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1. Ageing is frequently claimed to result in an age-dependent deterioration in immune function. 2. Our results, however, based on 30 known-aged water pythons (Liasis fuscus; age ranging from <1 to 18 years) immunized with keyhole limpet haemocyanin (KLH), demonstrate that age-related changes in immune function may follow different and opposing pathways. 3. Python-specific humoral antibodies (SpAb) showed an age-dependent decrease in cross-reactivity to KLH, whereas natural antibodies (NAbs) ability to bind to this antigen increased with age. 4. Notably, when humoral SpAb and NAb titres were combined, no effect of age was detected in antibody cross-reactivity, strongly suggesting that NAbs may play a crucial role in maintaining immunocompetence during the ageing process.