Andrew P Street
Andrew P Street is a widely published journalist, non-fiction author and former columnist for the Sydney Morning Herald.
There is no area sexier for genetic researchers than ageing, and specifically the fantastic goal of halting the process. However, if you were hoping to defiantly thumb your eternally-youthful nose at death, Paul Nelson and Joanna Masela from the Department of Ecology and Evolutionary Biology at the University of Arizona, US, have some sobering news. You might want to sit down, carefully.
According to their mathematical models ageing isn’t something you can opt out of by better cell health and sci-fi cancer-zapping technologies. It seems that these are not failures of biology that can be mitigated by technology or therapeutic intervention, but a quality fundamental to the way that cells behave. Or to put it another way: thanks a bunch, natural selection.
In a paper published in the journal Proceedings of the National Academy of Sciences, Nelson and Masela show that ageing is inevitable, the result of an “inescapable double bind”.
Ageing can be understood as the accumulation of cellular damage over time. This is because cells suffer from replication errors with each generation, either through protein misfolding, epigenetic factors, or mutation. There’s no way to prevent this deterioration, at least according to the second law of thermodynamics, so multicellular organisms have evolved two primary ways of dealing with it.
One of these relies on intracellular competition, which results in the purging of substandard cells. The other relies on intracellular cooperation, which prioritises the fitness of the whole organism above the fate of individual cells.
The problem is that these strategies are ultimately at odds with one another: competition can favour cells that don’t cooperate; and cooperation can retain damaged ones. Eventually all cells will age and die no matter what path they take, whether cooperating to benefit the organism or competing one on one.
The authors came to their conclusion by modelling these two behaviours over generations. The total output of an individual cell – its vitality – was measured against the proportion of that output devoted to sustaining the multicellular organism. The difference between the two totals – the vigour – marked where it sat on the activity spectrum between full cooperation and full competition.
Cells with low vigour, the researchers found, might be useful to the organism, but could be easily eliminated by competitors. Cells that “decline to invest in traits that are costly to the cell but beneficial to the multicellular organism”, on the other hand, had a competitive advantage.
Cooperation occurs when cells invest in traits which contribute to the greater multicellular good, but are detrimental to the cell itself – and this characteristic is at odds with natural selection, which forces competition, favouring the most vigorous.
But this produces another a problem, since certain low-cooperation, high vigour cells are known by another descriptor: cancer.
The researchers construct equations that show a shifting balance between these two forces, resulting in a bleak outcome, a “double bind of cellular degradation and cancer”.
In theory, there could be a third force that acts against the proliferation of senescence and cancer, but Nelson and Masela found no evidence of one in operation.
Their calculations, they write, give the lie to the argument that ageing “is an accident of imperfect selection where selection fails to purge deleterious, age-related mutations from an otherwise potentially immortal genotype”.
In short, any multicellular organism will eventually succumb to a fate in which cells either die off or multiply uncontrollably. Ultimately, we have a choice between cell degradation or cancer.
“We have shown,” the scientists conclude, “that even if selection against ageing could be made more powerful, ageing would remain an inescapable facet of multicellular life.”
