A Protein That Measures Brain Aging in Humans Also Works Across the Animal Kingdom

A Biomarker Born in Human Neurology

Neurofilament light chain -- NfL for short -- is a structural protein found inside nerve cells. When neurons degenerate, whether from disease or from normal aging, they release NfL into surrounding fluid. Ultrasensitive assays can detect it in blood at very low concentrations, making it a practical window into what is happening in the nervous system without brain imaging or spinal fluid sampling.

In human medicine, NfL has become a standard monitoring tool for diseases like ALS, multiple sclerosis, and Alzheimer's disease, where elevated blood levels indicate ongoing neuronal damage. Researchers have also observed that NfL rises in healthy people as they age, independent of disease, suggesting it tracks gradual neurological changes that accompany aging itself. High NfL in elderly people correlates with increased mortality -- a finding that has prompted speculation about whether the protein could serve as a biological clock, measuring physiological age rather than just calendar age.

Does the Same Pattern Hold in Other Species?

Scientists at the German Center for Neurodegenerative Diseases (DZNE) and the Hertie Institute for Clinical Brain Research at the University of Tubingen asked whether NfL's age-tracking properties were unique to humans or shared across the animal kingdom. The practical motivation was partly veterinary: better tools for estimating biological age and life expectancy in animals would be valuable for wildlife management, zoo medicine, and companion animal care.

The team examined NfL in blood samples from several species in detail and conducted broader sampling across 57 additional species, working in collaboration with Stuttgart Zoo, the Vetsuisse Faculty at the University of Zurich, and a veterinary diagnostics laboratory.

Age-Related Increases in Cats, Dogs, Horses, and Mice

In mice, cats, dogs, and horses -- the four species studied in greatest detail -- NfL levels rose with age in a pattern qualitatively similar to what has been documented in humans. "In neurodegenerative diseases such as Alzheimer's and ALS, NfL is found at elevated levels in the blood. However, the concentration also rises in healthy people with age. We have now observed a very similar age-related increase in mice, cats, dogs, and horses," said Prof. Mathias Jucker, a research group leader at DZNE and HIH.

The most informative data came from mice, where longitudinal tracking was feasible at scale. Forty-four older mice had blood NfL measured repeatedly over four months. The key metric was not the absolute level but the rate of change -- how quickly NfL was rising for each individual. Mice with slowly rising NfL lived comparatively longer. Mice with faster-rising NfL died sooner. "Our data therefore suggest that life expectancy of mice can be estimated from the rate of change of NfL levels -- similar to what has been reported for aging humans," said Dr. Carina Bergman, who led the mouse component of the study.

Broad but Not Universal Across the Animal Tree

Among the 57 additional species sampled, NfL was detected in the blood of all mammals tested. The list spanned rabbits, lions, monkeys, and elephants -- a taxonomically diverse group. Detection was less consistent in reptiles and birds. The protein was found in a crocodile and a parrot, but not all species in those classes. The most likely explanation is that NfL protein sequences diverge enough in some non-mammalian lineages that the antibody-based assay designed for human NfL fails to recognize the equivalent protein.

This is a technical limitation rather than a biological conclusion. Assays calibrated to species-specific NfL sequences might extend the method to reptiles and birds, but that work has not yet been done. The findings were published in PLOS Biology. "Overall, our data show that analysis methods from dementia research are also promising for veterinary medicine, when it comes to assessing the biological age, neurological health, and life expectancy of animals," said Jucker.