Aging and injury drive neuronal senescence in the dorsal root ganglia

Aging negatively impacts central nervous system function; however, there is limited information about the cellular impact of aging on peripheral nervous system function. Importantly, injury to vulnerable peripheral axons of dorsal root ganglion (DRG) neurons results in somatosensory dysfunction, such as pain, at higher rates in aged individuals. Cellular senescence is common to both aging and injury and contributes to the aged pro-inflammatory environment. We discovered DRG neuron senescence in the context of aging and pain-inducing peripheral nerve injury in young (~3mo) and aged (~24mo) male and female mice. Senescent neurons were dynamic and heterogeneous in their expression of multiple senescence markers, including pro-inflammatory factor, IL6. Senescence marker-expressing neurons had nociceptor-like profiles, included high-firing phenotypes, and displayed increased excitability following IL6 application. Furthermore, elimination of senescent cells resulted in improvement of nocicep..., Animals
All animal procedures were approved by the Stanford University Administrative Panel on Laboratory Animal Care and Institutional Animal Care and Use Committee (IACUC; 34760) in accordance with American Veterinary Medical Association guidelines and the International Association for the Study of Pain. All mice were housed 2-5 per cage, maintained on a 12-hour light/dark cycle in a temperature-controlled environment (Temp:68-74°F; Humidity:30-70%) with ad libitum access to food and water. Young male and female mice used were 11-16 weeks old, wild-type C57BL/6J mice (Jax stock #00664). Aged male and female mice used were 20-24 months old, wild-type C57BL/6JN mice (NIA aged rodent colony). We did not note any sex differences in the expression of senescence markers and therefore combined male and female DRG throughout all analyses. Aged mice were pre-screened for abnormal masses and cataracts and were included in the study only if they appeared healthy.
Human samples
Use of human post-..., , # Aging and injury drive neuronal senescence in the dorsal root ganglia

Dataset DOI: [10.5061/dryad.fbg79cp5v](https://doi.org/10.5061/dryad.fbg79cp5v)

## Description of the data and file structure

Data includes individual data points generated from multiple independent experiments published at: 

PMID: 40369367  
PMCID: [PMC12081305](https://pmc.ncbi.nlm.nih.gov/articles/PMC12081305/)DOI: [10.1038/s41593-025-01954-x](https://doi.org/10.1038/s41593-025-01954-x)

### Files and variables

**File: Donovan_SourceData_ED_Fig1-6.xlsx**

**Description:** File contains raw data generated in Figures 1 through 6 of the extended data file (DOI: [10.1038/s41593-025-01954-x]).(https://doi.org/10.1038/s41593-025-01954-x) Data are separated into Excel file tabs.

**Variables**

Tab titled \"Figure 1\" 

a)      Histological analysis- SA-β-galactosidase activity assay using young and aged mouse DRG tissue. Displayed as %positive pixels/area (μm).

b)     Generated fluorescence images representative of..., Data has been de-identified by only providing age, sex and cause of death. All samples are post-mortem and patients were registered organ donors consented prior to death.