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Blood levels of neurofilament light chain (NfL) increase with age in healthy humans and have been shown to predict all-cause human mortality. To determine whether this relationship is conserved across species, we analyzed NfL in the blood of various animals. We observed age-related increases in NfL levels comparable to those seen in humans in mice, cats, dogs and horses. Longitudinal analysis of NfL trajectories in aged mice demonstrated that a faster rate of NfL increase predicts mortality. When comparing baseline NfL levels across 13 species, we found that those with lower baseline NfL levels tended to have longer lifespans; however, the collinearity between body size and life span complicates the interpretation of this finding. NfL was also robustly detected in blood of 39 additional mammalian species, as well as a few reptiles and birds, consistent with a conserved amino acid sequence of the NfL fragment in blood. Given the growing interest in NfL as a biomarker for neurological health and mortality in humans, our findings suggest that NfL may serve as a cross-species blood biomarker for assessing aging interventions and predicting mortality.