Grim Age and a fundamental contradiction

 

2019 is also important for the experiments by Horovith that showed an AI computable statistic that connect methylation concentrations of cytosine in Cp blocks of the DNA, habit indices of things like smoking and predict the remaining life in years to 98% accuracy. This is called the Grim Age counting the years remaining to natural death. To the surprise of Horovith team, the damage from Smoking errored on add when the damage was already reflected in methylation alone IE habit percentages of many damage elements like drinking were already reflected in methylation levels! The number remaining in natural life were called the Grim age. Unmodified Grim age was a better number than human memory of degree of smoking!

As this reference shows, There are many question in your mind about the establishment of Grim age in DNA m Age. While the entire blog is very readable, I do believe the author believes in some programmed theory of Aging and considers the modifications from habits a perturbation in predicted age, I still cling to the minority view that aging is damage accumulation and smoking and other lifestyle habits increase damage but still reflect the summary of damage accumulation. Damages can be external and unavoidable as a consequence of passage of time. But this means that the essential amelioration theory is neither prevention (gerontology) nor dealing with consequence (geriatrics) but deal with fixing the damage however caused (SENS and Dr. Audrey de Grey). Wounds happen in a war, prevention is like bullet-proof vests help, Complex consequences will require complex studies, that is what medicine is all about, better is to save the wounded and stabilize the wounded to be processed properly. Aging is like that. Let us fix the person ready to die. In fact in a war, Enemy will likely change the bullets once the vests become common, viral enemies will evolve to those that will defeat the aging fixes and the war will continue!

The best part of a blog is to read good comments and responses.

Some anti-aging candidates seem to have no effect on methylation status-like rapamycin for example.

In addition to DNA methylation covering various stretches of DNA we also have lamin A protein (which are defective in progeria), chromatin proteins, DNA helicase subunits that attach to and differentiate stem cell DNA (defective in Werner’s Syndrome) telomeric DNA which folds over on coding DNA So I would bet we need a lot more than a DNA methylation clock to get a more accurate predictor of lifespan.

One approach is very controversial and is outside my thinking. The DNA end are called telomere and become smaller in both the daughter cells on division. Around 50-60 divisions later, the telomere reach the limiting amount and cells die thereafter. The division limit is called Hayflick limit. The enzyme telomerase fixes the shortening telomeres by extending them.

The problem is that the cells that do not obey the limit and are infinite lived are cancer cells! Telomerase might induce cancers. Some claim not. There started a trial in Columbia where the clinical trial selects had to pay million dollars first! Like all free press people, I said the trial was a sham done in Columbia to dodge USA laws. I insist the direction is fraught with dangers, but the blogger above seems to have a reference here. I will not go there, but I have no hard reason to prevent you.

 Nevertheless, the Blasco lab was able to show that the shortest telomeres in the mice were elongated, and that markers of health including insulin sensitivity were improved by short-term treatment with TA-65, designed to increase telomerase.

Blasco’s lab then worked with a more potent (though more dangerous) method of telomerase induction: infection with a retrovirus engineered to introduce telomerase into the nuclear DNA of the infected cell.  “Treatment of 1- and 2-year-old mice with an adeno associated virus (AAV) of wide tropism expressing mouse TERT had remarkable beneficial effects on health and fitness, including insulin sensitivity, osteoporosis, neuromuscular coordination and several molecular biomarkers of aging.” (Bernardes  de Jesus, Vera et al. 2012)  The mice lived 13% longer when AAV treatment began at age 2 years, and 24% longer when treatment began at 1 year.  There was no increase in cancer incidence.

Telomerase can be induced by Cycloastragenol, suspected of being the main compound in TA-65. If you get cancer, I warned you.

 

Fundamental contradiction

 Cells become senescent at some point because of errors in duplication, hitting the Hayflick limit or environmental poisoning. Another reason is ignoring apoptosis. Such cells express SASP afterwards and just stay on.  One consequence is that NAD+ causes inflammation of neighbor cells, just evolutionary multi role of this vital chemical. This is suppressed by CD38, an essential chemical but that also has a role in death of neighbors. Thus, more cells become senescent! So my initial idea of reusing own plasma in TPE after CD38 the villain is extracted won't work as it is another cancer otherwise. NAD+ goes bad in this rare case. So we have a fundamental contradiction as CD38 is both a hero(too many benefits) and villain (fixer causes aging)! Just increasing NAD+ or removing CD38 is not going to work. The only way around seems to be making cancers in most cases a gentler disease.

Cancer Response to Therapy-Induced Senescence: A Matter of Dose and Timing 

 Cancer is a consequence of many naive fixes. Another example above was adding telomerase to bypass Hayflick limit, one has possible cancer problems. Even using existing cancer victims fails as even if their cancer is subsequently fixed, who knows how many new cancers were created for whenever. It might even be caused by senolytics.

At the same time, know that cancers are thought of as terrible diseases because they are tied to devastating chemo therapy etc and not mildly painful diseases that they are and ultra modern treatment is My own sister has been afflicted twice in Boston and things were not so bad in the USA! Of course, one might just think so, psychological terror same, and the relative toleration be from early diagnosis both time. The worst thing a patient can do is avoid or delay seeking a diagnosis.

An important sidebar

 Given the state of oxygen supply, I strongly support the use of proning by doctors to know and advise their non-ventilator patients and general knowledge of you as patient yourself and helper to a sufferer. Proning is laying the patient chest down and fast large gulps of air at speed as if panting. This method is advocated by Dr. Guleria, director of AIIMS, Delhi, applied to a big-shot in government who lost his oxygen and was forced into proning. This trick was invented by US residents, interning in the USA, one year back.