Efforts to slow down the aging process are not just wrinkles. Aging is also the major risk factor for devastating diseases such as cancer, heart disease, Alzheimer's disease and dementia. Going back in time would change medicine forever, and researchers at the Salk Institute believe they have the key.
In an article published this week in the journal Natural Medicine, scientists revealed that a new CRISPR / Cas9 genome editing treatment was able to slow the rapid aging associated with Hickinson-Gilford syndrome in mice laboratory. The rare genetic disorder also affects humans and has no known cure.
"Aging is a complex process in which cells begin to lose their functionality. It is therefore essential for us to find effective ways to study the molecular factors of aging, "said Juan Carlos Izpisua Belmonte, author and senior professor of Salk, in a statement. The progeria, he says, is an "ideal aging model" because it allows for intervention and observing results in a short period of time.
Progeria is caused by a mutation in the LMNA gene. This gene produces the laminate A and laminin C proteins in the cell. But for those with the disease, the LMNA gene creates instead of progerin – a toxic form of Lamin A that builds over time and contributes to the damage associated with aging.
The goal of the scientists was to "disrupt" progerin production with targeted CRISPR / Cas9 therapy.
Cas9 is like a molecular surgeon. The protein is coupled to a synthetic RNA sequence that matches and attracts the defective DNA strand and cuts it (ie gene editing). In this case, Salk researchers used an adeno-associated virus (AAV) – which causes a very weak immune response – to deliver the Cas9 caravan, including with two "guide" RNAs and a "reporter" gene, which lets them know which tissues have been affected by the malfunction of LMNA.
Two months after gene editing, the mice were stronger and about as active as the average healthy mice. They also showed improvements in progeria-specific conditions, including damage to arterial blood vessels and low heart rate. Overall, the lifespan of people treated increased by about 25%.
Given these findings, scientists believe that CRISPR / Cas9 gene modification therapy is very promising for targeting the causes of cell degeneration caused by aging in humans.
"This is the first time a gene modification therapy has been applied to treat progeria syndrome," says Belmonte. "It's an exciting advancement."