Friday 25 September 2015

Pathways to longevity

Motto: Increased longevity without quality of life is and empty prize. (World Health Organisation - 1997)

Or as the immortal James Dean said: It is ideal to die young, but as late as possible. So tonight we will talk about pathways to longevity. What are they? Can we replicate them in order to work for us? The data is fascinating, but contradictory. It will be a long post, but i hope an interesting one, that will give you ideas about how to live long and healthier. Anyway here we can find some fun facts, like:

Hispanics less likely to live with disease. oldest-old age.
No education or black-white differences.
Former smokers more likely to live with disease compared to non-smokers.
Overweight/obese have greater disease burden throughout oldest-old age compared to normal weight at baseline.
No differences by region.
Older adults living in large metro areas at baseline more likely to escape disease.

Overall the life expectancy was 47.3 years in 1900, rises steadily to 68.2 years in 1950 and then slowly to 78.7 years in 2010. But what is interesting is happening after 2010, when an apparent tipping point is reached. At the present moment (September 2015), the life expectancy is increasing with 4 hours every week. 

Now we had some categories, one classification will see them as recoverers, delayers(long), delayers(short), survivors and escapers. Recoverers are the one that will have some illness, but will recover completely before reaching age of 100, Delayers will get sick after the age of 80 or 90, and will reach 100, but not completely healthy. Survivors will get unhealthy early, some starting from their 30-40, but still reach 100. Escapers are the ones that can reach 100 without any major health problems. Now, this is the segment on which we should focus our research and try to replicate. Sadly, only 19.5 of the centenaries are escapers. White, Black and Hispanic doesn't matter as percentage in being an escaper. Smokers and ones that never smoked are slightly more as percentage than former smokers, underweight, normal, overweight and obese got similar chances in reaching age of 100. 

Surprisingly, Terman 90 years ''life cycle study'' offered us some insights. And more than that, appears to be an array of benefits from religious and spiritual practices and experiences that benefit physical and mental health". ("Spirituality and the Aging Brain". Andrew B Newberg. Generations: Vol. 35. No. 2. Spring 2011. p.87,88). This is an important box to tick. Spirituality and life coaching is importat, more important than we think. In this age of technology, when we spend most of the time in front of our phones and tablets, of working overtime, this is some mind boggling truth. So i repeat, spirituality  need to have a very important place in our life. 

Second, fulfilling relationship and being a happy couple it is crucial in living a long healthy life. But how many of us dear to think at this. A long term relationship, no divorce, healthy sexual life, real emotional connection, financial independence, perfect mental health, all this up to 100 years or more. What are the odds? Very low, we would say. But is not true. We estimate that 75% of us will achieve this by the year 2100. 

Eating, this seems to be an important part in me majority of the cases, but is much harder to achieve today, even with all the organic, non GMO, healthy products available. Vegetarians have a small advantage versus the ones with a predominant meat eating diet, and we do not have enough data to differentiate in between vegans, vegetarians, pescetarians and all the slightly different versions of non red meat diet, but they do better than the average "fast food - fast cooking from prepacked" diet. Calorie restriction diet also had a result, but not as significant as we expected. 

Exercise is important, even as a voluntary act, or under the name of a very active career. But even here we experience variations, as seems to be more important to use multidisciplinary training like Parkour for example, for the unique health of the joints effect, gymnastics versus heavy weight training. Slow versus fast is not very different, even if yoga and Tai-chi fare better than gym, but a combination of both is working better. Running is good too, but in the end diversity seems to bring the most benefits, a mix of yoga, martial arts, athletics and swimming seems to be an example of  a good mix. Exercise extends average life span in rodents as well as humans, and it should be included in combination tests with other treatments, because exercise and medications can interact constructively or destructively.  Exercise signals the body for life extension with peroxide, which looks a lot like oxidative damage.  There is a stunningly counter-intuitive finding from recent years that anti-oxidants can interfere with the life extension benefits of exercise.

Science, we like to play with powers we do not understand completely, yet, but some results were achieved too. We have many disciplines related with this. Let's talk about each one using a short resume. 

