Finch and Crimmins proposed that the reduction in lifetime exposure to infectious diseases and other sources of inflammation has made an important contribution to the historical decline in old-age mortality (Finch and Crimmins, 2004). This will likely also be true in zebrafish, because one of the most critical problems in their husbandry late in life derives from multiple microbial infections. Resistance to microbial infectious diseases obviously declines with age in adult zebrafish. The cellular components involved in defense against pathogens/ microbial agents are beyond the scope of this article. However, it should be noted that zebrafish have an almost complete set of the Toll-like receptors (TLRs) (Jault et al., 2004; Meijer et al., 2004). The TLR family is an evolutionarily conserved component of the innate immune system that responds to specific pathogen-associated molecular patterns (Takeda et al., 2003), and important lines of evidence indicate that the innate immune system in zebrafish can be the primary layer of defense against microbial pathogens. Rag-1-deficient zebrafish that lack adaptive immunity have normal life expectancy in regular fish water, which notoriously contains multiple pathogens (Wienholds et al., 2002). Importantly, adult zebrafish have a strikingly high expression of TLRs in the skin (Jault et al., 2004), which may be highly relevant to their primary mechanism of defense against pathogens by the innate immune system. Aged adult zebrafish are naturally more susceptible to tuberculosis caused by Mycobacterium marinum, where TLRs and innate immunity play prominent roles of defense. This implies that age-dependent functional declines of the innate immune system including the TLRs expression levels are crucial for infectious diseases followed by inflammations late in life of zebrafish. However, zebrafish aging-associated immunity has not been investigated so far in detail. Due to declines of both innate and adaptive immune functions with age, leading to increased susceptibility to infectious diseases and cancer in vertebrate animals, importance of the immune system in aging zebrafish needs to be recognized and immunological senescence should adequately be studied with respect to various age-dependent diseases.
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