Scientists may have just uncovered a major clue in the quest for immortality by revealing that our lifespan is intrinsically linked to the rate at which our cells undergo genetic mutations. Appearing in the journal Nature, the new study indicates that different species accumulate a remarkably similar number of mutations over their lifetime, and that lifespan is therefore determined by the speed at which these genetic alterations occur.
Humans tend to outlive other mammals such as giraffes, lions, and household pets, and biologists have long speculated that our relative longevity may be mediated by the rate at which somatic mutations occur within our cells. It’s well known that such changes take place in every cell in an organism’s body as it ages, and while many of these genetic alterations are harmless, some can interfere with cellular functioning or even cause cancer.
While it's logical to assume that our likelihood of dying increases as these mutations build up over time, such a hypothesis fails to account for an inconsistency known as Peto’s paradox. If death depends upon the accumulation of somatic mutations, then larger species, which have more cells, should pick up more mutations and therefore have a shorter lifespan.
Yet this simply isn’t the case, as many large animals live longer than smaller species and have surprisingly low rates of cancer. Some scientists have therefore suggested that larger species may have evolved mechanisms to reduce the rate at which somatic mutations occur, thereby extending their lifespan.
To investigate, researchers collected cells from the intestines of 56 individual animals belonging to 16 different species. After analyzing the DNA contained within these cells, they discovered that the number of mutations acquired by each species over its lifetime was roughly the same, despite massive differences in lifespan and body mass.
In other words, all animals end their lives with a similar number of mutations, which means that lifespan is dependent upon the rate at which these genetic changes occur. For instance, the authors discovered that human cells undergo an average of 47 substitution mutations per year, giving us an average lifespan of 83.7 years.
Lions, meanwhile, reach their fatal limit much faster, picking up 160 such mutations per year and living for just 20.6 years. Unfortunately for mice, mutations tend to occur within their cells at a rate of 796 per year, leaving them with just 3.7 years to complete their mortal business.
“To find a similar pattern of genetic changes in animals as different from one another as a mouse and a tiger was surprising,” explained study author Dr Alex Cagan in a statement. “But the most exciting aspect of the study has to be finding that lifespan is inversely proportional to the somatic mutation rate. This suggests that somatic mutations may play a role in ageing."
Intriguingly, however, the researchers failed to solve Peto’s paradox, as no association was observed between body mass and the rate at which somatic mutations accumulate. This is illustrated by the fact that naked mole rats were found to pick up around 93 mutations per year and live for 25 years, while giraffes – which weigh around 23,000 times more than naked mole rats – undergo 99 mutations per year and reach an average age of 24.
“Despite the diverse life histories of the species surveyed—including around 30-fold variation in lifespan and around 40,000-fold variation in body mass—the estimated mutation load per cell at the end of lifespan varied by only around threefold across species,” write the authors.
The mechanisms by which larger animals suppress the rate of mutation in order to extend their lifespan, however, remains a mystery.