Biochemical researches to make the youth pill is work in progress, and here we talk about substances like: 
a. CR mimetics / insulin  / IGF
(metformin, MCP - marine collagen peptides, dinitrophenol, resveratrol - extracted from red wine, pycnogenol - extracted from pine bark)
b. Anti-inflammatory - Anti-inflammation is once of the most promising avenues to life extension.
(aspirin, NDGA) - mixed results
c. Neuroprotection  
(ginkgo -  impressive life extension in rats, deprenyl - dopamine is a neurotransmitter that decreases with age.  Low dopamine levels in the brain are the proximate cause of Parkinson’s disease, and in this sense, we are all pre-Parkinson’s patients as we age.  Deprenyl is an MAO-B inhibitor, which means that, via indirect action, it inhibits the uptake and disposal of dopamine.  Deprenyl makes dopamine hang around longer.)
d. Mitochondria / ROS  
(SkQ, CoQ10 - Vladimir Skulachev has devoted the latter part of his career to a molecule of his own invention, which combines a chelated, positively charged ion at one end of a carbon chain with a CoQ10 molecule at the other.  The positive ion acts like a tugboat, pulling the molecule through the mitochondrial membrane into the mitochondrion itself, where the CoQ10 can do the most good.  Skulachev’s molecule, nicknamed SkQ, concentrates itself a million-fold inside the mitochondria, where it is needed most.  In experiments with life span and health span, the SkQ molecule (administered eye drops) has reversed cataracts and macular degeneration, and (administered orally) has has extended life span in mice.)
e. Anticancer
(green tea, melatonin)
f. TOR = Target of Rapamycin  
(rapamycin)
g. Increased autophagy  
(spermidine - autophagy is the name of the cell’s main clean-up process, eliminating accumulated wastes.  Spermidine promotes autophagy, and is found in many foods.  As an anti-aging agent, it has been championed by Frank Madeo of University of Graz. He reports dramatic life extension in worms and flies, and smaller life increases in life span for rodents.)
h. Miscellaneous or unknown mechanisms
(PBN, dinh lang, short peptides)

Telomeres - There are now many herbal extracts that are known to promote expression of telomerase, and (probably) work in vitro to increase telomere length.  Extracts of astragalus, milk thistle, horny goat weed, ashwagandha, turmeric root and fish oil have all shown promise in lab studies.  These substances are unlikely to extend life span in lab mice because, unlike humans, mice already express telomerase copiously through their lifetimes, and mouse telomeres are much longer than human telomeres.  But there are some rodents that don’t express telomerase, and they would make appropriate models for testing telomerase extenders alongside the above medications in life span studies.

This was the biochemical anti aging approach.

Many scientists have attempted to find the “Fountain of Youth.” Although many genetic and medical treatments have increased the average human life expectancy, these treatments have yet to increase lifespan over a hundred years.
However, this statement may no longer hold true in the future. In a recent issue of Nature Communications, Mitra Lavasani, et al. (2012) conducted an experiment involving fast-aging, genetically engineered mice. These mice have a usual lifespan of 21 days. A few days before the mice reached their predicted maximum life span, the injections were delivered at the Institute for Regenerative Medicine in Pittsburgh. The results were astounding. The elderly mice lived approximately 70 days – three times their normal lifespan. In human terms, that would be the equivalent of an 80-year-old living to be 200. Specifically, the investigators studied the effects of injecting muscle-derived stem/progenitor cells (MDSPCs) into a murine progeria model (fast-aging mice). Since age-related degenerative changes are universal in the musculoskeletal system, the impact on the musculoskeletal system by murine muscle-derived stem/progenitor cells (MDSPCs) became the primary focus of the experiments. MDSPCs are multipotent cells isolated from postnatal skeletal muscle. They have the capacity for long-term proliferation, are resistant to oxidative and inflammatory stress, show multilineage differentiation and self-renew, induce neovascularization, and stimulate regeneration of bone, skeletal, and cardiac muscles. These characteristics raise the possibility that the loss of MDSPCs or related perivascular progenitor cells could contribute to sarcopenia, osteoporosis and other age-associated degenerative diseases.

