Changes in the human thymus during aging.

Although the biological mechanisms of aging are poorly understood, many clinical observations have suggested a close relation between senescence and immunity. Apart from a progressive decrease in muscular power and sensory perception, and loss of cells from most organs and tissues, aging is paralleled by an increasing vulnerability to infections and an increasing liability to malignant tumors and autoimmune conditions. Late-life high-incidence diseases, including vascular disease, maturity-onset diabetes, cancer, amyloidosis, and senile dementia, all exhibit malfunctions of the immune system or are somehow related to the immune system (WALFORD 1980). Speculations and theories about aging and immunity are manifold. Their rationales range from explaining aging by a committed progressive breakdown of functions of immunocompetent cells and their clonal exhaustion (WALFORD 1969; BURNET 1970; HOLLIDAY et al. 1981) to explaining progressive loss of immunity by phenomena of aging such as: (a) somatic mutation (ORGEL 1963, 1973); (b) error in replication or repair of DNA (JOHNSON and STREHLER 1972; HART and SETLOW 1974); (c) error proneness of DNA polymerases and related enzymes (BURNET 1976); or (d) respiration-dependent injury to the mitochondrial genome (FLEMING et al. 1982) in other cells than immunocompetent cells. Several excellent recent reviews have compiled mutual associations between age and immune system of different species, including man (WALFORD 1969; MAKINODAN et al. 1971; KAY and MAKINODAN 1976; MAKINODAN and YUNIS 1977; YUNIS et al. 1978; GOOD et al. 1979; KISHIMOTO and MITSUYA 1980; WILLIAMS et al. 1980; Leech 1980; WEKSLER 1980; MAKINODAN 1980; KAY and MAKINODAN 1981). In particular, T cell system-dependent immune functions seem to decline with age (Table 1), whereas functions of macrophages and B cells do not appear to be impaired (YUNIS et al. 1978; KAY and MAKINODAN 1981; BENNER et al. 1981).