Aged Cells Retain Capacity for Rejuvenation via Enhanced Extracellular Support

The study gives a new perspective on the importance of the extracellular matrix (ECM) in the aging process of skin and possibly also in other types of tissue.

The dermal ECM provides strength and resiliency to skin and consists mostly of type I collagen fibrils produced by the fibroblasts. With aging, ECM collagen fragmentation results in reduced fibroblast cell function and in cell shrinkage. In the study, injection of cross-linked hyaluronic acid (a dermal filler that enhances ECM mechanical support and is commonly used to treat aging facial skin) into the buttock skin of 21 individual volunteers about 80 years of age, or into dermal-equivalent cultures, stimulated TGF-β signaling-dependent production of type I collagen and fibroblast elongation. Also observed in vivo were fibroblast proliferation, expanded vasculature, and increased epidermal thickness. Over three months, the fibroblasts showed increased expression of collagen-related genes, produced more collagen, and bound more effectively to the ECM.

“This shows that skin cells in elderly people have the capacity to respond robustly in a very positive way to alterations in the mechanical property of their environment,” said senior author Gary Fisher, PhD and Harry Helfman professor of Molecular Dermatology. “By altering the matrix using an external filler and increasing the internal pressure, we’ve shown that we can essentially trigger a signal for cells to wake up,” said Prof. Fisher. However, he cautions that the new work does not suggest that cosmetic filler should be used throughout the body. Rather, the importance of the discovery lies mainly in the potential to harness the broader understanding of the ECM for prevention and for more effective therapeutic strategies; such as in relating to skin thinning due to aging, for example, which leaves skin more prone to tearing and interferes with healing after incisions or injury.

The study was reported October 25, 2012, in the Journal of Investigative Dermatolology advance online publication.

Related Links:
University of Michigan Medical School, Dept. of Dermatology