The longest-lived person for whom a reliable record is available was Jean Calment, who lived 122 years and 164 days. Although for most of us the passage through this world will be much more ephemeral, the age of this French woman today marks, awaiting a new record, the maximum potential longevity of our species.
Now, here it is convenient to differentiate two aspects. It is one thing how many years we are going to live and quite another how many it will have been worth living for to enjoy good health and quality of life. In recent decades the increase in life expectancy has been greater than the increase in healthy life expectancy and we cannot be overly optimistic. Let’s start by finding out if human life has natural limits today that we can significantly exceed in the future. And if so, let’s identify what strategies we could use to achieve that goal. The biology of aging in the animal kingdom offers us interesting clues in this regard.
Aging in nature
The oldest mammal is the Greenland whale ( Balaena mysticetus ). The genome of this gigantic cetacean, whose longevity record stands at 211 years, shows various adaptations to avoid diseases associated with advanced age. In particular, cancer.
Something similar occurs with the African hairless mole rat ( Heterocephalus glaber ), which can exceed thirty years of life. This is almost eight times more than expected in such a small rodent. Such rats, with highly elaborate social habits, avoid exposure to ultraviolet rays by living in galleries. In addition, they show high concentrations of a high molecular mass variant of hyaluronic acid in their tissues. This allows your skin to be very flexible (a necessity when wandering through galleries) and, as a side effect, provides great resistance to cancer and prevents sarcopenia (atrophy and loss of muscle mass) with age.
A third example is Brandt’s bat ( Myotis brandtii ), which despite its tiny size (between 4 and 8 grams) lives for more than 40 years. The secret here lies in hibernation, which results in a low metabolic rate (we will see its advantages later). But also in a mutation in the genetic sequence of growth hormone receptors, which produces dwarfism and increases longevity.
Finally, the oldest vertebrate is the boreal shark ( Somniosus microcephalus ). This species exceeds five meters in length, growing as an adult at a rate of only one centimeter per year. Therefore, the life span of the largest specimens could exceed five centuries, as suggested by carbon fourteen dating of the nucleus of the lens of their eyes.
Various species of invertebrate animals also have very long lives and also do not develop obvious signs of aging. Therefore, their adaptations could serve as a model not only to live longer, but to delay senescence. This is the case of the American lobster (Homarus americanus), whose extreme longevity (exceeding 100 years) and continuous growth are associated with high telomerase production. That is, the enzyme responsible for repairing errors in DNA. And that allows you to indefinitely prolong cell proliferation.
Another example is found in the Icelandic clam ( Arctica islandica ). One specimen reached 507 years, as revealed by its growth rings (dendrochronology). The key to their longevity is a very low metabolic rate, so they release fewer free radicals that oxidize cell membranes, combined with a great resistance of their mitochondria to the effects of oxidative stress. Also, the telomeres (ends) of your chromosomes do not seem to shorten with age.
Aging and Longevity: Are They Necessarily Two Sides of the Same Coin?
Various tools are currently being considered to slow down, and even reverse, aging. These include gene editing therapies, such as those based on the CRISPR / Cas9 technique, which could eliminate undesirable genes. For example, those responsible for certain types of cancer or inherited diseases caused by small mutations, such as cystic fibrosis.
Similarly, nanotechnology could help us by designing cell-scale nanorobots that would circulate through the bloodstream, eliminating atheromas or incipient tumors (thrombolyzing nearby blood vessels). Now, the problem is that, even being able to end cancer, cardiovascular diseases or those derived from diabetes, the three main causes of death today, our lives would only last 15 years. This is due to immunosenescence, which determines that the majority of deaths in the elderly are due to viral and bacterial infections that do not usually pose a risk to young people.
Something similar occurs with other approaches. For example, reducing exposure to oxidative stress by limiting caloric intake (that is, restricting the amount and energy value of foods to achieve an optimal diet) has effects on SIRT1. This deacetylase enzyme is involved in the intracellular regulation of the response to stress and other homeostatic factors (such as insulin resistance), increasing the longevity of mice by up to 50% (on the contrary, obesity reduces it by half). Similar effects have been achieved with a natural compound, resveratrol, which increases the expression of this protein.
In our case, the longevity increase is less than in mice, around only 5%, but populations that practice caloric restriction, such as on the Japanese island of Okinawa, remain in good health for longer and have more chances of reaching centenarians. Their diet is 90% carbohydrate and their rates of heart disease, cancer, diabetes, and senile dementia are lower than in other populations.
Likewise, it has been proven that increasing the levels of the coenzyme NAD +, involved in oxidation-reduction reactions, makes it possible to reverse muscle degeneration associated with aging in mice.
All of this is crucial today, because by delaying senescence the duration of the final stage of life with greater dependency, the so-called “fourth age”, would be shortened, alleviating the enormous economic and social health cost it entails for society.
The search for immortality
Based on the foregoing, the search for strategies to radically prolong human life will have to run in other directions. One possible way would be to investigate the mechanisms that allow flying animals, like most birds and bats, to live much longer than terrestrial animals, despite having a much higher metabolic rate, despite having a much higher metabolic rate (the rest mammals and some flightless birds).
Thus, although longevity is inversely related to metabolic rate per unit mass, a sparrow ( Passer domesticus ) can reach 23 years. This occurs despite expending a lot of energy on the flight, endogenously generating a high amount of free radicals from its oxidative metabolism. On the other hand, a house mouse ( Mus musculus ), whose metabolic rate is considerably lower, does not exceed four years of life.
The answer to this paradox is that evolution has endowed flying animals with more effective mechanisms to combat the effects of oxidative stress. This is explained by the classical hypothesis of Sir Peter Medawar, who indicated that natural selection acts only on those genes that manifest their effects before organisms die.
In the case of flying animals, the flight helped them minimize the risk of predation, giving them a longer life expectancy a priori. This made it worthwhile to invest in the repair mechanisms of cellular damage that derives from oxidative metabolism, a factor that is ultimately behind aging. On the other hand, investing in mechanisms that help prolong the life of a mouse, when the probability that it will be alive in the wild after a few years is practically nil, would certainly have been a bad investment.
Therefore, biogerontologists would do well to focus their efforts on the search for the specific mechanisms on which natural selection acted in flying organisms, allowing them to develop a longer life.
Paul Palmqvist Barrena (Professor of Paleontology, University of Malaga)
This article was originally published on The Conversation. Read the original.
