Abstract
Adaptive immune system is in charge of precise defense against a highly diverse array of microorganisms. For defense against new infections, the organism deploys naïve, previously antigen-unexposed, T and B lymphocytes, whose antigen-specific receptors recognize, and eventually orchestrate the removal of, the invading microorganisms. Naïve B, and even more so T, lymphocytes numerically diminish with aging. However, new data suggests that those that remain appear to have maintained their functional potential, contrary to an earlier dogma. These findings refocused our attention upon cell-extrinsic defects in immunity. Results will be presented showing that aging of circulating, most likely soluble, factors, as well as changes in persistent virome, critically modulate both homeostasis and function of the aging immune system. Implications for immune rejuvenation will be discussed.