Smoothing the wrinkles in our cells could be a key to reversing aging
Science is often a piecemeal process, with each small, new discovery adding another insight into the mysterious mechanisms behind how our bodies work. A new finding from the University of Virginia School of Medicine adds another piece to the puzzle of how cells in our body degrade with age. The potentially revolutionary breakthrough reveals how our cells can wrinkle with age, resulting in genes not being expressed properly. And the solution could be a novel cellular anti-wrinkle cream, delivered by custom-built viruses.
The research initially found that inside an individual cell's nucleus, the location of our DNA is fundamentally important for it to function correctly. Genes that sit up against the nuclear membrane, the wall that encases the nucleus, tend to remain switched off. However, as we age these membranes tend to become irregular in shape, or wrinkly, and genes that should remain switched off may become over-expressed.
"We have the same DNA in every single cell, but each cell is different," explains Irina Bochkis, one of the scientists working on the project. "So how does that work? Well, actually, certain genes need to be on in the liver and they have to be turned off in the brain, for example, and vice versa. If they're not turned off appropriately, then you have problems."
The study used a model of fatty liver disease to understand this new mechanism. It was found that the condition occurs because with age more normal liver cells turn into fat cells. This cellular transition is triggered by an irregular nuclear membrane releasing DNA that should be switched off.
So what causes this wrinkling of the membrane?
The researchers found that a cellular protein called lamin seemed to be crucial to a cell functioning well. It was observed that a loss of lamin, driven by age, was directly connected to the dysregulation of cellular gene expression that contributed to the development of fatty liver disease. The subsequent hypothesis is that by reintegrating lamin into those cells, the membrane could be smoothed and the cell would function as if it were young again.
The next step to turn this discovery into a viable therapy is to work out a way to deliver loads of lamin to specifically targeted cells. Here Bochkis suggests that engineered viruses could be an ideal delivery mechanism.
Recruiting modified viruses for targeted clinical treatments is a particularly exciting area of research that may have seemed like science fiction just a few short years ago. Today scientists are genetically modifying viruses to be able to travel around our bodies and do everything from kill cancer cells to hunt down antibiotic-resistant bacteria.
The liver is proving to be a particularly effective target for engineered virus-delivery methods. One groundbreaking area of research has seen a virus recruited to deliver gene-regulating proteins directly to myofibroblasts in the liver in the hopes of healing damaged cells in patients suffering from liver fibrosis.
Bochkis suggests her research should be transferable to a broad array of conditions in the body brought on by aging. This wrinkling of the nuclear membrane could be responsible for a variety of age-related diseases, including diabetes and obesity. Of course, the implications of this research are still in a hypothetical stage, but Bochkis is convinced this is a broader metabolic mechanism that could ultimately have a number of applications.
"[If it works] You're going to have normal cells – normal, healthy cells – and they will appropriately express the genes that should be expressed and … you're going to eradicate the stuff that shouldn't be there," says Bochkis. "Every time I give this talk to colleagues, they say, 'Well, do you think this is a universal mechanism?' In my opinion, I think it is."
The research was published in the journal Aging Cell.
Source: University of Virginia