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

**Authors:** Carina Bergmann, Lisa M. Häsler, Marius Lambert, Stephan A. Kaeser, Stephanie A. Schultz, Barbara Riond, Marco Weiss, Martina Balz, Tobias Knauf-Witzens, Mathias Jucker

PMC · DOI: 10.1371/journal.pbio.3003606 · PLOS Biology · 2026-02-19

## TL;DR

The study finds that neurofilament light chain (NfL) in blood increases with age and predicts mortality in humans and several animal species, suggesting it could be a useful aging biomarker across species.

## Contribution

The study demonstrates that NfL is a conserved blood biomarker of aging and mortality across multiple species, including mice, cats, dogs, and horses.

## Key findings

- NfL levels increase with age in mice, cats, dogs, and horses, similar to humans.
- Higher baseline NfL levels correlate with shorter lifespans across 13 species.
- NfL was detected in blood of 39 mammals and some reptiles and birds, indicating evolutionary conservation.

## Abstract

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.

Blood levels of neurofilament light chain (NfL) increase with age in healthy humans and can predict all-cause human mortality, but is this true across species? This study shows that NfL age-related blood levels are comparable across mice, cats, dogs and horses, and may serve as a cross-species biomarker for assessing aging interventions and mortality prediction.

## Linked entities

- **Proteins:** NEFL (neurofilament light chain)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, NEFL (neurofilament light chain) [NCBI Gene 4747] {aka CMT1F, CMT2E, CMTDIG, NF-L, NF68, NFL}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, Nefl (neurofilament, light polypeptide) [NCBI Gene 18039] {aka CMT2E, NF-L, NF68, Nfl}
- **Diseases:** neurodegenerative diseases (MESH:D019636), neural injury (MESH:D014947), Alzheimer (MESH:D000544), GAM (MESH:D004195), neurological disorders (MESH:D009461), death (MESH:D003643), infected wounds (MESH:D014946), neuronal injury (MESH:D009410)
- **Chemicals:** EDTA (MESH:D004492), isoflurane (MESH:D007530), ice (MESH:D007053)
- **Species:** Serpentes (snakes, infraorder) [taxon 8570], Canis lupus familiaris (dog, subspecies) [taxon 9615], Mus musculus (house mouse, species) [taxon 10090], Boa constrictor (boa, species) [taxon 8574], Testudines (anapsid reptiles, order) [taxon 8459], Python regius (ball python, species) [taxon 51751], Chiroptera (bats, order) [taxon 9397], Homo sapiens (human, species) [taxon 9606], Felis catus (cat, species) [taxon 9685], Testudinidae (tortoises, family) [taxon 8487], Bos taurus (bovine, species) [taxon 9913], Equus caballus (domestic horse, species) [taxon 9796], Heterocephalus glaber (naked mole rat, species) [taxon 10181], Gallus gallus (bantam, species) [taxon 9031], Lepidosauria (lepidosaurs, class) [taxon 8504]
- **Cell lines:** C57BL/6J — Mus musculus (Mouse), Transformed cell line (CVCL_C0MW), /6J — Homo sapiens (Human), Cutaneous melanoma, Cancer cell line (CVCL_W797)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12919815/full.md

## References

38 references — full list in the complete paper: https://tomesphere.com/paper/PMC12919815/full.md

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Source: https://tomesphere.com/paper/PMC12919815