Telomerase reverses aging in skin model

Scientists from Geron Corp. (Menlo Park, CA), Xgene Corp. (Burlingame, CA), and Stanford University School of Medicine report that the telomerase gene restores the ability of aging human fibroblasts to form normal skin structures in a model of tissue formation. Published in the journal Experimental Cell Research (ref. 1), the research shows that the proliferative capacity and expression profiles of senescent cells that have incorporated telomerase resembles young skin cells.

Skin is composed of keratinocytes, which form the upper epidermal layer, and fibroblasts, which form the underlying dermal structures. These layers are connected by a tight junctional membrane. Fibroblasts aged in vitro lose the ability to form junctions with young human keratinocytes when the two cells were put into a mouse model of tissue formation. This condition occurs in the elderly as increased skin frailty and subepidermal blistering.

In the study, introducing telomerase to aging fibroblasts increased their proliferative capacity and restored their ability to reconstitute normal human skin structures in the model system. In addition, microarray analysis showed that senescent fibroblasts with added telomerase displayed expression patterns that resembled younger fibroblasts. Specifically, genes normally down-regulated in aging fibroblasts, like collagen I and III, were expressed, while several markers associated with the destruction of dermal matrix and inflammatory processes, normally over-expressed in aging tissue, were repressed. Telomerase, therefore, not only confers replicative immortality to skin fibroblasts, but also prevents or reverses the loss of biological function associated with aging cells.

"This is the first demonstration of a beneficial effect of telomerase activation in human cells in an in vivo animal model," stated Calvin Harley, Geron's chief scientific officer. "The research brings the company one step closer to a telomerase gene therapy for the treatment of chronic degenerative diseases in the elderly, including debilitating skin ulcers."

"Demonstrating that telomerase restores a youthful function to aging human cells in an animal model supports our belief that this technology can be developed for regenerative medicine," noted Thomas Okarma, Geron's CEO. "We have multiple opportunities for the treatment of disease in which telomerase can be incorporated into cell and gene therapies. Chronic skin ulcers and liver diseases are two applications among others that we are actively pursuing."

Geron is a biopharmaceutical company focused on discovering, developing, and commercializing therapeutic and diagnostic products for applications in oncology, research tools for drug discovery, and regenerative medicine. Geron's product development programs are based upon three patented core technologies: telomerase, human pluripotent stem cells, and nuclear transfer.

Reference: Walter D. Funk, C. Kathy Wang, Dawne N. Shelton, Calvin B. Harley, Garrett D. Pagon, Warren K. Hoeffler, "Telomerase expression restores dermal integrity to in vitro-aged fibroblasts in a reconstituted skin model," Experimental Cell Research, 2000 Aug 1;258(2):270-8.

For more information: Calvin B. Harley, Geron Corp., 230 Constitution Dr., Menlo Park, CA 94025. Tel: 650-473-7700 or 800-782-3279. Fax: 650-473-7701.

Edited by Laura DeFrancesco
Managing Editor, Bioresearch Online
Email: ldefrancesco@bioresearchonline.com

Source: Geron Corp.