How much does genetics weigh on longevity? In other words: is it our genes that determine how long we will live? For decades, the scientific community has debated this question, with studies attributing to DNA a modest influence, estimated at between 6% and 25%. Now, however, a rigorous new study conducted by an international group of scientists and published in Science suggests that these estimates are too low. Once the data are corrected, it emerges that the heritability of intrinsic human lifespan would be about 50-55%, a value in line with other complex physiological traits.
Heritability and mortality from accidental causes
To understand this discovery, we need to distinguish between two types of mortality:
- Extrinsic Mortality: Deaths caused by factors external to the body, such as accidents, homicides or infectious diseases.
- Intrinsic Mortality: Deaths resulting from internal biological processes, such as cellular decline and age-related degenerative diseases.
Heritability is a statistical measure that indicates how much of the variation in a trait (in this case, longevity) in a given population is due to genetic differences. The problem with previous studies, the authors write, is that they were often based on historical cohorts (18th and 19th centuries) with high rates of extrinsic mortality. According to the researchers, extrinsic mortality acts as a confounding factor that masks the genetic signal, artificially lowering the impact of genetics.
Let us imagine we have two identical clocks, built with exactly the same material and the same mechanism (just as identical twins have the same DNA).
If we put both clocks in a protected room, they will stop almost at the same time because of the natural wear of their internal gears. In this case, it is clear that their “lifespan” depends on the quality of the parts with which they were built (their genetics).
Now let us imagine putting the same clocks in a crowded square. One is crushed by a car after two days, while the other keeps ticking for ten years until a brick falls and destroys it. If we looked only at the data on when they stopped, we might wrongly conclude that the way they were built (genetics) does not matter at all, since one lasted very little and the other a long time.
Mathematical models and twin studies
Hence the insight. Analyzing the data of three large twin databases (Danish, Swedish and the SATSA study) and of the siblings of US centenarians, the researchers applied Falconer’s formula, which compares the correlation of lifespan between monozygotic (MZ) twins, who share 100% of their genome, and dizygotic (DZ) twins, who share about 50% of it, and used advanced mathematical models to separate the intrinsic and extrinsic components of mortality.
“DNA, half of longevity”
Here are the results:
- Estimates doubled: As anticipated, when extrinsic mortality is removed from the calculations, the heritability of longevity rises from the common 20-25% to about 55%.
- Historical validation: In the SATSA study, the researchers observed that measured heritability naturally increases over the decades (from 1900 to 1935), as extrinsic mortality in society decreased thanks to medical and social progress.
- The Effect of cutoff age: The research also clarifies how the minimum age for inclusion in a study (cutoff age) influences the results. In modern populations with low extrinsic mortality, including early deaths is fundamental to capture the genetic signals of intrinsic mortality.
Il metodo SoLongevity Clinic
Why is this research important?
These conclusions are surprising because they align the heritability of human longevity with that observed in other species, such as laboratory mice, and with most other human physiological traits.
This study strengthens the rationale behind large-scale efforts to identify genetic variants associated with longevity and to link these differences to specific biological pathways that regulate aging. If genetics explains half of the variation in our “biological” lifespan, identifying the genes involved could revolutionize preventive medicine and public health.
A note of caution
Although the genetic component is stronger than thought, 50% of the variation remains unexplained. This “missing” part is attributable to environmental influences (lifestyle, socioeconomic factors), to biological stochasticity intrinsic to the organism (even if two cells have the same DNA and are in the same environment, they can react slightly differently) and to epigenetic modifications (which influence gene expression). Genetics, in short, is not a destiny already written, but a fundamental foundation that we now know to be much more relevant than science had previously assumed.
The discovery makes the interventions that can be implemented today to enhance positive genetic traits and limit negative ones even more important. This is the goal and philosophy of the SoLongevity method and of the SoLongevity Clinic in Milan.
A study that changes the paradigm
“For those who work in longevity medicine, these results are a radical paradigm shift — comments Alberto Beretta, President and Scientific Director of SoLongevity —. While on the one hand it is true and scientifically established that lifestyle and the environment — the so-called exposome — in which we live are decisive, on the other hand we cannot imagine practicing longevity medicine without periodically updating our knowledge of the genes that determine it.
And here I would like to clarify a fundamental concept. The ‘genetics of longevity’ — or, if you want to reverse the concept, the ‘genetics of mortality’ — is the result of the combination of two different categories of genes: those that control the intrinsic mechanisms of biological aging (the famous hallmarks of aging) and those that control the way and timing in which human beings develop age-related diseases.
On the former we still have partial knowledge, focused on 3 or 4 apparently dominant genes that are still difficult to interpret in clinical practice. Studies on centenarians will guide us in this field. On the latter, instead, we have data available on thousands of genes which, analyzed as a whole, provide us with very useful information for stratifying a person’s specific risk of developing a certain disease.
When we manage to integrate these two types of genetic information, we will finally be able to understand why 50% and not 5% of aging is determined by genetics. It seems difficult but, with the arrival of artificial intelligence, the goal is now within our reach”.
