Leukocyte function and life span in a murine model of premature immunosenescence

Aging associates with a decline of physiological functions, including the function of the nervous and the immune system. These aged-related changes occur in various degrees in different members of a mouse outbred population. Accordingly, we have proposed a model of premature immunosenescence in mice, based on the demonstration of premature decline in the behavioral response in a simple T-maze and in several immune functions in Swis outbred mice. Those mice with a worst (slow) performance in this test (linked to a higher emotional response to stress) show a shorter life span and a decreased immune function when compared to fast mice. In order to provide biomarkers of 'biological aging' related to health and survival, the present longitudinal study includes the analysis of several immunological parameters such as, proliferative response to mitogen Con A, NK activity and cytokine (TNFalpha, IL-1beta and IL-2) release by peritoneal leukocytes from female Swiss mice. Slow mice showed a lower proliferative response to Con A, IL-2 and IL-1beta release, an impaired NK activity and an increased TNFalpha production as compared to fast mice. Moreover, the age-associated decline of these functions is more strikingly slow than in fast mice. In summary, we propose the above immunological parameters, that change with aging at a different rate in members of a same population, as useful biomarkers to asses the rate of biological aging in mice. (C) 2002 Elsevier Science Inc. All rights reserved.