Age-related biochemical profiling reveals multi-system physiological decline in the annual fish Nothobranchius...

Annual killifishes of the genus Nothobranchius compress a vertebrate life cycle into a few months, which is what makes them useful in aging research, yet no broad biochemical description of ageing exists for N. guentheri. In a cross-sectional design, we measured 27 clinical chemistry analytes in whole-body homogenates of male and female fish sampled at 3, 6 and 9 months of age (20 analytical samples). Age trends were assessed by Spearman rank correlation, and age, sex and their interaction by two-way ANOVA. Twenty-four of the 27 analytes fell with age. Calcium declined most steeply (r = - 0.573, p = 0.008), followed by fructose (r = - 0.507, p = 0.023), albumin (r = - 0.486, p = 0.030) and magnesium (r = - 0.479, p = 0.033); potassium fell just short of significance (r = - 0.422, p = 0.064). Only adenosine deaminase, C-reactive protein and HDL cholesterol trended upward, none of them significantly. Males had higher creatinine, carbon dioxide and HDL cholesterol than females. The picture is one of generalised decline rather than the selective elevations of glucose, lipids and nitrogenous waste seen in long-lived mammals, and is most simply read as progressive loss of metabolically active tissue. We suggest, as a hypothesis for testing, that the abrupt terminal mortality familiar to killifish keepers follows the crossing of a threshold after months of subclinical decline. Sample sizes were small and p-values uncorrected, so individual associations need confirmation, but the panel offers endpoints that can be read out within one generation of this species.