The loss of tissue and organ function with age may depend significantly upon the inability of old cells to divide and/or carry out specialized functions. Like other systems in the body, the immune system deteriorates with age. Because of the interactions between immunologic cells or their products and other cells, this system has been a major focus for aging. Much attention in recent years has been given to possible affect of the immune system in determining senescence. Over the past years, it has become evident that cells within the skin can play an active role in immunologic responses. Since immune function deteriorates with age it is likely that immune function of cells within the skin deteriorates with age, we propose to investigate the effect of age on the immunostimulatory epidermal cell product termed """"""""Epidermal Thymocyte Activating Factor"""""""" (ETAF). (Preliminary studies using newborn human and murine skin versus adult skin suggest that keratinocytes from young donors produce greater amounts of ETAF). Biochemical studies of ETAF will involve identification of ETAF by immunoprecipitation I-l25 labelled ETAF and the previously described antibody absorption technique. A comparison will be made between the protein from young and old donors. If an age related alteration is found we will examine the nature and consequences of this alteration. Using in vivo skin grafts from aged murine donors to young recipients and vice versa, we will determine whether the alteration in ETAF is a primary defect in skin or secondary to aging in other organ systems. We will also assess whether there is an age related altered target organ responsiveness to the effect of ETAF. If ETAF is altered with age, studies will be undertaken to determine if exogenous ETAF can alter aging of skin in vitro as assessed by the Gilchrest model of cultured skin fibroblasts and cultured keratinocytes. We will also examine the effect of ETAF on aging of the immune system using a murine model of allergic contact sensitization. Thus, this study will seek to determine if aging is associated with decreased levels of the immunostimulatory factor ETAF, and if so, we will attempt to determine whether exogenous ETAF can reverse certain age related changes seen in skin and in the immune system.
