Wednesday, 1 July 2015


Lifespan Extension

If we look at aging as a genetic disease - by curing it we may be able to prevent most of the non-infectious diseases including cancer, cardiovascular and diabetes. However exciting may be this prospect for all our intelligence we have made very little progress in finding a cure. Shall we in the future be able to find the cure? - absolutely yes. Pioneering scientists have been able to identify 2-3 pieces of this jigsaw puzzle in recent times. We don't know that is 3 out of 30 total pieces or 3 out of 100 or 3 out 1,000. We may stumble upon the cure in 2 years or we may take 200 years we can't say. 
With the incredible gift of intelligence it is a shame that after gathering knowledge it all rots into dust. An intelligent species deserves to also be gifted with extended life spans to make best use of that knowledge and continue to evolve it rather than in jerks and bounds - constantly interrupted by deaths of brilliant minds just revving up. In our Universe everything that we have observed so far tells us that death is certain for all celestial objects - Mayflies with only 24 hours to a Sun which is 9.5 billion years. If something else in this Universe can have a longer lifespan than so can we.
Aging could be coded in our DNA 
Precision Nutrition has a very good write up about how we die:
Fascinating fact: The molecular clock in our germline cells — those from which our offspring are made when egg and sperm combine — is kept at zero. If it weren’t, babies would actually be born at Mom or Dad’s age!
If ageless cells already exist, this means we could be immortal one day. It’s possible at least in theory.
Why, then, do we age?
We don’t completely know for sure.
What we do know is that it takes a lot of energy to maintain cells and repair the damage that occurs throughout a lifetime. Wear and tear takes a toll. Cells break down, much like cars.
DNA damage in our cells’ nuclei and mitochondria start to accumulate. Meanwhile, the older we get, the harder it is to repair things. At a certain point, the damage is bad enough, and widespread enough, that our cells can’t fix it.
This means our cells (and our tissues) oxidize, become inflamed, and/or fill up with waste. Which leads to chronic diseases like cancer, metabolic disruptions, and/or neurodegenerative disease.
And — in case you haven’t noticed — this functional decline ends in death. This is one of the most popular theories about cause of aging and death.

Please find below information on some of the light that has been shone on the dark mystery of aging:
Of all the various approaches there are only two so far which seem to show significant potential in reversing and repairing the damage of aging. That does not mean we have proof that they will extend our life span as that would take very long to be found out but repairing some of the major damages of aging may provide a life without non-infectious diseases and youthful vigor which in itself is a major breakthrough. These two incredible findings are described below along with another major discovery from a Harvard Medical School Lab and some very early stage but promising research in telomeres and cell senescence:

