Neurofilament light chain may serve as a cross-species blood biomarker to assess aging and predict mortality.

Age-related increases in blood NfL levels comparable to those seen in humans were observed in mice, cats, dogs, and horses.

• The study analyzed NfL in blood of multiple animal species to determine whether the age-NfL relationship observed in humans is conserved across species.
• The pattern of increasing NfL with age was found to be comparable across mice, cats, dogs, and horses relative to human data.
• This finding extends prior human data showing blood NfL increases with age in healthy individuals.

Longitudinal analysis of NfL trajectories in aged mice demonstrated that a faster rate of NfL increase predicts mortality.

• Longitudinal NfL measurements were taken in aged mice to assess trajectory rather than single time-point levels.
• Mice with a faster rate of NfL increase over time had shorter survival, paralleling findings in humans where NfL predicts all-cause mortality.
• This finding mirrors the previously established relationship between NfL levels and all-cause human mortality.

Species with lower baseline NfL levels tended to have longer lifespans when comparing baseline NfL levels across 13 species.

• Baseline NfL levels were compared across 13 different species.
• Species with lower baseline NfL levels tended to have longer lifespans.
• The authors noted that collinearity between body size and lifespan complicates the interpretation of this finding.
• This cross-species comparison suggests a potential link between NfL homeostasis and longevity, though causality cannot be determined due to confounding variables.

NfL was robustly detected in blood of 39 additional mammalian species, as well as a few reptiles and birds.

• Beyond the primary species studied (mice, cats, dogs, horses), NfL was detectable in blood samples from 39 additional mammalian species.
• NfL was also detected in a few reptiles and birds, extending the finding beyond mammals.
• The broad detectability across taxa is consistent with a conserved amino acid sequence of the NfL fragment present in blood.
• This broad phylogenetic detection supports the potential utility of NfL as a cross-species biomarker.

The conserved amino acid sequence of the NfL fragment in blood is consistent with NfL detection across diverse vertebrate species.

• The authors attributed cross-species NfL detectability to a conserved amino acid sequence of the NfL fragment found in blood.
• Conservation of this sequence across mammals, reptiles, and birds enables use of similar detection assays across species.
• This biochemical conservation underpins the proposed utility of NfL as a universal cross-species biomarker.