On Feb. 20, 2010, Gregory M. Fahy, PhD and Saul Kent interviewed Michael West, PhD, CEO of BioTime, Inc., about a new breakthrough published in the journal Regenerative Medicine. The paper reported the reversal of what Dr. West has called the “developmental aging” of adult human cells in the laboratory dish. Utilizing genes that grant our reproductive cells the potential for immortal growth, the researchers showed that it was possible to turn back the clock in human body cells, enabling the potential for young patient-specific cells of any kind for use in regenerative medicine. This research was funded in part by the Life Extension Foundation®. The name “regenerative medicine” came from Bill Haseltine, then of Human Genome Sciences, one of the early leaders in genomics and DNA technology. Back in the 1990, Bill learned that researchers in aging were making important progress on turning back the clock of aging in human cells through cloning, and then creating young cells that could potentially regenerate or repair all the tissues of the aged human body. And so, upon hearing of that realistic prospect, he christened the field “regenerative medicine” in the belief that it would one day become a major part of medical practice. So, based on its origins, I would define regenerative medicine as that collection of technologies that utilizes embryonic pluripotent stem cells and their derivatives to regenerate tissues in the body ravaged from disease, primarily degenerative disorders associated with aging.

Some researches focused on what we call the immortal cells. Early in the history of evolution, life existed as single cells, not unlike the protozoa swimming around in pond water today. These animals replicated by simply splitting into two new cells. They didn’t have to die and are therefore called “immortal.” In the following millennium, these immortal cells spun off specialized helper cells to help them compete in feeding and reproduction. These helper cells selflessly served the needs of the immortal cells and became what we call the “body” while the immortal cells became what we call the “germ line.” Since the immortal cells carried genetic information, they selected for the body to die after it served its purpose. Where are these immortal cells in you and me? In the adult human, they are the egg cells in a woman’s ovary, and the sperm-forming cells in the testicles of a man. When a sperm and egg unite, the resulting cells continue the germ line by forming a small cluster of immortal cells that go on to make new body and new immortal reproductive cells of a new human being, a cycle that continues forever. For the first time in the history of life on earth, the body cells have evolved a brain that is capable of understanding evolution and capable of deciphering the molecular mechanisms of cellular mortality and immortality. This conscious body is now plotting to take on the legacy of immortality for itself. 

Another pathway is by using hormones.
Can hormones slow ageing? Hormones are your body's chemical messengers. One, called growth hormone (GH), controls bone growth and protein production. GH seems to play a crucial role in ageing: you stop making it somewhere between the ages of 60 and 90. Replacement GH may one day be used to counter some effects of old age, just as some women today use hormone replacement therapy (HRT).
Peter Diamandis competition with Google's Calico will  bring us huge benefits, to talk just about one minor aspect in this race to be forever young. And they have enough money and resources to do it.
Melatonin is slowly reversing the aging process, but if we take it daily we will develop increased tolerance. Ideal it is to take it only 4-5 nights a week, to slow the apparition of the tolerance effect, but we can take it every night without any problems if we want to. Sub-lingual administration is faster, and we can start with 3-5 mg doses, increasing up to 10 mg if we still have sleep problems.
Selective hormone receptor modulators are a hope in sex hormones replacement therapy (estrogens and testosterone) - a crude version of the oriental ways like Tantra-yoga. Or not. We will not know. Yet.

Aggressive supplementation is tested lately. We got 13 essential vitamins, 17 essential minerals and 2 essential fatty acids. Vitamins are divided by water-soluble (C and B), and fat-soluble (A,D,E, and K). The two EFA (essential fatty acids) are alpha linolenic acid and linoleic acid. The more common minerals are calcium, copper, iodine, magnesium, manganese, molybdenum, phosphorus, selenium, chromium and zinc. Of 100 or so minerals naturally occurring in nature only 17 are good for our health. Others are not needed by our body at all and are simply toxins. For each of them we need to learn about EAR - estimated average intake, RDA - recommended dietary allowance, AI - adequate intake, UL - tolerable upper intake level. And the strategy here is that More Is Better. As the last researches point out, a bit more then recommended intake seems to bring marginal benefits. 

My approach to all those different pathways is an economic one, based of the theory of aggregation of marginal gains. To use all the available methods, natural remedies and techniques that will give me  even marginal gains, so in the end the aggregation of all this marginal gains will result in a significant change. 


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