Genetics and Life Extension: A Xanatos Research Focus
Who doesn't want to remain strong, healthy and vital well into their senior years? All of human history has told us that when we age, we become weaker, eventually succumbing to any of a stunning variety of the opportunistic diseases of aging, losing our freedom, strength and dignity in the process. This is a universal tragedy - we know of very few other forms of life that have an experience any different from this.
Something New Under the Sun
Something came onto the radar of Xanatos Research back in 1996 that had direct, and stunning, implications for Lifespan and Healthspan Extension possibilities. Sections of DNA that were previously thought to be an accumulation of "junk DNA" were instead discovered to be protective and regulatory structures of great importance. These DNA sections were subsequently called "Telomeres". Shorter in elderly populations and people with rapid aging diseases like Progeria, Telomeres were discovered to be the cellular aging clocks of the body. One of the primary mechanisms of cellular aging had been discovered. This was an incredibly significant breakthrough. Concurrent with this discovery was the discovery of an enzyme that, in certain cell cultures, restored lost Telomeres during cell replication. This enzyme was termed "Telomerase". And thus began an unprescedented period of fruitful research into both the age-reversing effects of extending Telomeres, and the methods to do so. This research extended to not only to the reversal of the aging process, but also to potentially stopping cancers in their tracks. Something incredible had been uncovered.
First the Lock, Now for the Keys: Small-Molecule Activators, CRISPR-Cas9 and Gene Therapies Offer Answers
After several years of research, and seeing the effects of activating Telomerase in cell cultures in the body (see studies such as this, on mice - or see image on right), it became obvious that an efficient and safe methodology of activating Telomerase in cell cultures throughout the body was necessary. Initially, the focus was on small-molecule activators, such as cycloastraganol, but they only activated approximately 20% of the Telomerase in cell cultures body-wide. But in 1987, Osaka University researchers Yoshizumi Ishino and his colleagues accidentally discovered what has become known as the CRISPR-Cas9 DNA Editing System (to learn more about CRISPR, view the link at https://en.wikipedia.org/wiki/CRISPR for a good introduction.) In short, the CRISPR-Cas9 system allows us to literally cut and paste DNA sequences using whatever template we generate. It allows us to precisely snip out genes that are less-than-optimal for certain tasks, and substitute gene sequences that perform functions we wish to activate, such as turning on the Telomerase enzyme in cell cultures. And fortunately, it turns out that using CRISPR-Cas9 is very easy, although it is not without its quirks... among which is that while the templating action of the system is very robust, DNA sequences often have VERY similar sequences which are NOT what we want to edit, so research is underway to create systems with double or triple redundancy to ensure that the section edited is exactly what we want to edit. Ultimately, rather than biochemical Telomerase activators, it is likely that an augmented CRISPR-Cas9 system will be the preferred method for full system-wide telomerase activation, perhaps, even into the germline cells themselves.
While CRISPR-Cas9 looks like a very robust candidate for Telomerase activation, and with a variety of protocols for transferring the edited genetic sequences to the host (Nucleofection, Electroporation, Lipofection, etc.), Genetic Therapies have also been put forward as methodologies to make Telomerase Activation available as a clinical therapeutic technique. One extreme, and it should be duly noted, controversial, example, is BioViva Science's founder Liz Parrish. In September, 2015, Liz flew to Colombia to receive a series of injections of her companies Telomerase Activator and another anti-aging solution designed to combat age-related deterioration of muscle mass. She had to do this in Colombia because regulations in the US prevented her from using her own developed compounds on herself - she could have literally not only lost her professional credentials, but also faced significant punitive legal actions, including jail time. Her subsequent testing - again, not without controversy - seems to have indicated a statistically significant increase in telomere length in the tested cell cultures. While her science seems worthy of consideration, only time will tell if her methods have, in fact, proven out. (Reference articles here, here, and here.)
A Deeper Dive
What are Telomeres?
The work of Geron Corp., and others, including the Whitehead Institute in Boston, MA., had been to discover methods by which the enzyme Telomerase, which is an enzyme that is able to be produced by human cells, but is not normally, may be "switched on", to allow healthy cells to continue to reproduce indefinitely. This research has been successful in-vitro on samples from a number of human tissues. Cells which have a normal replicative lifespan of 50 to 100 generations are still humming along at more that double or triple their natural lifespan, with no sign of mutation or cancerous deviations. The process is not as hard as one might imagine, and once regulatory approval can overcome the climate of uncertainty, clinical applications should begin to enter the marketplace. Major pharmaceutical corporations such as Upjohn and Pharmacia have poured large sums of money into developing this and its sister research, turning OFF telomerase stop cancer in its tracks, in an effort to bring the fruits of this labor into our lives.
While there is no way of knowing exactly how long this breakthrough will extend our lives, if we have discovered this much now, the extra time it buys us may allow us to live with excellent health many, many decades beyond what we would have lived without it, and perhaps past the point of the next significant breakthrough in extending the human lifespan. Perhaps, some of us reading this now may still be alive a hundred years hence.
TELOMERES in human beings are a repeating sequence of three of these
nucleotide units: Thymine (T), Adenine (A), and Guanine (G), in the sequence:
Each base unit is connected to a sugar via a beta glycosyl linkage. Both ends of the strands contain telomeres, and both the 3' and 5' strand contain these end sequences. The normal bonding pairs Adenine with Thymine, and Guanine with Cytosine, in a relationship known as complementarity.
Now, you might be asking "What can I do in the meantime to keep my body healthy while I wait to have my telomeres extended?". Well, eat healthfully (eliminate sugar, and sugar substitute; excessive carbs and simple starches as they convert to sugar in the body), get good exercise, have a good outlook on life, and take lots of GOOD vitamins (and load up on Omega Three Fatty Acids) to slow existing damage due to free radicals, homocysteine, etc. Reduce your inflammation load (have your doctor check your C-Reactive Protein levels) and take anti-inflammatory supplements such as Zyflammend (avoid other NSAIDS if possible.) Check out The Life Extension Foundation, (http://www.lef.org) where you can read about the latest life extension vitamins and drugs, as well as research on telomeres and other life-extending therapies.
You may also visit Geron Corporation, (http://www.geron.com), the original researchers that spearheaded this breakthrough. There you will find their current focus of resaerch (currently turning Telomerase OFF in cancer cells and forcing them to literally burn themselves out of existence.)
If you are familiar with searching the Human Genome Databases, try NCBI (http://www.ncbi.nlm.nih.gov), and see if you can discover the next breakthrough in life extension and novel genetic therapeutics...
Resources (to be organized)
Human TR (451 nt)
University of Utah Codon Decoder Chart