. Taking such products is likely dangerous and will lead to more harm than good.

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Published Clinical Citations

  • [1] ^ Lurdes Planas, Elena Garcia Arias-salgado, Ana Montes Worboys, Pilar Rivera Ortega, Vanesa Vicens-Zygmunt, Roger Llatjos Sanuy, Patricio Luburich Hernaiz, Ignacio Escobar Campuzano, Elisabeth Arellano, Eva Balcells, Julio Cortijo, Ernest Sala, Jordi Dorca, Rosario Perona, Maria Molina-Molina, Biological age instead of chronologic age as prognostic factor in IPF: clinical implications of telomere shortening, QJM: An International Journal of Medicine, Volume 109, Issue suppl_1, September 2016, Page S10, https://doi.org/10.1093/qjmed/hcw124.004

  • [2] ^ K. Al-Issa, L.B. Tolle, A.S. Purysko, I.A. Hanouneh, Short telomere syndrome and fibrosis, QJM: An International Journal of Medicine, Volume 109, Issue 2, February 2016, Pages 125–126, https://doi.org/10.1093/qjmed/hcv115

  • [3] ^Ram Naikawadi, Supparerk Disayabutr, Benat Mallavia, Matthew Donne, Gary Green, Jason Rock, Mark Looney, Paul Wolters,Telomere Dysfunction in Alveolar Epithelial Cells Causes Pulmonary Fibrosis: Role for TRF1 , QJM: An International Journal of Medicine, Volume 109, Issue suppl_1, September 2016, Page S67, https://doi.org/10.1093/qjmed/hcw120.032

Obligatory Asymmetric Replication Asymmetric Cell Division

Obligatory asymmetric replication is also known as asymmetric cell division is the process by which a stem cell undergoes differentiation or division.  The final result of which are two daughter cells. [1]

One cell is identical to the mother cell and the other a totally differentiated one. This is one of the processes in regenerative medicine that allows stem cells to undergo to maintain their number and form a “stem cell reserve.” The other process is known as stochastic differentiation.

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Published Clinical Citation

  • [1] ^Ralph A. Neumüller,Juergen A. Knoblich Dividing cellular asymmetry: asymmetric cell division and its implications for stem cells and cancer Genes Dev. 2009 Dec 1; 23(23): 2675–2699.
    doi: 10.1101/gad.1850809

IVF In Vitro Fertilization Artificial Insemination

The word “In vitro” Latin translation, is simply “in glass.” In modern times this means an in-vitro environment is simply in a test tube or laboratory dish that holds the cell culture medium or substance necessary to perform a culture test or fertilization.[1]

How IVF Works

In vitro fertilization or IVF pertains to the artificial method of uniting the sperm with the egg. [2] In-Vitro or IVF treatments are usually performed in closed system laboratory environment by Stochastic Differentiation and directed self differentiation instead of the “traditional” and natural process that occurs in a human female body.

IVF treatments are typically used by families who are having difficulties conceiving. IVF is also a way to clone embryonic stem cells and in genetic Pre-Implementation Diagnosis testing or PGD testing for short. PGD when combined with IVF genetic screening can allow us to screen over 130 know genetic deficiencies and diseases as early as 8 days after artificial conceptions.[3]

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Published Clinical Citations

  • [1] ^ Fauser, Bart C J M, and Gamal I Serour. 2013. Introduction: optimal in vitro fertilization in 2020: the global perspective. Fertility and sterility, no. 2. doi:10.1016/j.fertnstert.2013.06.029. https://www.ncbi.nlm.nih.gov/pubmed/23905706

  • [2] ^ Iyoke, C A, G O Ugwu, F O Ezugwu, L O Ajah, and S G Mba. The role of ultrasonography in in-vitro fertilization and embryo transfer (IVF-ET). Nigerian journal of medicine : journal of the National Association of Resident Doctors of Nigeria, no. 3. https://www.ncbi.nlm.nih.gov/pubmed/24180141

  • [3] ^ Jin, Hai-Xia, Zhi-Min Xin, Wen-Yan Song, Shan-Jun Dai, and Ying-Pu Sun. Effects of human cumulus cells on in vitro fertilization outcomes and its significance in short-term insemination. The Journal of reproductive medicine, no. 1-2. https://www.ncbi.nlm.nih.gov/pubmed/23447919

Macrophage Markers Function and Activation

Macrophage are specific type of WBC or white blood cells, which are known to have a versatile functionality inside and for the immune system.

