We have all experienced it closely: someone turns 70 or 75 and begins to see how their ailments multiply suddenly, some chronic disease appears (almost all have to do with age from 60), the entries begin and hospital discharges, with longer and longer hospitalizations , and he died at 85 or 90, leaving behind a gray decade worthy of oblivion. Now, a kinder version of the story, in which scientists studying molecular biologyThey have solid hopes of aging: our protagonist turns 70 and continues to make his life (with more free time, because he has also retired), plays with his grandchildren, does some sports, travels … and blows 80 candles. Dolores? Few, at most, a tooth. And cancer, Alzheimer’s or Parkinson’s don’t look askance. Perhaps, it is true, he moves more awkwardly, but not at all paralyzing, until a stumble at 85 or 90 ends in a bone fracture. A couple of days in bed and he dies: not even the doctor knows the exact cause.
“Well, how centenarians live, although in their case it is due to genetic luck. But, what if the rest could happen to us?” Says Felipe Sierra, promoter of the article (Cell, 2013) in which scientists from all The world defined a starting point to achieve this, with the definition of seven molecular processes that intervene in aging and lay the foundations for geoscience (it fights against diseases associated with age, simply by slowing it down). “It is something that has already been achieved in several animal species, including mammals (mice), with the consequence that they live longer and in better health conditions, “says María Blasco, biologist and director of the National Cancer Research Center (CNIO). It turns out that the story was not science fiction. We reviewed the pillars and the way to mold them.
Molecular damage and stem cells and regeneration: little to scratch
Two of the processes that, at the moment, require less intervention, says Felipe Sierra, director of the Department of Aging Biology at the US Institute on Aging (NIA), integrated into the National Health System (NIH). The first is the molecular accumulation of constant damage to our body, “which we are unable to repair as we turn years.” Exercise, for example, produces it, despite its extremely proven positive effect. “Therefore, I would not advise that it be very intense after the 1970s,” says the doctor in Biochemistry and Molecular Biology. As for stem cells, science studies how to intervene in their regeneration with drugs, based on interesting research (some with a Nobel Prize) thatthey have been able “no longer to delay, but to reverse aging in mice, causing them to remit diseases .” But none are in development yet.
Inflammation: the more than likely ‘boom’ of the senolytics
Turning years, along with bad habits such as smoking, following high-calorie diets or exceeding alcohol, multiplies the appearance of senescent cells, which favor low but constant inflammation, “at the origin of many degenerative diseases, such as fibrosis (pulmonary, renal and liver), atherosclerosis, diabetes and other neurodegeneratives, “says Manuel Serrano, one of the great scholars of the subject, from the Institute for Research in Biomedicine, in Barcelona. Thus, the work is focused on finding drugs that induce the death of these naughty cells , “with very promising therapeutic effects in experimental animals.”
There is already one in the clinical phase, notes Sierra, who does not rule out that it is also possible to intervene in the pillar of inflammation through nutrition, “due to how it alters our microbiome.” For Lorena Enrique Sánchez, member of the clinical nutrition specialization group of the Spanish Academy of Nutrition and Dietetics, and manager of SeaFood Safe Food, these are the dietary guidelines that lower that chronic inflammation that condemns us to age poorly: opting for rich products in omega 3 fatty acids (flax or chia seeds), green leafy vegetables, berries and crucifers (cabbages and broccoli), as well as discard processed foods, flours, refined sugars and excess red meat.
Metabolism: an idyll with intermittent fasting
Optimization of energy by the body, determined by metabolism , should be a goal of those who long for happy aging. For this pillar, drugs such as rapamycin, which is about to hit the market although with another use (“increases the response of those over 65 years of age to the influenza vaccine by 30%,” says Sierra), are Exciting, although they put researchers in an ethical dilemma. “We are looking for drugs that will allow people to be years without getting sick, while weighing 400 kilos and are bedridden in front of the television,” reflects the NIH director. “For me, the ideal would be not to add pills to older people. But let’s be honest:it is unrealistic for today’s society to take on the habits known to slow down aging: eat less, sleep more and exercise, “ adds Ana María Cuervo, co-director of the Einstein Institute for Aging Research in New York. The hardest part of the trident is the caloric restriction, “up to 60% of what is recommended,” notes the researcher, “a cut that has been seen in mice that brings health benefits, although each case would have to be personalized.” José Viñas, Leader of the research group on Aging and Exercise Freshage, of the Faculty of Medicine of the University of Valencia, emphasizes its impossibility: “It is too hard, because it produces tiredness, sexual inhibition, hunger, bad mood … It does not compensate.” However,Raven has something clear:“In the West you eat too much.” And to be energy efficient and therefore age better, you have to swallow less, “because doing it in large quantities fills us with waste.”
