Efforts to slow down the aging process are just about wrinkles. Getting older is also the leading risk factor for devastating diseases such as cancer, heart disease, Alzheimer's and dementia. Winding back the clock would change medicine forever, and researchers at Salk Institute think they might have the key.
to decelerate the rapid aging associated with Hutchinson-Gilford progeria syndrome in lab mice. The rare genetic disorder also affects humans and has no known cure.
"Aging is a complex process in which cells start to lose their functionality, so it is critical to find effective ways to study the molecular drivers of aging," says senior author and Salk professor Juan Carlos Izpisua Belmonte in a statement. Progeria, he says, is an "ideal aging model" because they are able to intervene and observe results in a short period of time.
Progeria is caused by a mutation of the LMNA gene. This gene produces the lamin A and lamin C proteins in the cell. But for the disease, the LMNA gene instead creates progerin ̵
The scientists' aim was to disrupt progerin production using CRISPR / Cas9 targeted therapy. Cas9 is like a molecular surgeon. The protein is coupled with a synthetic RNA sequence which matches and attracts the malfunctioning DNA strand, and cuts it out (i.e. gene editing). In this case, the Salk researchers used and adeno-associated virus (AAV) – which causes very low immuno-response – to deliver the Cas9 caravan, including with two "guide" RNAs and a "reporter" gene, which lets them know What was affected by the LMNA malfunction?
Two months after gene-editing, the mice were stronger and were about as active as average healthy mice. They also showed improvements among pro-specific conditions, including arterial blood vessel damage and low heart rate. Overall, those treated as life span increase by about 25 percent.
Given these results, scientists believe CRISPR / Cas9 gene editing therapy shows a lot of promise for targeting the causes of cell degeneration caused by aging in humans. ] “This is the first time that editing therapy has been applied to treat progeria syndrome,” says Izpisua Belmonte. “This is an exciting advancement.”