Dendritic Cells and Macrophages (VIDEO)

Macrophages are known as the body’s first line of defense against invasion from viruses and bacteria, Macrophages are generally responsible for safeguarding our inter-cellular environment by killing several types of bacterias.

During the time of infection or tissue damage,monocyte cells leave the bloodstream and rush to the affected organs such as liver and kidney or other tissues to differentiate into becoming become macrophages. These macrophage cells can modify themselves into forming different types of cell structures to fight different microbes and viruses.[1]

Humans macrophages are only about 22 micrometres in diameter.[2] They can survive for several. Macrophage cells are also involved in the development of innate immunities. Different macrophages have different protein markers on their exterior surfaces.

Examples of known macrophage markers include:

  • EMR1
  • MAC-1
  • MAC-3
  • CD11b
  • CD14
  • CD68
  • Lysozyme

Cellular Immunotherapy

Our stem cell doctors are able to identify such specific markers using a device known as a flow-cytometer.[3]

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Published Clinical Citations

  • [1] ^ Chatterjee, Priyajit, Soma Seal, Sandip Mukherjee, Rakesh Kundu, Sutapa Mukherjee, Sukanta Ray, Satinath Mukhopadhyay, Subeer S Majumdar, and Samir Bhattacharya. 2013. Adipocyte fetuin-A contributes to macrophage migration into adipose tissue and polarization of macrophages. The Journal of biological chemistry, no. 39 (August 13). doi:10.1074/jbc.C113.495473. https://www.ncbi.nlm.nih.gov/pubmed/23943623.

  • [2] ^ Roger, Thierry, Julie Delaloye, Anne-Laure Chanson, Marlyse Giddey, Didier Le Roy, and Thierry Calandra. 2012. Macrophage migration inhibitory factor deficiency is associated with impaired killing of gram-negative bacteria by macrophages and increased susceptibility to Klebsiella pneumoniae sepsis. The Journal of infectious diseases, no. 2 (November 2). doi:10.1093/infdis/jis673. https://www.ncbi.nlm.nih.gov/pubmed/23125447.

  • [3] ^ Sun, Yu, Yu Wang, Jia-Hui Li, Shi-Hui Zhu, Hong-Tai Tang, and Zhao-Fan Xia. 2013. Macrophage migration inhibitory factor counter-regulates dexamethasone-induced annexin 1 expression and influences the release of eicosanoids in murine macrophages. Immunology, no. 2. doi:10.1111/imm.12135. https://www.ncbi.nlm.nih.gov/pubmed/23777345.

Human Embryonic Stem Cells hESC Therapy

Human embryonic stem cell line or hESC are also referred to as simply Embryonic stem cells. ES cells pertains to a pluripotent lineage of cells that are typically derived from a human embryo (after zygote) at its earliest stage.

 Embyronic Stem Cell Biology

Embryonic cells of the morular are totipotent. ES cells are considered very powerful in regenerative medicine since they can undergo cell division even without differentiation, which could go for extended periods,[3] and eventually develop into the cells composing the three germ layers.

There are 3 types of pluripotent cells that occur:

    • Embryonic Stem (ES) Cells. ES Cells can be isolated in the lab from the ICM or inner cell mass of a blastocyst.Embryos for ES cell treatments are usually produced naturally during IVF therapy. In most countries around the world including Thailand, harvesting ES cell lines from human donated blastocysts forbidden because the belief that it destroys a human embryo
    • Embryonic Carcinoma (EC) Cells are is the 3rd type of pluripotent cell that can be isolated from teratocarcinomas (occasional tumors in the gonads of a fetus)
    • Embryonic Germ (EG) Stemcells can isolated from the precursor to human gonads but requires aborted fetuses.

