The Transition to a Longer Living Society Part 1

A 21st Century Theory of Aging

By George Tait Edwards MBE

1 Introduction

There is a new theory of aging that has been developed in recent years by Professor David Sinclair at the universities of MIT, Harvard and New South Wales. (See: https://www.youtube.com/watch?v=vCCdmGKtxPA) The theory he has developed is based upon the new concepts in epigenetics, on the idea that as people age, their genes are damaged by chemicals which open up the histones and cause part of the genes to express themselves when they should be silent.

2 Background

Human genetic material is composed of 46 genes in every human cell. The total length of the genetic material (if stretched out in the mind of man — it can never be unravelled in reality) would be about six feet long or about 1.8 metres. That length of genetic coding can only be contained in a tiny cell because it is wrapped in histones (which are a protective wrapping which silences gene expression) and the genetic spiral is further wrapped into a thicker spiral which in turn is wound up into the individual genes which fit together in the nucleus of each human cell. The loops of genetic material extruding from the cell nucleus should only be the expressed code sequences required to make and maintain the particular body part (e.g., the eye, the skin, the brain, the muscles, etc) to which the cell belongs. Unfortunately as people age, free radicals damage the histone wrapping and parts of the genetic material become inappropriately extruded and expressed rather than being wrapped and remaining silent.

3 The New Epigenetic Understanding

The genius of David Sinclair is that he and his associates have shown that many of the products which appear to extend human life and improve health are all acting through the same process. All of the many products — for example, resveratrol from the skin of red grapes, metformin diagnosed for Type II diabetics, NAD+ as a particularly active form of vitamin B3 and astragalus from Chinese medicine, and many others — as well as lifestyle changes such as dieting and exercise, all act by stimulating an improved activation of a substance called AMPK (the acronym for 5' Adenosine Monophosphate-activated Protein Kinase) which is the key repairer of the cellular genetic material. AMPK moves around within each cell snipping off the erroneously attached material and the histones re-wrap the genes which become correctly silent once more. Different activators might stimulate AMPK in particular kinds of cells.

4 Metformin’s Silencing Of Wrongly Expressed Gene Sequences

The expression of parts of genes which should be silent appears to be the major cause of a great deal of aging. Research has shown that people with type II diabetes who are taking metformin are about a third less likely to develop the three main diseases of aging — less likely to develop heart attacks, cancers and nervous system disabilities such as Parkinsons, Alzheimers or Motor Neuron disease. Furthermore, as Professor David Sinclair has pointed out, there are AMPK stimulants which are up to 500 times more effective than resveratrol and which may reduce the risks of these three main expressions of metabolic syndrome to very low, nearly nil, levels.

Metformin even in low doses appears to extend human lifespan by at least 10% while other AMPK activators may produce (if animal tests are any guide, and in this case they are) an increase in the lifespan of at least 20% and possibly up to 40%. Furthermore, the improvement in human health during the last four decades of their life is considerable — people become youthful, more healthy, and no longer need the drugs to deal with heart attacks, cancer, or CNS diseases. Because the drugs to treat these diseases are a major source of income to the pharmaceutical companies, the largest Pharma company in the world at first paid for much research criticising and denying Sinclair’s results. One of the largest Pharma companies in the world — GlaxoSmithKlein — in 2008 bought the company Sinclair co-founded, Sirtrus Pharmaceuticals, for $720m, see: https://en.wikipedia.org/wiki/David_Andrew_Sinclair

5 The Health Span Extension Is More Significant Than The Lifespan Increase

This extension of the healthspan much more significant than it seems at first glance. Recent advances in treating end-of-life diseases tend to prolong life in an unhealthy state. Some data suggests that about 40% of final years of men and about 42% of the terminal lifespan of women is spent poor health. (Sinclair makes much of this in the TedX youtube video from 6m 32s at https://www.youtube.com/watch?v=vCCdmGKtxPA ). Metformin and its AMPK-stimulating similars not only prolong life but also increase the health span so that life is lengthened in a healthy condition. That is a major effect and improves the quality of life in a way that treatments for cancer, strokes and senility do not.

