In the subject of sciences that prolong healthy life, the first dimension we need to consider is spatial. A study published in PNAS in November 2015 by Lara M Cassidy et al, was summarized in the BBC and adapted on my twitter and facebook,. Essentially, we all come from a group of humans very much like us, hunters and gatherers, who left Africa through Ethiopia and Somalia, the Horn of Africa. They walked north, towards the Middle East, and east, on the coast of the Red Sea, then the Indian Ocean, all the way to southeast Asia, the south of China, the islands of Indonesia, and gave origin to the aborigines of the Pacific and Austrália.

Those who had gone to the Middle East went around the Mediterranean, went up to Europe and got stuck, as all was frozen north of the Alps. They veered east to central Asia through the steppes south and north of the Black and Caspian seas, all the way to the Baikal sea. Those who took the southern route probably mixed up with those who travelled over the southern steppes. Those who took the northern steppes to the Baikal region rapidly crossed to the Americas over the ice bridge. I have been personally with investigator eyes at the Himalaya, the Andes and the Mexican Cordillera. The physical and cultural similarity of these peoples is impressive.

The next dimension to consider in the sciences that prolong healthy life is temporal. It is well established that Homo sapiens appeared some 100 thousand years ago west or south of the paradisiac central African region of mountains and lakes that gives origins to its major rivers. It may have been in present day Ethiopia, in the Rift Valley, or northern South Africa.  A small group, a few hundred people, crossed the Horn of Africa 60 thousand years ago; there were people well established in the Baikal region 15 thousand years ago, and between 15000 and 5000 in the Americas. In central Europe the timing was 7500 years ago.

The third dimension is within the Europeans, who and how these people are. Irish studies are interesting because to get there people have to cross the whole European continent. It is somewhat like nowadays, the young never stop, keep on walking, until they develop a family, find a confortable site and develop agriculture. Evidence shows that there, at the tip of the North Atlantic, there were people similar to the natives of Sardegna and Spain 5200 years ago; 4000 years ago there was s strong slavic component of ukrainian origin.

Other evidence shows that the original european population of 7500 years ago was made of strong hunters with dark skin and blue eyes, a type that does not exist any more, except perhaps in the north of Spain. This somehow diluted into the kind that came later from the Middle East, well-versed in agriculture, already with fair skin, brown eyes and dark hair. Besides the slavs, there is a genetic contribution of a third siberian group, mysterious because these analyses are carried out in a few pieces of bone. It shows a double asiatic influence. The first when the continent was settled, bewteen 15000 and 7500 years ago. Not before because of the Ice Age, as there were a few humans roaming about since 60 thousand years ago. Later, there was a staged second wave.

There is no doubt that healthspan and lifespan increase together in studies when they are considered in studies about what may prolong healthy life, and that they are genetically related. It is also relatively clear that the skin of Europeans became fair in order to facilitate vitamin D metabolism, and that slavs brought with them the possibility of lactose digestion into adult age. Metformin, a drug used to lower sugar in diabetics, prolongs the life of laboratory mice, slows their aging and development of cancer. Hunger, fasting and prolonged caloric restriction slows aging and development of cancer in rodents, as well as the deterioration in the state of their memory and muscles, as well as onset of cataracts.

The next issue thay mey be important in the consideration of what may matter to prolong healthy life is the relevance of disease and death. The cascade of death is hard to establish in each case, even more so when genetics and external causes such as trauma need to be accounted for. It is usual to think that age brings disease, and, old cells and sick cells do look alike in a molecular manner.  Old rats and old humans do not take well deviations of the normal such as heart arrests, delirium, mitochondrial dysfunction, DNA damage, bad intercellular communication or inflammation. But it may be useful to consider the opposite of this simple and intuitive model: it may be that diseases speed up aging. Metabolic syndrome is associated with renal failure and cognitive dysfunction, periodontal disease and skin inflammation. Chronic obstructive pulmonary disease is associated with with renal, muscular and cognitive deterioration.  HIV and its treatment are associated with physical, cognitive, vascular and bone decline. So, age accelerates diseases that accelerate aging. Some medications, such as beta-blockers and AAS, modify this double vicious circle, and they have been known to physicians for a while.

Lifespan has been used to demonstrate the effect of resveratrol, present in red wine and grape and a few other fruit juices, which prolongs life of yeast, nematodes and flies. In mice it reverts the so called French paradox, that is, the development of insulin resistance, obesity and dyslipdemia on a high-fat diet. Rapamycin increases lifespan, decreases aging and risk of disease, including psychiatric disorder, c ardiac failure and obesity. Metformin may function as a hunger mimetic, and it is being investigated as prevention for cancer and cardiovascular disease, in the absence of diabetes.

As research continues on what prolongs healthy life, it will be critical to consider which interventions pause life, delay death, or really interfere with the mechanism of aging itself. One of the challenges is to find new mechanisms beyond mutations eat-2 or eat-18, for exemple, through which nematodes prolong life with caloric restriction. Other interventions reduce apetitte or make food unpalatable. As the authors I have based much of the medical side of my paper say: “Upstream mechanistic research would end up focusing on appetite and food intake control, rather than on pathways of cell dysfunction and health. Well-planned studies address this caveat by measuring food consumption and body weight. Thus, seemingly novel processes or mechanisms identified in lifespan studies may simply point to known interventions”. (J. O. Brett and T. A. Rando. Curr Opin Genet Dev. June 2014).

The final impression is that people should strive to accept more deeply their own genetic profile, and this nutritional adaptation will benefit them as much as other environmental adaptations, as dark skin became fair. Surely it is these mechanisms of adaptation that prolonged human life and health so markedly as it appears in the research studies. It is to their own origins that people need to look, perhaps helped by experts, while the research suggested by the neurologists from Stanford does not produce radical genetic change.

Prof. Dr. Paulo Rogério Mudrovitsch de Bittencourt, PhD, FAAN


 

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