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However, CRISPR-cas9, how revolutionary it may be, is being superseded by even better versions.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
Bringing longevity into the public eye is not an easy thing. There exist many misconceptions about aging, like that aging is way too complex to do something about it, or that aging can at best be slowed down.
Therefore, when bringing up the notion of addressing aging, the following things also often need to be discussed.
1. The notion that aging can be partially reversed. Many people (including MDs and scientists) think that aging at best can be slowed down. Recent studies, however, show that aging can be partially reversed, making old animals younger again. Addressing aging is not just about slowing down aging, but about actually reversing it.
2. Give people a framework. Aging is complex, but it helps if people can boil it down to a few simple rules, like the hallmarks of aging (see for example this seminal paper explaining some hallmarks of aging).
3. Tackling aging scares many people. It conjures up things like overpopulation, the emergence of a biological aristocracy that has the means to rejuvenate itself, and so on. However, it’s important to realize that addressing aging is the best way to address dozens of aging-related diseases at the same time, like heart disease, Alzheimer’s disease, osteoporosis, and so on. Tackling aging is not about immortality (or amortality), but about healthy aging, living longer in the best possible health, tackling dozens of aging-related diseases simultaneously by addressing their root cause, and more.
During my talks, I often ask the audience the following question: “How much longer do you think life expectancy would be if we could cure all heart disease, the most important cause of death in most countries?” The answer: only about 2.8 years longer. This because if people don’t die anymore of heart disease, they will die a few years later of another aging-related disease. Therefore, it’s paramount to tackle aging itself.
4. Address the “I don’t want to become 150 years old if I have to sit in a wheelchair for 70 years” misconception many people have. When people are asked whether they want to live to 150 years, most people will say “no” because they think that they will suffer from frailty and debilitating diseases for many decades. However, if you ask the question: “Do you want to become 150 years old and still look like a thirty-something?”, many more people would want to become that “old”. Recent research shows that it possible, at least in lab animals, to partially reverse aging.
Addressing aging is the best and most powerful way to substantially reduce the risk of dozens of aging-related diseases, and to substantially improve the health of people. By addressing aging, many diseases are tackled at the root cause, instead of just reducing their symptoms (a bit), or just tweaking at some downstream mechanisms of a disease. Addressing aging has the potential to truly impact and change medicine forever.