Telomerase: A Key to Controlling Aging

A paper in a 1998 Science(1) journal showed that the insertion, into normal aging skin and eye cells, of the gene for hTERT in a form that expresses telomerase continuously, enabled these cells to continue growing and dividing for hundreds of generations without encountering cellular senescence (the phenomenon where cells lose the ability to divide). In effect, these cells stopped aging.

Another paper in a 2000 Experimental Cell Research(2) journal showed that insertion of the telomerase gene into human skin cells, near the end of their replicative lifespan, followed by incorporation of these cells into a reconstituted skin model, resulted in growth of skin cells with increased structural integrity and altered expression levels of numerous senescence related markers, including collagen, to levels indicative of young cells. By most measures we have available, these cells and skin tissue stopped aging and became younger.

And, still another paper in a 2001 EMBO Reports(3) journal compared late-generation telomerase-knockout mice, which had chromosomal fusions and premature aging phenotypes such as bone marrow aplasia, intestinal atrophy and reduced spleen size, with littermates where the telomerase gene had been reintroduced (through cross-breeding), and showed that the latter mice had re-lengthened telomeres, an absence of chromosomal fusions, and an absence of the aforementioned premature aging phenotypes. Taken together, these results strongly suggest that the enzyme telomerase impacts the aging process at all levels, from DNA to cells, tissues, and entire mammalian organisms.

The approach of gene insertion, or transfection, used in the referenced publications is a good proof of principle, but it cannot be used as a therapeutic because there is no available technology for inserting genes into every cell of tissues of the body. Even though such technology is available for inserting genes into individual cells grown in culture, every cell isolate in which the gene is inserted successfully has to be characterized for safety and efficacy individually since gene insertion never occurs at the same place in the genome twice. The inserted gene is also "turned on" at all times unless relatively complex measures are used to provide a way to externally control its expression.

• 1. Bodnar, Ouellette, et al. (1998). Extension of life-span by introduction of telomerase into normal human cells. Science 279(5349): 349-52
• 2. Funk, Wang, et al. (2000). Telomerase expression restores dermal integrity to in vitro-aged fibroblasts in a reconstituted skin model. Exp Cell Res 258(2): 270-8
• 3. Sobol, R. E. and K. J. Scanlon (1995). The Internet book of Gene Therapy: Cancer Therapeutics, http://www.appleton-lange.com/genetherapy. Stamford, Conn., Appleton & Lange.