“The limit of human life was marked by Jeanne Louise Calment: at 122, this French woman became the longest-lived woman in recorded history.”
This case has opened the door to endless questions: is there a maximum in human life? Which? As technology and medicine advance, there are those who become more ambitious. What if we could break that limit? Is it possible to achieve immortality? Is it really what we want?
Gompertz, Makeham and the limit of longevity
Last summer, a rather curious study on the limit of our mortality was published. In it, the authors explained that when reaching 105 years, the probability of dying reaches its limit in 50%. Before that, it follows a function determined by Benjamin Gompertz and edited by William Makeham in the 19th century.
This function indicates that the probability of mortality doubles every eight years (between 30 and 80). In older people, this ratio drops in what is known as “deceleration of long-lived life”. Moving away from the numbers and their farragosidad, these data arouse an interesting idea: have we reached our top?
Calment reached 122 years, but we do not know if it is the maximum that can be achieved. Many experts, however, believe that this figure is well below the limit we can reach. On the other hand, estimates say that we will live longer, but that does not necessarily mean that this limit shifts.
Studies like the one we mentioned place the limit of our longevity in the 125 years, at most. If this does not change, we will live more and more, but it will be extremely unlikely that we will surpass the French supercentre. What directs our longevity? The secret is in our body, of course.
Why do we age?
Statistical studies are very useful, but it is impossible to talk about aging without going into the complicated world of biology. In order to better understand the intricacies of our body, the opinion of two experts in physiology and genetics will be helpful. Darío Acuña Castroviejo, Phd and Professor of Physiology at the University of Granada, and Arcadi Navarro Cuartiellas, professor and researcher associated with the Catalan Institution of Research and Advanced Studies (ICREA) and specialist in evolutionary genomics.
“We grow old because the capacity of the organism to regenerate the cells is less than the destruction of the same.”
Darío tells us when asked about our body. “As we get older [from the age of 35 or 40, says the doctor], the organism loses cognitive, neural, physical capacities, etc.” This is due to the fact that the organs and tissues reduce their metabolic capacity, and in this way fewer hormones are produced, the cellular energy processes are slowed down, the cells reduce their energy production capacity, since the mitochondria, their power plants, they are falling “.
According to Darío, from the cellular point of view there is a vicious circle:
“The lower the cellular energy, the less the cells have the capacity to perform their functions, including cellular regeneration and repair, it is an old vehicle, worn everywhere, which reduces its efficiency.”
Arcadi gives another point of view, complementary, on our genes:
“We know relatively little when we talk about aging, but much more than we thought, for example, in the genetics of aging, what has been found in human populations are some changes in genome methylation patterns as we get older; in the patterns of splicing, in the protein forms present in our cells, some small genetic variants have been found presumably associated with longevity… “.
“Actually what happens is that there is a huge amount of human diseases that affect longevity”.
Methylation is a process by which a molecule is added in a way that “blocks” that gene, regulating its expression, as if it were a switch. On the other hand, protein splicing is a process by which protein chains are cut and spliced, eliminating or adding amino acids so that the protein becomes active or inactive. It is another control mechanism in the form of a switch.
“Of course, at the molecular and physiological level there is a lot of information,” Arcadi agrees. “There are proteins [like sirtuins] that have to do with aging … But all this being said, in reality what happens is that there is a huge amount of human diseases that affect longevity.”
According to the researcher, we must take into account not only “healthy” aging, but also the relevance of these diseases and risk factors when considering the limits of human life.
What happens to the body when it gets old
“All living species, animals and plants, we have a life cycle that, from the phylogenetic point of view, Darwinian, perfectly fulfills its mission.”
Says Darío, expanding his explanation.
“We have to maintain the species, for which we are born, we grow, we mature sexually, we reproduce, and we die.” The fact of dying soon is important because more years, more mutations accumulate, increasing the probability of transmitting genetic defects to our offspring.”
“Medicine has interfered in this evolution, so we cure diseases, we live many more years than we are entitled to, this is not bad, but it allows gestation at older ages that are often accompanied by gestational risks.”
The doctor goes a little deeper into the changes that occur when our cells begin to age:
“[The most important physiological factors in aging are manifested in] the inability of the stem cells of each tissue and organ to regenerate each of them to keep it young, as well as the epigenetic factors that affect the DNA of these and other cells, that can affect you negatively.”
For Dr. Acuña, oxidative stress is possibly the main mechanism of attrition and cell death that underlies aging.
“Oxygen is vital for us, but it kills us slowly, not everything is perfect and mitochondria, where 95% of the oxygen we breathe is consumed, also generate free radicals that produce oxidative damage in the mitochondria and in the cell.”
“It has powerful antioxidant systems,” he continues. “But, with age, their activity diminishes because they are damaged by their own free radicals, entering that vicious circle of cell damage and aging. We know that slowing down oxidative stress improves mitochondrial and cellular function, and delays aging. The most important thing is not so much to prolong life as to reduce the diseases associated with the passage of time, in other words, to live with a better quality of life.”