Parabiosis is surgically joining the blood circulation of two living organisms. Bert was awarded the Experimental Physiology Prize by the French Academy of Science in 1866 for his pioneering experiments in parabiosis. In the experiments blood from a young mouse is circulated in an old mouse. The young blood transforms many of the key organs and systems of the old mouse back to its younger state. In recent experiments scientists like Wyss-Coray of Stanford, Amy Wagers of Harvard, Villeda of UCSF have discovered miraculous rejuvenation of brain, heart, liver and skeletal muscle - reversing brain and heart disease and making them function like a young mouse. It developed new blood vessels in the brain of old mice, induced muscle healing, stimulated regeneration of heart and liver reversing the damage caused by aging!
Dr. Harold Katcher does not subscribe to the popular wear and tear theory of aging. He believes aging and death is programmed in us by Nature. That is why attempts to cure symptoms of aging has not led to any major breakthrough so far. He believes that when young blood plasma circulates in older bodies it will uncode programming that will take back the body to its younger state. As long as this is done regularly the older human can revert back to their youthful state and remain there. Dr. Harold Katcher believes that Heterochronic Plasma Exchange extracted from a young human and injected into an old human should reverse many age factors. Apparently this is safely administered from many years for some diseases (not young for old). So safety is not a concern. There is equipment to do plasmaspheresis. A young donor can provide plasma twice a week. This is not an idea that may become a cure in the future but something that can be administered safely today by any physician. It should lead to old humans getting new hair, younger skin, improved memory, youthfully robust heart, muscles and liver, etc. Will this actually prolong life indefinitely or only improve old age we will find out as human experiments and trials are adminsitered by the pioneers.
Anti-Aging Brain Health
It has been proven in multiple experiments that by consuming 30-40% less calories CR has prolonged life in dogs, rodents, worms, flies, yeast, different kinds of bugs, and (arguably) non-human primates by 30 to 50 percent. That would translate to living till 120-150 years in humans. But CR is difficult to follow for life time and can cause some undesirable side effects related to deficiencies.
Nature has inserted in many species a silent, hidden, secret weapon that stays dormant all your life and is activated only under certain level of biological stress like a famine, or prolonged fast or severe calorie restriction in us and like boiling or cooking in plants. When a certain threshold is crossed of the biological stress, in prolonged fasting it means atleast 7 days, the body flips a regenerative switch to help us survive the stressful event. In this regenerative mode old dying or damaged cells due to wear and tear which stop dividing and clog up tissues and organs are cleared out and new pluripotent stem cells circulate through out the body repairing and rejuvenating us. This has been proven to enhance immune system and would also prevent age related diseases. It reduces an enzyme called PKA which has been reported to result in extended lifespan in organisms. Many of these exciting results have been obtained by Valter Longo, Edna M. Jones Professor of Gerontology and the Biological Sciences at the USC Davis School of Gerontology and director of the USC Longevity Institute. Longo has a joint appointment at the USC Dornsife College of Letters, Arts and Sciences. He said, "We could not predict that prolonged fasting would have such a remarkable effect in promoting stem cell-based regeneration of the hematopoietic system." He observed that, "PKA is the key gene that needs to shut down in order for these stem cells to switch into regenerative mode. It gives the OK for stem cells to go ahead and begin proliferating and rebuild the entire system. And the good news is that the body got rid of the parts of the system that might be damaged or old, the inefficient parts, during the fasting."
For the first time in recorded human history in an experiment on mice two year old was reversed to that of a 6 month old mice - in human equivalent a 60 year old reversing to a 20 year old! This landmark experiment was conducted in the labs of David Sinclair an expert in genetics at Harvard Medical School and reported in December 2013. Fortunately this has come from highly qualified researchers of an institution of the highest reputation but unfortunately David Sinclair has also caused a major fiasco before with no less than Glaxo writing off US$ 720 million that it invested to buy Sinclair's start up Sirtris Pharma which offered promising results in lab animals of their resveratrol Sirtuin1 activators which promised to have anti-aging properties. Not all experiments that succeed in lab animals translate into similar success in humans. This was a very expensinve lesson learnt by GSK which shuttered Sirtris after not finding any significant results in clinical trials on humans.
Despite this baggage the logic behind the new research finding of David Sinclair Lab does make one hope that this time the results do translate to humans as well.
His lab's researchers discovered that the nuclear DNA — found in the nucleus of a cell — and the Mitochondrial DNA — found in other parts of the cell — stop communicating as we age. Over time this loss of communication reduces the cell's ability to make energy, and signs of aging and disease become apparent. His team found the communication problems were down to a depletion in a protein called NAD+. When they upped the levels of NAD+ - Nicotinamide Adenine Dinucleotide - in the cells of mice, the ageing process reversed. The compound nicotinamide mononucleotide NMN used by Sinclair's lab to up the levels of NAD+ is naturally occurring in us and therefore safe so why isn't everyone taking it to reverse their aging to youth? Apparently it is extremely expensive - injections that would need to be taken daily may cost up to US$ 50,000 a day. Instead companies have discovered other precursors of NAD+ which are not so difficult to manufacture as daily pills. The issue is there are no clinical trials to prove that they work in humans and also what would be the dose at which they work. In the absence of this sceptics of David Sinclair claim this is one more of his utopian research with no practical use in humans. The two companies that are manufacturing the precursors one of which is co-founded by Sinclair may conduct reliable human clinical trials and our planets aging population has to await those results with bated breath.
Rejuvenating Mitochondria
Lifextension Inc.

Teleomeres are like time keepers and come with finite length like shoe lace caps at the end of cells. They continue to shorten as the cell divides. Once they run out, the cell would stop dividing and die causing aging related problems eventually leading to death. Many successful experiments in lab animals has shown increase in lifespan ranging from 13% to 40% by various approaches including:
a) Stanford scientists have found a way to lengthen the telomeres by a 1,000 nucleotides against typical 8,000 to 10,000 nucleotides. Thereby increasing cell life marginally. 
b) Salk Institute scientists have discovered that keeping DNA more stably packed in our cells it may be possible to slow or reverse aging,
c) Another group of Salk Institute scientists discovered that there is a cellular toggle switch which turns telomerase on and off. Telomerase enzyme can replenish shortened telomeres to allow cells to continue dividing and not dying. 
d) In a very interesting and novel approach Spanish National Cancer Research Centre scientists have used gene therapy for successfully lengthening lifespan in mamals safely with only a one time therapy! They have used a modified virus to deliver telomerase into cells thereby replenishing telomeres. They lengthened the lives of rats by 24% (one year old) and 13% (two year old). Their treatment did not cause cancers.

All the above telomere and telomerase research is at a very early stage and far from human clinical trials.

Telomerase elongates telomere