Furthermore, the cell biologist continues, “refined sugars are known to be much worse than fats in affecting this pillar.” His colleague Sierra adds that there is another habit at the height of restriction, or even with a higher incidence, intermittent fasting, without the need to reduce calories: “You consume the same as on a normal day, but concentrated in 6 hours, and the next 18, you don’t eat. ” Physical exercise, meanwhile, also helps optimize metabolism, “and its potential to slow aging is equal to that of nutrition,” Viñas asserts, who emphasizes that it is necessary for him to meet these three conditions: to be multi-component (aerobic, anaerobic and short and long-lasting), personalized (“my 90-year-old mother only needs to go up and down stairs; you already me, not “) and social (” if done in company, it is easier to maintain “).
Epigenetics and proteostasis: to continue behaving well
The first pillar designates the changes that occur in DNA that affect gene expression, so influencing it involves playing sports and eating well (for the memory-less, a reminder from the dietitian-nutritionist: “You have to eat fruits and vegetables every day, drink water whenever we are thirsty, reduce saturated fats and change them for unsaturated fats, opt for whole foods, do not neglect protein and increase calcium intake from the age of 51 – they – or 71 – they-)”.
For proteostasis, rest. Cuervo describes it: “It is a kind of quality control, the way cells have to eliminate those that do not meet certain requirements. But that function deteriorates over the years, and is like stopping throwing away the garbage. it is known that Alzheimer’s or Parkinson ‘s is caused by accumulation of imperfect proteins in the brain. the cells are cleaned when you sleep, so the rest intervenes positively in this pillar. the general recommendation is 7 hours of sleep (probably suffice 6, but one is added to cure us in health. However, it varies with the person. The best indicator is how you feel in the morning. ”
Adaptation to stress: a mystery
“With personality we have a problem,” reveals the co-director of the Einstein Institute: “And it is that we work with mice. How is the personality of a mouse measured? The stress we are referring to is cellular, but not psychological. And it’s super important! From the Baltimore Longitudinal Study on Aging, which has collected valuable data for 50 years, it follows that poor people, with more psychological stress, are more likely to get sick than wealthy people. ” Meditation, good humor and optimism, a diet that strengthens the immune system (“lots of vitamin A, such as carrots and yellow and orange fruits and vegetables,” says Lorena Enrique), in addition to exercise, will come to her rescue.
“We are prepared to overcome a convulsive episode, but not to bear the boss pounding us every day. Low-grade chronic stress is what affects aging,” says Viñas. As for the intracellular, which is measurable and has to do with the body’s reaction to external aggressions, the intervention is complex, although drugs such as rapamycin do it. “Based on some clue that slips from the scientific literature: a little stress is good, because it has the cell in a constant state of alert,” Sierra explains, thus charging the popular saying of “what doesn’t kill you , it makes you stronger”.
A wonderful domino effect
“We do not believe that a good state of proteostasis and a very bad state of inflammation are possible,” says Ana María Cuervo. And here is one of the most exciting aspects of these pillars: “They are interconnected, so that if we find a drug with positive effects in one, it is very likely to have them in the rest. There would be no need to intervene in all seven! “ Exclaims Sierra, who trusts the arrival of individualized treatments:” With better markers we will know, through analysis, which pillar to act in each case. “And, of course, this way the old age would be a very different thing.
PHARMACOVIGILANCE, A PENDING ISSUE
The researcher José Viñas, from the University of Valencia, celebrates the apparent prompt arrival (no one dares to give a date) of drugs for aging. However, it warns of a deficiency in the current health system that could detract from its success: the absence of pharmacovigilance. “Biologists who are experts in this area are not taking it into account, but these drugs will only add value if they are accompanied by pharmacological control for the elderly, something that does not happen today. The elderly take many medications. It is not the same to swallow a pill at 40 than at 80, because at this age you take nine more, and all interact with each other. Extending the quality of life goes through a special service that monitors and modulates it. ” After all, the elderly are the great recipient of these drugs, which, in fact, they have been devised in the first instance to treat their illnesses and not so much to prevent them, as is the case of the senolithics. Manuel Serrano, one of its great researchers, speaks: “When we see that they are safe and effective for degenerative diseases, we could consider administering them to healthy people.”