Cortical Aquaporin-4 in relation to brain oedema and neurological function of cortical cryo-injured mice

To estimate the spatial and temporal expression of Aquaporin-4 (AQP-4) in a murine model of automated cerebral cryoinjury and correlate AQP-4 expression with development of brain oedema and neurological function. AQP-4 levels were determined quantitatively by Western blots at site of injury and at sites adjacent to and distant from injury in brains of cryoinjured (experimental) (n = 18), sham injured (n = 18) & normal mice at 24, 48, 72 h post injury. AQP-4 expression was correlated with percentage water content of brain, Neurological Severity Score (NSS) and rotarod scores. We found a 1.4-fold increase in expression of AQP-4 at the site of injury and at sites distant from injury at 24 h when compared to normal mice (p = 0.05). The increase in expression of AQP-4 24 h post injury was significantly higher in experimental group at the site of injury and at the site adjacent to the injury in the ipsilateral hemisphere when compared to the sham injured mice (p = 0.05). At 24 h post injury the median NSS score in the experimental group was 9 (interquartile range 7.25–10) and that in the sham group was 0.5 (interquartile range 0.0–1.0) (p < 0.001).At 48 and 72 h, AQP-4 expression remained elevated in the experimental group when compared to normal brain, but the levels were not significantly different from that in sham group. AQP-4 expression was significantly elevated in the ipsilateral hemisphere in the first 24 h following cerebral cortical injury in mice and this could be correlated with worsening of neurological function. Over the next 48 h, there was a trend towards decrease in AQP-4 expression that was associated with partial recovery of neurological function.     

Overexpression of tissue microRNA10b may help predict glioma prognosis

We investigated the relationship between microRNA-10b (miR-10b) expression and prognosis in human glioma patients. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to characterize the expression patterns of miR-10b in 128 glioma and 20 normal brain tissues. Clinical information – age, sex, Karnofsky Performance Status (KPS) and World Health Organization (WHO) grade – were also collected. The associations between miR-10b expression and the clinicopathological factors and outcome of glioma patients were statistically analyzed. Expression levels of miR-10b in glioma tissue were significantly higher than in normal brain tissue (P < 0.001). High-grade glioma (WHO grade III and IV) had much higher miR-10b expression levels than low-grade tumors (WHO grade I and II). Additionally, the increased miR-10b expression in the glioma tissues was significantly associated with a low KPS (P = 0.03). Kaplan–Meier survival curves and Cox regression analyses showed that overexpression of miR-10b (P = 0.01) and high grade (P = 0.02) were independent factors predicting poor outcome for glioma patients. Furthermore, subgroup analyses showed that the miR-10b expression level was significantly associated with poor overall survival in glioma patients with high grades (P < 0.001). Up-regulation of miR-10b may have value in predicting clinical outcome in glioma patients, particularly for those with high pathological grades.     

Upregulation of α-synuclein during localized radiation therapy signals the association of cancer-related fatigue with the activation of inflammatory and neuroprotective pathways

PurposeNeuroinflammatory mechanisms are associated with fatigue in neurodegenerative conditions such as Parkinson’s. The symptoms in Parkinson’s including fatigue are thought to be related to α-synuclein overexpression. This study investigated genomic correlates of fatigue experienced by men with prostate cancer receiving external beam radiation therapy (EBRT).Patients and methodsSixteen men with non-metastatic prostate cancer who were scheduled to receive EBRT were enrolled. Fatigue scores and blood were obtained at baseline (prior to EBRT, D0); one hour following initiation of EBRT (D1), day 7 (D7), day 14 (D14), midpoint (days 19–21, D21), completion (days 38–42, D42), and four weeks post-EBRT (days 68–72, D72). Gene expression profiling using microarray analysis was performed from peripheral blood and confirmatory qPCR and protein (ELISA) analyses verified the microarray results. Correlations between fatigue and gene/protein expressions were determined using a mixed model approach.ResultsMicroarray data showed significant, differential expression of 463 probesets following EBRT. SNCA had a 2.95-fold change at D21from baseline. SNCA expression was confirmed by qPCR (p < 0.001) and ELISA (p < 0.001) over time during EBRT. Fatigue scores were significantly correlated with SNCA gene expression on D14 (r = 0.55, p < 0.05) and plasma α-synuclein concentrations on D42 of EBRT (r = 0.54, p = 0.04).ConclusionFatigue experienced during EBRT may be mediated by α-synuclein overexpression. Alpha-synuclein may serve as a useful biomarker to understand the mechanisms and pathways related to the development of fatigue in this population.     

