When I write, my text is populated by misspellings, typos, and an occasional run-on sentence. To eliminate those mistakes, I edit my work. It turns out scientists can do the same thing with genes to extend life.
Researchers at the Salk Institute have developed a CRISPR/Case9 genome editing therapy that suppresses age acceleration.
The regimen was developed to treat Hutchinson-Gilford progeria syndrome, a rare genetic disorder that causes premature, rapid aging. The treatment, developed in experiments with mice, has shed new light on the molecular pathways of aging.
“Aging is a complex process in which cells start to lose their functionality, so it is critical for us to find effective ways to study the molecular drivers of aging,” says Juan Carlos Izpisua Belmonte, a professor in Salk’s Gene Expression Laboratory. “Progeria is an ideal aging model because it allows us to devise an intervention, refine it and test it again quickly.”
Progeria is caused by a mutation of the LMNA gene, which provides instructions for making proteins lamin A and lamin C. These particular proteins support the structure of cells.
“Progeria shifts the production of lamin A to progerin,” according to a report in Science Daily. “Progerin is a shortened, toxic form of lamin A that accumulates with age and is exacerbated in those with progeria.”
Other genes
Studying microscopic roundworms, researcher Cynthia Kenyon published a paper in 1993 that turned the study of longevity upside down. She discovered that the mutation of a single gene, dubbed DAF-2, doubled the life span of the worms.
The DNA sequence of DAF-2 was pieced together in 1997 by a research group led by Gary Ruvkun. They found that the protein coded for DAF-2 closely resembled the receptor protein within humans that respond to the hormone insulin. (Part — 1 of this series noted research on the diabetes drug Metformin and the possibility it may increase the life span of humans.)
Later studies found that DAF-2 controls many other genes turning them on and off, leading many to believe this switch-like effect may regulate proteins that have an impact on life span.
Old dogs — new tricks
In addition to studying the genes of roundworms and mice, researchers are also studying — old people.
Dr. Emily Rogalski, lead author of a 2019 study at Northwestern University’s Superager project, examined the cognitive functions of people 80 + with the mental acuity of people in their 50s. She found that superagers have greater cortex volume and thickness than other people their age.
The cortex is the outer layer of the brain. As we age, it thins and the brain shrinks. Rogalski’s research found that superagers brains shrink more than two times slower than average.
“We didn’t necessarily suspect that SuperAgers’ brains would look more like 50-year-olds than 80-year-olds,” Rogalski, professor of Psychiatry and Behavioral Sciences at Northwestern University’s Feinberg School of Medicine, told The Chicago Council on Science and Technology. “That’s pretty profound, right? To think that you’ve lived 80 years of life, but yet your brain looks like a 50-year-old brain. That’s kind of a dream come true that your brain looks that much younger.”
While Rogalski’s research looked at a variety of factors that separate superagers from the rest of the pack, her study did come across a genetic factor.
Superagers do not have the same kind of MAP2K3 gene as others their age.
The MAP2K3 gene, which is involved in cell growth and function, can produce cell changes called a signaling cascade that result in inflammation and potential neuronal damage in cells found in the brain and spinal cord.
Oxygen treatments
Oxygen therapy, which gives patients more oxygen than they would inhale naturally, has been used in one study to eliminate senescent (aged) cells. Thirty-five subjects over 60 were given treatments in a pressure chamber for 60 days. They showed a decrease in senescent cells and lengthening of telomeres, segments of DNA that shrink with aging.
While research on the use of these therapies and pharmaceuticals to increase human life span has a way to go, the field is growing. New companies are being founded and billions of dollars are being invested.
Many are excited about the future of life expansion. If scientists in the field are successful, we may all have a lot more future to be excited about.
In the final installment, we’ll look at the challenges and ethics of increasing the human life span.