And what about our genes?
There is a gene known as cyclin-dependent kinase 2A inhibitor, more also called p16 or CDKN gene that can serve as a great example. “It’s a very relevant gene,” explains Arcadi. “It has been known for a long time that it has a whole series of important effects on senescence in mice.It is also known that with age, this gene is deregulated and expressed at higher levels.” This affects the muscle’s regenerative capacity. mice”.
One of the basic mechanisms of “death” is that the genetic variants that cause problems in old age seem to have had a positive effect on youth.
“If you can down regulate the expression of this gene, and you pass, the mice die of cancer, but if you manage to control it with more precision, what you get is that the mice develop muscle even if they are older.”
Arcadi’s team worked with this gene in humans, identifying its role in various diseases.
“The interesting part of this gene [in humans] is that the genetic variants that protect you from suffering a glioma in childhood, for example, are the same ones that cause a greater incidence in old age.”
It seems that one of the basic mechanisms of “death” is that the genetic variants that cause problems in old age seem to have had a positive effect on youth, “says Arcadi.
“When you analyze the genome from this perspective, you find a whole series of gene variants that seem to meet this pattern.”
“For example, the genetic variants that cause physical degeneration in a natural way,” explains the genetic expert, “wrinkles, diseases, etc., have had a positive effect during our development: they have protected us from certain problems, they have made stronger, more capable of processing certain foods … When you analyze the genome from this perspective, you encounter all kinds of genes that behave in this way, adjusting according to age.”
The team of the Evolutionnary Genomics Lab of Arcadi has worked a lot in this field. “One of the most interesting patterns we find,” the researcher points out, “is that these genes have a greater tendency than the rest of the genome to change, for example, their methylation patterns with age.”
The bulk of our genes, he says, tend to change these patterns, but these, in particular, change significantly. “This is logical, because if a gene has different functions, one way to control it is to change its methylation pattern with place and also with time, obviously the regulation of all this is extremely complicated.”
In search of immortality
What would happen if we could stop, suddenly, aging? There is no omnipotent “switch” capable of paralyzing all the processes that make us grow old, that’s clear. But maybe there are many switches. Could we find the right combination to avoid death?
“The likelihood of finding a solution seems very low,” Arcadi replies to this example. “In the end, what we observe is that the causes of mortality are extremely diverse: one can die from many things and suffer from many kinds of ‘lack of health’ with age, and you can hardly find a solution to all this. It does not mean that you can not find ways and methods to extend life.”
Darío agrees with Arcadi when he explains something more about these possible switches:
“Let’s say that the epigenetic marks of our DNA correspond to our life history, which is thus marked, if we could eliminate all those marks, we would have a young cell, intact, we would almost say virgin to begin again its stage or life cycle.”
“There are very interesting studies being done eliminating some cell marks, rejuvenating the corresponding tissue or organ, perhaps the works in this sense of the scientist Juan Carlos Izpisua, who currently directs the Salk Institute in Los Angeles, United States, are marking an earlier and after aging.”
But if the question already seemed complex, the debate has only just begun.
Do we really want to live forever?
“I do not think that prolonging life is prudent,” Dr. Acuña does not hesitate to reply. “Living 140 years would lead us to overpopulation, lack of global economic resources and, in the end, wars because space is limited, I think that those who say that we are going to live forever, do not have a minimally serious approach.”
From a practical point of view, Arcadi points out another idea:
“There is an explanation, which still needs to be worked on, but which seems quite plausible.” This is the ecological environment of an organism, which determines its extrinsic mortality [ it is not tied to its own nature], it is the one that regulates the optimal age of an organism “.
The question here would be, once this optimal age varies, what evolutionary mechanisms come into play for the organism to be well? This is what we can see in human beings: with the increase in life expectancy new unexpected physiological problems appear.
“There are literally hundreds of laboratories around the world trying to unravel the solution to these problems, there are those who work in sirtuins, there are those who focus on cancer variants, there are those who focus on cognitive, molecular issues …” , confirms, the researcher.
“Yes, we can fight against pathological aging”, continues Darío. “In this sense, great progress is being made although, unfortunately, we still have not managed to eradicate the diseases of the age, we probably have to change many things,” he explains.
“An enormous amount of money is being devoted to studying the genetic alterations of Alzheimer’s and Parkinson’s, to put two epidemiologically significant examples, when only 7% of those diseases are of genetic origin.” For the doctor it is also important to diversify efforts and make other experimental approaches.
Because if we do not end these diseases, in the end, we could be immortal, but the disease would make us suffer for a very long period. That’s not to mention the resources. As we talk about the subject, we live in a world that will hardly be able to withstand the pressure to which we are subjecting it. The question, in short, may not be whether we want to be immortal, but the quality of life we want during our period of existence.
When we have settled that question, who knows, maybe we are much closer to living forever if we wish.