TGF-β is a problematic protein that is involved in the regulation of chronic inflammation and many other processes important in aging. Unfortunately, presently available means of suppressing TGF-β activity have potentially serious side-effects, as TGF-β has important functional roles in many tissues, even in later life, while it is at the very same time causing a broad set of problems. This is a challenge found in many places in medicine: it is rarely enough to be able to globally increase or diminish the activity of a given protein, as its relationships with the operation of cellular metabolism are usually quite complicated. Here, researchers show that, on top of all of the other issues laid at the feet of TGF-β, it blocks the ability of fibroblasts in aging skin to transform into fat cells and generate antibacterial defenses.
Dermal fibroblasts are specialized cells deep in the skin that generate connective tissue and help the skin recover from injury. Some fibroblasts have the ability to convert into fat cells that reside under the dermis, giving the skin a plump, youthful look and producing a peptide that plays a critical role in fighting infections. Researchers have now discovered the pathway that causes this process to cease as people age.
Don't reach for the donuts. Gaining weight isn't the path to converting dermal fibroblasts into fat cells since obesity also interferes with the ability to fight infections. Instead, a protein that controls many cellular functions, called transforming growth factor beta (TGF-β), stops dermal fibroblasts from converting into fat cells and prevents the cells from producing the antimicrobial peptide cathelicidin, which helps protect against bacterial infections.
"Babies have a lot of this type of fat under the skin, making their skin inherently good at fighting some types of infections. Aged dermal fibroblasts lose this ability and the capacity to form fat under the skin. Skin with a layer of fat under it looks more youthful. When we age, the appearance of the skin has a lot to do with the loss of fat." In mouse models, researchers used chemical blockers to inhibit the TGF-β pathway, causing the skin to revert back to a younger function and allowing dermal fibroblasts to convert into fat cells. Turning off the pathway in mice by genetic techniques had the same result.