6 The Future Major Causes of Death

If people don’t die from one of the three major medical causes of death — cancer, heart attacks, and CNS diseases (eg Parkinsons, Alzheimers, MS, and other such diseases) — then what, in future, are people likely to die from? The truth told in 1219 to Genghis Khan by the Chinese sage Changchun — that “Life can be extended, but death cannot be prevented” and hence everybody will die eventually of something, will remain forever valid.

It should be noted in passing that the insults offered to the usual functioning of the genes can be high enough so that these new pills would not prevent earlier death or disability. Sumo wrestlers, consuming 20,000 calories a day, are likely to continue living shortened diabetic lives, because while the AMPK activating pills can remove the daily damage done by normal food intakes, very high calories are likely to continue to produce heart attacks, cancers and CNS diseases. Absence of dieting and exercise reduces the healthspan. High levels of radiation may result in major cellular damage which these AMPK-stimulating pills cannot prevent.

There are a host of diseases to which this new epigenetic understanding offers no remedy. These are:

6.1 Externally Sourced Diseases

Epigenetic understanding now makes it clear that diseases have two major sources. The first of these — responsible for most (or over 75%) of the previous causes of death — are due to the mistaken expression of genes which should be silent. The new science of AMPK stimulation deals with many, perhaps all, of these. The second source of diseases are the externally sourced infections which have traditionally been responsible for many of the plagues and recent diseases of mankind — Aids, bubonic plague, malaria, yellow fever, etc. Externally sourced diseases are often able to be treated by antibiotics and viruses can sometimes be treated by injections (eg the cold and flu injections, Chicken Pox/Shingles injections, etc)

6.2 Genetically Pre-conditioned Diseases

Epigenetics does not offer any remedy to pre-existing genetic risks. Individuals with Progeria cannot be cured by a system which repairs damage to proper gene expression if the inherited genes are faulty. The same observation applies to all the actual or potential disabilities arising from defective inherited genes — for example Cystic fibrosis, Down syndrome, the BRCA1 and BRCA2 genes predisposing women to breast cancer, Duchenne muscular dystrophy, Haemophilia, and Sickle-cell disease, to name only a few (a more complete list is at https://en.wikipedia.org/wiki/List_of_genetic_disorders) are not likely to be improved by AMPK stimulation.

6.3 Viruses Eg Pneumonia

Viruses are not necessarily affected by AMPK stimulation except to the extent that stimulation improves immune responses. The effect of many mouth-entering viruses can be limited by small doses (eg 4gm) of Xylitol in a morning drink which acts as a false sugar and which kills viruses or diseases. Pneumonia may be completely prevented by a small daily dose of Xylitol, which seems to best attack hydrophilic viruses. BHT attacks the membrane of single-jacketed lipophilic viruses so it may be that both kinds of many viruses may be disabled by due doses in some circumstances.

6.4 Accidents From All Causes

Accidents and external events in the UK during 2011 accounted for about 17,500 deaths and such events will remain a major non-medical cause of death.

6.5 The Hayflick Limit

In 1961 Professor Leonard Hayflick demonstrated that human cells could only divide a certain number of times and then ceased to be able to divide and died. Cellular death appears to be related to the shortening of the telomeres which are at the sealant at the ends of the genes. It is known that telomerase lengthens telomeres, but because telomeres are longest in cancer cells that knowledge is often treated as ambiguous. Some substances, such as an extract of astragalus membranaceus, are alleged to extend the length of telomeres but the mode of this action appears unclear. And precisely why some humans have cells which divide 40 times while others have cells which divide 60 times seems unclear.

It seems that AMPK stimulation is a rectangularising technology, that is it may enable people to more often approach their maximum natural lifespan (of about 120 years at most) but the pills may not offer any escape from the Hayflick Limit although that Limit is now the subject of current and future research.