Flow diversion within seven days after stroke onset is associated with favorable outcome in anterior circulation stroke

Anterior cerebral artery (ACA) flow diversion (FD), defined as ipsilateral mean velocity (MV) of at least 30% greater than the contralateral artery, could be seen an indirect sign of leptomeningeal collateralization in the setting of middle cerebral artery occlusion. The purpose of the study was to evaluate the association between dynamic FD and functional outcome in acute anterior stroke patients with large artery occlusion. Acute middle cerebral artery (MCA) or internal carotid artery (ICA) occlusive stroke patients within 12 h were recruited. Transcranial Doppler ultrasound was done at baseline, 24 h and 7 d after onset and velocities of MCA and ACA were recorded. FD ratio was calculated by dividing the ipsilateral ACA MV by the contralateral ACA MV. FD was determined positive when FD ratio ≥1.3. Outcome was assessed by 90-day modified Rankin’s Scale (mRS). The association between FD at different time points and functional outcome were analyzed. 16 patients (median age of 67 and 75% were male) were recruited. FD ratio showed a trend of decline but did not reach statistical significance (p = 0.056). The proportion of FD at baseline (p = 0.026), 24 h (p = 0.001) and 7d (p = 0.044) was significantly higher in patients with favorable outcome. Higher FD ratio at baseline (p = 0.02) and 24 h (p = 0.003) were significantly associated with favorable outcome. These results suggested that FD ratio showed a trend of decline after stroke onset. Presence of FD within 7 days was associated with favorable functional outcome in acute MCA/ICA occlusive stroke patients.     

A comparison of the oxygen cost and physiological responses to running in children with and without Developmental Coordination Disorder

The aim of this study was to compare the oxygen cost of running in boys with and without Developmental Coordination Disorder (DCD). Fourteen boys with DCD (9.1 ± 1.4 yr) and 16 typically developing (TD) controls (9.4 ± 1.3 yr) were tested on two separate occasions at least a week apart. On the first visit, motor proficiency, body composition and maximal aerobic capacity were established. On the second visit, oxygen consumption was determined via indirect calorimetry while participants ran at three submaximal speeds (7.2 km/h, 8.0 km/h and 8.8 km/h) on a motorised treadmill for 4 min each. Additional physiological responses such as blood lactate, respiratory exchange ratio (RER), heart rate, salivary alpha amylase and pain threshold were monitored at baseline and after each submaximal effort. Although there were no differences in the oxygen cost of running at all three speeds, the boys with DCD had higher blood lactate concentration (7.2 km/h, p = 0.05; 8.0 km/h p = 0.019), heart rate (p ≤ 0.001), RER (8.0 km/h, p = 0.019; 8.8 km/h, p = 0.001), salivary alpha amylase (8.0 km/h, p = 0.023; 8.8 km/h, p = 0.020) and a lower pain threshold (p < 0.01). The higher overall metabolic cost of running in boys with DCD as indicated by the higher RER, heart rate and blood lactate concentrations, together with the higher levels of sympathoadrenal medullary activity and sensitivity to pain, may be deterring factors for participation in physical activity in this population.     

Increased serum S100B concentration correlates with hippocampal S100B overexpression and cellular damage following chronic cerebral hypoperfusion

To develop a sensitive and convenient clinical index of brain injury, we investigated the relationship between serum S100B concentration and the expression of S100B in the hippocampus at multiple time points following permanent ligation of the bilateral common carotid artery (2vo). Ninety Sprague–Dawley rats were divided into a control group (n = 6), model group (n = 42), and sham operation (SO) group (n = 42). The model group was subjected to permanent 2vo ligation, while the bilateral common carotid artery was isolated but not ligated in SO group rats. A control group received no treatment. The SO and model groups were divided into 7 subgroups of six rats each examined at 6, 12, 24, 48, or 72 h, as well as 7 and 14 d after treatment. Dynamic changes in serum S100B concentration was measured by ELISA, the S100B mRNA expression in hippocampus by RT-PCR, and hippocampal CA1 S100B protein expression by immunohistochemistry. The degeneration of neurons during chronic cerebral hypoperfusion was well correlated with the elevation of serum S100B, as well as with hippocampal S100B mRNA expression and S100B protein overexpression in the hippocampal CA1. Thus, serum S100B concentration during chronic cerebral hypoperfusion reflects the extent and progression of brain injury.     

