CRISPR-cas9 is one of the most promising new developments in medicine, and in science in general.
For decades, editing genes was a laborious, difficult and expensive process. It could take many months to years to change just one gene, and it would cost hundreds of thousands of dollars, while requiring a state of the art lab. Presently, with CRISPR-cas9 you can change a gene in less than a day at a cost of around 50 dollars.
However, CRISPR-cas9, how revolutionary it may be, is being superseded by even better versions.
In other words, CRISPR 2.0 has arrived.
This is technology like CRISPR-cpf1, which is a smaller, less complex version of the original CRISPR-cas9 protein. Because of its smaller size, CRISPR-cpf1 is easier to insert into viruses, which can carry it into cells. Another advantage is that CRISPR-cpf1 cuts the DNA in a better way (it creates "sticky ends" instead of "blunt ends").
Another example is DNA base editors. The team of professor David Liu at Harvard University developed an adenine base editor (ABE), which is a hybrid of a cas9 protein and a protein that can edit specific pieces of DNA, called adenines.
Base editors are much more accurate than CRISPR-cas9, and this by a long margin. Contrary to CRISPR-cas9, they create much less double-strand breaks and other (off-target) mutations.
The adenine base editor can change an adenine base into a guanine base, which could fix about half of the 32 000 point mutations that cause disease (point mutations account for about two third of the mutations in the human genome associated with disease - about 32000 out of the 50000 disease-causing mutations).
Besides CRISPR-cas9, also CRISPR-cas13 has been developed, which can modify RNA instead of DNA, opening up a whole new world of possibilities to modify the transcriptome, enabling more fine-tuned control of cells compared to editing the genome (DNA).
The toolbox to manipulate the genome, transcriptome, and epigenome is being extended on a continuous basis, paving the way for the manipulation of cells, and life, in ways never seen before.
We are often being told - especially by sellers of food supplements and skin cremes- that antioxidants slow down the aging process. Antioxidants would delay aging by mopping up reactive free radicals that otherwise damage our DNA. These dreadful free radicals are produced as a side effect by our metabolism.
But mounting evidence shows that antioxidants don’t slow down aging. And the free radicals aren’t always the bad guys. Free radicals can even function as a benign warning sign, revving up the cell’s defense mechanisms, like detoxification enzymes and repair proteins, protecting our cells against age-related damage.
Studies have shown that genetically modified worms that produce more free radicals, live 32% longer. Giving worms a weed-controlling herbicide that creates a surge in free radical production makes these worms even live 58% longer.
While free radicals aren’t always bad, antioxidants can be damaging. A large meta-analysis of 230 000 patients has shown that people who take antioxidants have an increased rate of death.
In conclusion, taking antioxidants isn’t always a good thing. Of course, when you are deficient of certain antioxidants, you do have to take them to replenish the ranks. But taking extra antioxidants to slow down the aging process doesn’t seem to work unfortunately. Meanwhile, aging seems much more complex than just free radicals damaging our cellular machinery.
Author: Kris Verburgh, MD
A Mitochondrial Superoxide Signal Triggers Increased Longevity in Caenorhabditis elegans. Wen Yang, Siegfried Hekimi. PLoS Biology, 2013.
Is the oxidative stress theory of ageing dead? Pérez VI et al. Biochim Biophys Acta, 2009. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. Bjelakovic, G. et al. JAMA, 2007. Picture: cc Wikicommons