[1]

All 3 of the previous ES cells typically require isolation from fetal or embryonic tissue. Some ES lines such as induced pluripotent cells however can now be can be cultured in our labs using special growth medium but are still very difficult to control during mesoderm production and the differentiation process.[2]

The Regeneration center of Thailand does not use Embryonic stemcell lines in any of its treatments. Our cell therapies use allogeneic or autologous Adult stem cells only.

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Published Clinical Citations

  • [1] ^ Yang, Heung-Mo, Sung-Hwan Moon, Young-Sil Choi, Soon-Jung Park, Yong-Soo Lee, Hyun-Joo Lee, Sung-Joo Kim, and Hyung-Min Chung. 2013. Therapeutic efficacy of human embryonic stem cell-derived endothelial cells in humanized mouse models harboring a human immune system. Arteriosclerosis, thrombosis, and vascular biology, no. 12 (October 3). doi:10.1161/ATVBAHA.113.302462. https://www.ncbi.nlm.nih.gov/pubmed/24092748

  • [2] ^ Soteriou, Despina, Banu Iskender, Adam Byron, Jonathan D Humphries, Simon Borg-Bartolo, Marie-Claire Haddock, Melissa A Baxter, David Knight, Martin J Humphries, and Susan J Kimber. 2013. Comparative proteomic analysis of supportive and unsupportive extracellular matrix substrates for human embryonic stem cell maintenance. The Journal of biological chemistry, no. 26 (May 8). doi:10.1074/jbc.M113.463372. https://www.ncbi.nlm.nih.gov/pubmed/23658023

  • [3] ^ Hung, Sandy S C, Raymond C B Wong, Alexei A Sharov, Yuhki Nakatake, Hong Yu, and Minoru S H Ko. 2013. Repression of global protein synthesis by Eif1a-like genes that are expressed specifically in the two-cell embryos and the transient Zscan4-positive state of embryonic stem cells. DNA research : an international journal for rapid publication of reports on genes and genomes, no. 4 (May 5). doi:10.1093/dnares/dst018. https://www.ncbi.nlm.nih.gov/pubmed/23649898

Gastrulation Germ Layer definition and formation in humans

The Germ layers consist of about three layers of cells:

  • Ectoderm – exterior germ layer
  • Mesoderm – middle germ layer
  • Endoderm – internal germ layer

These three distinct layers are formed after a blastocyst’s inner cell mass undergoes a process of specific organization called gastrulation,[1] which occurs after the blastocyst phase in embryonic development.

Organization or Gastrulation [2] involves many things including distinct differentiation patterns in human mesenchymal cell motility, cell shape, and cell adhesion.[3]

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Published Clinical Citations

  • [1] ^ Jiao, Fei, Juan Wang, Zhao-Lun Dong, Min-Juan Wu, Ting-Bao Zhao, Dan-Dan Li, and Xin Wang. 2012. Human mesenchymal stem cells derived from limb bud can differentiate into all three embryonic germ layers lineages. Cellular reprogramming, no. 4 (July 9). doi:10.1089/cell.2012.0004. https://www.ncbi.nlm.nih.gov/pubmed/22775353

  • [2] ^ Solnica-Krezel, Lila, and Diane S Sepich. 2012. Gastrulation: making and shaping germ layers. Annual review of cell and developmental biology (July 9). doi:10.1146/annurev-cellbio-092910-154043. https://www.ncbi.nlm.nih.gov/pubmed/22804578

  • [3] ^ Zoldan, Janet, Emmanouil D Karagiannis, Christopher Y Lee, Daniel G Anderson, Robert Langer, and Shulamit Levenberg. 2011. The influence of scaffold elasticity on germ layer specification of human embryonic stem cells. Biomaterials, no. 36 (October 1). doi:10.1016/j.biomaterials.2011.09.012. https://www.ncbi.nlm.nih.gov/pubmed/21963156

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