Fasting induced kisspeptin signaling suppression is regulated by glutamate mediated cues in adult male rhesus macaque (Macaca mulatta)

Kisspeptin signaling is suppressed by short term fasting. It has been reported that hypothalamic Kiss1 and Kiss1r mRNA expression decreased after 48 h of fasting in male rhesus monkey. But the mechanism involved in the reduction of kisspeptin signaling after 48 h of fasting is unknown. Recent studies have suggested the role of afferent excitatory and inhibitory pathways in the regulation of kisspeptin neurons. Therefore, this study was designed to observe the changes in the glutamate and GABA signaling during fed and 48 h fasting states by performing immunofluorescence to examine the interaction of kisspeptin neurons with NR1 subunit of NMDA receptors and by performing SYBR green qRT-PCR to measure and quantify the levels of Kiss1, Kiss1r, NR1 and GAD67 mRNA in the POA and MBH of adult male rhesus macaque (Macaca mulatta) during 48 h of fasting (n = 2) and fed ad libitum (n = 2). Plasma testosterone (p < 0.05) and blood glucose levels were significantly (p < 0.001) decreased after short term fasting. Our results clearly showed that expression of hypothalamic Kiss1, Kiss1r and NR1 mRNA was significantly (p < 0.05) reduced in adult male rhesus monkeys which were fasted for 48 h as compared to those which were fed ad libitum. There was no clear difference in the GAD67 mRNA contents between the two groups. Number of kisspeptin neurons and the interactions of kisspeptin neurons with NR1 were significantly (p < 0.05) reduced after 48 h fasting. These observations suggest that decreased kisspeptin signaling during fasting may occur due to reduction in glutamatergic inputs to kisspeptin neurons. Our results also suggest that fasting induced suppression of kisspeptin signaling is not mediated through GABAergic neurons.     

Reduced gray matter volume in psychotic disorder patients with a history of childhood sexual abuse

Childhood trauma is associated with smaller gray matter volume, similar to the pattern seen in psychotic disorders. We explored the relationship between childhood abuse, psychosis, and brain volume in a group of 60 individuals with a psychotic disorder and 26 healthy control subjects. We used voxel-based morphometry (VBM) to quantify gray and white matter volume and the Childhood Trauma Questionnaire (CTQ) to measure childhood abuse. Within the psychotic disorder group, total gray matter volume was inversely correlated with the severity of childhood sexual abuse (r = ? .34, p = .008), but not the other types of abuse. When the 24 patients with sexual abuse were compared with demographically matched samples of 23 patients without sexual abuse and 26 control subjects, only patients with a history of sexual abuse had reduced total gray matter volume (t(48) = 2.3, p = .03; Cohen's d = .63). Voxel-based analysis revealed a cluster in the prefrontal cortex where volume was negatively correlated with sexual abuse severity. Voxel based comparison of the three matched groups revealed a similar pattern of results, with widespread reductions in psychosis patients with sexual abuse relative to controls that were not found in psychosis patients without sexual abuse. These findings indicate that some of the variance of gray matter volume in psychotic disorders can be explained by a history of sexual abuse.     

Prognosis of status epilepticus (SE): Relationship between SE duration and subsequent development of epilepsy

In animal models, SE duration is related to epileptogenesis. Data in humans are scarce, mainly in NCSE; therefore, we aimed to study the prognosis of SE de novo and which factors may influence subsequent development of epilepsy.MethodsWe evaluated patients with SE without previous epilepsy at our hospital (February 2011–February 2014), including demographics, etiology, number of AEDs, duration of SE, mortality, and occurrence of seizures during follow-up.ResultsEighty-nine patients were evaluated. Median age was 69 (19–95) years old. Among them, 33.7% were convulsive. Regarding etiology, 59 were considered acute symptomatic (41 lesions, 18 toxic–metabolic), 17 remote or progressive symptomatic, and 13 cryptogenic. The median recovery time was 24 h (30 min–360 h). In-hospital mortality was 29% (n = 26). After a median follow-up of 10 months, 58.7% of survivors (n = 37) showed seizures. Subsequently, we analyzed which factors might be related to the development of epilepsy, and we found that epilepsy development was more frequent with longer SE duration (37 vs. 23 h, p = 0.004); furthermore, patients with a toxic–metabolic etiology developed epilepsy less frequently (33% vs. 67%; p = 0.022). Epilepsy was also correlated (tendency) with focal SE (p = 0.073), a lesion in neuroimaging (p = 0.091), and the use of 2 or more AEDs (p = 0.098). Regarding SE duration, a cutoff of above 24 h was clearly related to chronic seizures (p = 0.014); however, combining etiology and duration, the association of longer SE and epilepsy was significant in acute lesional SE (p = 0.034), but not in epilepsy with cryptogenic or remote/progressive etiology. After a logistic regression, only a duration longer than 24 h (OR = 3.800 (1.277–11.312), p = 0.016) was found to be an independent predictor of the development of epilepsy.ConclusionIn patients with SE, the longer duration is associated with an increased risk of subsequent epilepsy at follow-up, mainly in symptomatic SE due to an acute lesion. It is unclear if it might be the result of a more severe injury causing both prolonged seizures and subsequent epilepsy, and therefore whether more aggressive treatment in this group might avoid this possibility. Most of the patients with cryptogenic or remote/progressive SE developed epilepsy regardless of SE duration.This article is part of a Special Issue entitled “Status Epilepticus”.     

