Peripheral nervous system aging

The National Institutes of Health Office of the Director awarded The Leland Stanford Junior University $3.324 million under the Trans-NIH Research Support program (CFDA 93.310) on September 30, 2025, to investigate how the peripheral nervous system coordinates organ function during aging and whether targeted interventions can restore organ coordination and function in aging organisms.

The research applies machine learning and spatial transcriptomics to determine age-dependent changes in peripheral nervous system structure and function across diverse organs, examines how environmental stimuli influence peripheral neuron activity and longevity, and tests whether the peripheral nervous system functionally participates in regulating the tempo of aging. The work leverages the recipient's established methods including in vivo aging screens in mice and a new vertebrate model system using African killifish to conduct aging studies at scale.

Performance runs through July 31, 2030, and takes place in Palo Alto, California.

Abstract

Aging alters the function of every organ. An inherent limitation to our understanding of aging is the complexity of the aging process. Thus, fundamental questions remain entirely unanswered: are there mechanisms that coordinate organ function and how do they deteriorate with age? Could such mechanisms be restored to promote longevity? Previous work has revealed how immune cells and blood factors can impact organ aging and orchestrate organ communication. However, IT remains entirely mysterious whether other synchronization systems could regulate organ aging. We are interested in the peripheral nervous system, which connects the brain to all organs, and whether IT could coordinate the tempo of aging. This is a challenging problem because aging is a complex process and organ innervation by the peripheral nervous system is extraordinarily diverse. Our lab has recently generated paradigm-shifting methods to study complex aging biology. We have developed machine learning approaches coupled to spatial transcriptomics to determine the age of multiple cell types and to understand the impact cells have on neighboring cells within an organ. In addition, we have recently developed the first in vivo screens for brain aging in mice. Finally, we have established a new vertebrate model system, the african killifish, to perform aging studies at scale. The time is right to leverage these cutting-edge tools and develop new ones to understand how organ innervation responds to aging and to identify targeted approaches to boost the peripheral nervous system to "RE-set" organ function and coordination during aging. We are interested in the following high-risk, high-reward questions: what are the age- dependent changes in the peripheral nervous system and how do they differ in diverse organs? How is the activity of peripheral neurons influenced by environmental stimuli that impact longevity? Is the peripheral nervous system functionally implicated in organ aging and how does IT coordinate organ aging? Could the tempo of organ aging be "RE-set" by restoring organ innervation? Addressing these questions has the potential to revolutionize how we think about aging and could lead to entirely new strategies to counter aging and diseases. More generally, solutions to this challenge could be broadly applied to other biological phenomena where time and organ coordination are critical.