Aging is a significant risk factor for cardiovascular diseases, including hypertension and heart failure. Previous studies in our laboratory have demonstrated that in aging, senescent glial cells accumulate in the key brainstem region regulating cardiovascular function, such as the rostral ventrolateral medulla (RVLM). Senescent glial cells are known to secrete senescence-associated secretory phenotype (SASP) factors causing neuroinflammation, which could lead to sympathoexcitation. While elevated sympathetic nerve activity (SNA) has been implicated in neurogenic hypertension in obesity, its relevance to age-related blood pressure increase is not clear. Hence, we hypothesized that aging contributes to increases in blood pressure mediated through increase in sympathetic nerve activity. To address this hypothesis, young (3 months, n=4) and aged C57BL/6J male mice (18-24 months, n=4) on regular chow diet were surgically implanted with radiotelemetric devices in their carotid artery for continuous monitoring of blood pressure and heart rate. After seven days of recovery period, blood pressure and heart rate data were collected from conscious, unrestrained mice on a normal chow diet continuously for a period of 48 hrs. Data were analyzed by unpaired student’s t-test and expressed as mean ± S.E. Aged mice exhibited higher systolic blood pressure (SBP) (127.3 ± 2.29 vs 106.21 ± 4.17 mmHg, p < 0.005), diastolic blood pressure (DBP) (98.23 ± 4.23 vs 84.53 ± 2.65 mmHg, p < 0.05), and mean arterial pressure (MAP) (112.81 ± 2.97 vs 95.39 ± 3.09 mmHg, p < 0.01), compared to the young mice. To assess SNA, mice were administered intraperitoneally with ganglionic blocker, hexamethonium and changes in mean arterial pressure (MAP) were recorded. Aged mice displayed a greater depressor response (-47.10 ± 2.59 vs -12.09 ± 1.16, p < 0.0001), compared to the young mice following hexamethonium injection, indicating significantly elevated sympathetic nerve activity. These findings confirm that elevated SNA could contribute to aging-related hypertension. Future studies will identify glial cell-type specific mechanisms in the brainstem that contributes to age-related sympathoexcitation and increased risk for cardiovascular diseases. NHLBI-NIGMS R01HL163775 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Following acute infection, herpes simplex virus type 1 (HSV-1) establishes life-long latency in neurons. Although sensory neurons in trigeminal ganglia (TG) are primary sites for latency, the brainstem is also an important site for latency. The rationale for examining the principal sensory nucleus of the spinal trigeminal tract (Pr5) receives afferent inputs from TG. Notably, the (LC) is indirectly linked to Pr5. Our previous studies revealed that senescent cells and inflammation were detected in the Pr5 and LC of aged mice and young mice that are latently infected with HSV-1. To expand our understanding of how HSV-1 influences senescence and inflammation in Pr5 and LC, NanoString studies in mice latently infected with wild-type HSV-1 or a latency-associated transcript (LAT) null mutant (dLAT2903) was compared to age-matched uninfected C57Bl/6 male and female mice. LAT is the only viral gene abundantly expressed during latency, suggesting it influences cellular gene expression during latency. Cellular genes that regulate neuron differentiation, axonal projection, and pro-inflammatory mediators were more prevalent in mice latently infected with wild-type (wt) HSV-1 and dLAT2903 versus uninfected mice. Finally, these studies revealed that latency in Pr5 and LC is a dynamic process.