7 The Current Position

7.1 The FDA

The US Food and Drugs Administration (otherwise known as the FDA) have historically been difficult people to convince about anything. The FDA have recently agreed that Metformin should be studied as a life extension product for people. (See: http://www.prnewswire.com/news-releases/anti-aging-human-study-on-metformin-wins-fda-approval-300193724.html)There are two major reasons for that. First, animal studies have shown that Metformin extends the life of animals by between 20% and 40%. Second, some Type II diabetics, who previously had lives which are shorter than normal people by about 8–10 years (see length of life for diabetics) are now (on Metformin) living longer than non-diabetics by about 8 years due to the use of that prescription drug. AMPK activator, developed by the Life Extension Foundation (see: http://www.lifeextension.com/vitamins-supplements/item01907/ampk-activator) produces the same effects as (and possibly much greater lifespan results than) Metformin. See AMPK activator review and watch David Sinclair at: https://www.youtube.com/watch?v=vCCdmGKtxPA if you wish to understand how important this new development may be.

7.2 Is Further Research Really Necessary?

Existing research validates the beneficial effects of Metformin, and these positive effects are so great as to question why any further research is necessary. For example, the University of Cardiff conducted research lasting about six years to determine the most effective diabetes drug. That study covered 180,000 people of which 78,000 were treated with metformin. A control group of 90,000 non-diabetic individuals, matched for “age, gender, smoking habits and general health,” were also followed up, the study found out that the metformin-treated group lived longer and were significantly healthier than the non-diabetic group. See the 08 August 2014 Cardiff University news report about that exhaustive study:

http://www.cardiff.ac.uk/news/view/45575-can-people-with-type-2-diabetes-live-longer

It seems very likely that Metformin might increase the length of the healthy human lifespan by about 20% to 40%. That happens because Metformin stimulates AMPK production. The doses being given for Type II diabetes do not appear to be optimal for the greatest increase in the healthspan, but these smaller doses do obviously produce very significant results. It has sometimes been quoted that there are 7,500 peer-revised articles about metformin, and Google search lists 91,000 results to the enquiry “scholarly research articles” about metformin. It is a very well-researched drug.

Metformin is one of the safest drugs ever developed. It must be taken immediately before or with meals or it can produce diarrhoea. See the assessments at: https://en.wikipedia.org/wiki/Metformin.

7.3 There Are Many Other AMPK Activating Substances

Metformin, impressive although it is, is only one of a large number of AMPK-activating stimulants. The reported increase in lifespan of eight years for the metformin-taking group and the one-third reduction in metabolic diseases are only a starting position for the whole group of health-improving, lifespan-extending substances (few of which are drugs). As usual, the research has to be read in context. The Cardiff University Study average whole-group results of one-third reduction in metabolic syndrome diseases and the extra three years of life for the generally overweight, type II diabetes group are only an unintended side effect of metformin, which has been prescribed in low doses to treat metabolic syndrome. Adjusting for more normal weight the lifespan extension rises to eight years and the reduction of metabolic syndrome diseases appears to have a similar multiplier. If the required AMPK stimulating dosages were taken, perhaps 99% of such diseases may be averted. Metformin also often causes weight loss although the full effects may take up to three years. Taking metformin plus other AMPK activating stimulants reverses metabolic syndrome more quickly and lowers blood pressure and blood analysis fractions (eg chloresterol levels, HDL/LDL, etc) to more youthful levels, much to the surprise of doctors and some diabetic nurses.

8 Conclusion

The FDA tests are said to last for about 12 weeks. Some media are reporting that the results of the FDA tests might take 5 to 7 years to produce final recommendations. Given the existing evidence, that time scale seems more politically decided than scientifically required, because neither the US Government (nor any other government) have any policies designed to cope with an expansion in their population by perhaps 20% to 40% plus immigration during the next two to four decades.

But to ignore this new development is to condemn millions of people to unnecessary suffering and early death, both of which are now entirely preventable. Since, as the modern version of the Hippocratic Oath observes: ‘’I will prevent disease whenever I can, for prevention is preferable to cure’’ the prevention of heart attacks, cancers and CNS diseases is obviously better than the current partly disabling treatments, and holds out not only the hope but also the reality of a healthier longer life, cheaply achieved by the provision of a pill costing a few pennies a day.

Too see part 2 of this series of articles, see:

https://medium.com/@georgetaitedwards/some-economic-implications-of-the-longer-living-society-part-2-170dcccaf3b8#.7xy73t4fl

© George Tait Edwards 2016