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Reversing hallmarks of rapid aging by silencing a cellular alarm system
Photo credit: Eitan Moses
How the Immune System Rewrites Rapid Aging
One of the difficulties creationists have with presenting the immune system as evidence of intelligent design is explaining why something supposedly designed to protect us so often contributes to our illnesses. A defence system that can turn the body's own damaged DNA into a trigger for further damage is hardly an obvious example of competent, benevolent engineering. It is, however, entirely understandable as a product of evolution: a collection of mechanisms favoured for their benefits, constrained by their history, and carrying costs that natural selection has never eliminated.
Research from the Hebrew University of Jerusalem provides a revealing example. In a paper published in
Genes & Development, Marva Bergman and colleagues investigated how a DNA-sensing protein called cGAS contributes to disorders involving defective DNA repair; the body's response to genetic damage can itself become an important source of harm.
The underlying problem is straightforward. DNA appearing in the fluid surrounding a cell's nucleus can be a warning of infection. cGAS helps detect it and activates an inflammatory defence response. But the DNA need not belong to a virus: damaged cells can expose their own DNA to the same sensor. Consequently, an alarm that normally helps protect against infection can sustain inflammation even when there is no invading organism to fight. The response then risks damaging the very tissues it ordinarily helps defend.
The researchers modelled two human DNA-repair disorders, ataxia-telangiectasia and Bloom syndrome, in turquoise killifish,
Nothobranchius furzeri. In the ataxia-telangiectasia model, disrupting the gene for cGAS partially alleviated reproductive defects, cellular senescence in the liver, and inflammation in the cerebellum. Several measures of genome instability also improved, consistent with cGAS having additional effects inside the nucleus, beyond its familiar inflammatory role.
There was, however, a crucial complication: losing cGAS in fish without the underlying repair defect made pathology and genome instability worse. This was therefore no demonstration that the immune system contains a universally dispensable component, nor a discovery that switching off one gene reverses normal ageing. The same protein could be beneficial or harmful depending on the biological circumstances.
That is precisely where the evolutionary explanation becomes useful. A sensor that responds to DNA in an unusual location offers a broadly effective means of detecting danger, but that signal does not identify the DNA's origin with certainty. Such a system needs safeguards and regulation, and its usefulness does not guarantee that those safeguards will work under every condition. Natural selection can preserve a mechanism whose overall benefits outweigh its costs; it cannot anticipate every future mutation or guarantee freedom from disease.
The study did not test the evolutionary history of cGAS, but its findings illustrate the kind of context-dependent compromise evolution produces. For intelligent-design advocates, the awkward question is why an allegedly perfect designer would make protection and self-inflicted damage so intimately connected. For evolutionary biology, the useful question is how that connection works—and whether understanding it can help us reduce the harm.
This is just one example of how the human body is not a work of perfect design, but the product of sub-optimal compromises constrained by contingent history and lacking in foresight, where additional layers of complexity are not hallmarks of intelligent design that creationists like to imagine, but of the need for controls and compensations for problems created by earlier iterations of the evolutionary cycle. Many more are explained in my book,
The Body Of Evidence: How The Human Body Refutes Intelligent Design