Longevity, stress response, and cancer in aging telomerase-deficient mice

Telomere maintenance is thought to play a role in signaling cellular senesc ence; however, a link with organismal aging processes has not been establis hed. The telomerase null mouse provides an opportunity to understand the ef fects associated with critical telomere shortening at the organismal level. We studied a variety of physiological processes in an aging cohort of mTR( -/-) mice. Loss of telomere function did not elicit a full spectrum of clas sical pathophysiological symptoms of aging. However, age-dependent telomere shortening and accompanying genetic instability were associated with short ened life span as well as a reduced capacity to respond to stresses such as wound healing and hematopoietic ablation. In addition, we found an increas ed incidence of spontaneous malignancies. These findings demonstrate a crit ical role for telomere length in the overall fitness, reserve, and well bei ng of the aging organism.