Hypoxia and nicotine effects on Pituitary adenylate cyclase activating polypeptide (PACAP) and its receptor 1 (PAC1) in the developing piglet brainstem

Pituitary adenylate cyclase activating polypeptide (PACAP) and its cognate receptor 1 (PAC1), have been implicated in the pathophysiology of the Sudden Infant Death Syndrome (SIDS). Two main risk factors for SIDS are prone sleeping and cigarette smoke exposure. Using piglet models of these risk factors, intermittent hypercapnic hypoxia (IHH-mimicking rebreathing in prone position) and nicotine (main reinforcing element of cigarettes), this study aimed to determine their effects on PACAP and PAC1 protein expression in the medulla. IHH was delivered for 1 (n = 7), 2 (n = 6), 3 (n = 6) and 4 (n = 7) days prior to euthanasia at 13–14 days of age, while nicotine (n = 7) was continuous for the first 14 days of life. An additional group of combined nicotine and 1 day IHH (1DIHH) was studied to determine the combined effects of the risk factors. Changes in expression were seen after the acute 1DIHH exposure (none after repeated daily exposures) and included a decrease in PACAP in the dorsal motor nucleus of vagus (DMNV; p = 0.024), nucleus of the solitary tract (NTS; p = 0.024) and the gracile nucleus (GRAC; p = 0.001), and a decrease in PAC1 in the NTS (p = 0.01). No PACAP change was noted in the nicotine-exposed piglets, however, a decrease in PAC1 was found in the DMNV (p = 0.02). IHH exposure in piglets with pre-exposure to nicotine led to a significant decrease in PACAP in the Grac (p = 0.04) but had no effect on PAC1. These findings show for the first time, the vulnerability of PACAP in the brainstem during early development to an acute hypercapnic hypoxic exposure and that those effects are greater than from nicotine exposure.     

Increasing escitalopram dose is associated with fewer discontinuations than switch or combination approaches in patients initially on escitalopram 10 mg

PurposeTo examine the relationship between different intervention approaches and subsequent real-life outcomes in patients changing treatment from escitalopram 10 mg.MethodThis was a retrospective cohort study of patients starting antidepressant treatment between 2002 and 2004. Data were extracted from a US health-insurance reimbursement claims database. Eligible patients started escitalopram 10 mg and changed within 3 months to: escitalopram ≥ 20 mg; another antidepressant; or a combination of escitalopram with another antidepressant. Medication persistence and healthcare costs over 3 months were compared between the treatment groups.ResultsOverall, 37,791 patients started escitalopram 10 mg. Of the 12,830 patients (34%) who changed treatment, 56% increased escitalopram dose, 26% switched antidepressant and 18% combined escitalopram with another antidepressant. Patients in the switch and combination groups had significantly higher rates of non-persistence (56% and 91%, respectively) vs the dose-increase group (39%; both P < 0.001). Combination-group patients incurred significantly greater costs vs the dose-increase group ($ 2805 vs $ 1767, respectively; P < 0.001).ConclusionResults suggest that increasing escitalopram dose in patients responding inadequately to 10 mg is associated with higher persistence rates vs the other treatment approaches. Receiving an increased dose of escitalopram was associated with significantly lower costs than combining escitalopram 10 mg with another antidepressant.     

Contribution of the spinal cord BDNF to the development of neuropathic pain by activation of the NR2B-containing NMDA receptors in rats with spinal nerve ligation

The NMDA receptor and the brain-derived neurotrophic factor (BDNF) are involved in central sensitization and synaptic plasticity in the spinal cord. To determine whether the spinal cord BDNF contributes to the development and maintenance of neuropathic pain by activation of the dorsal horn NR2B-containing NMDA (NMDA-2B) receptors, this study was designed to investigate if alterations in BDNF and its TrkB receptor in the spinal dorsal horn would parallel the timeline of the development of neuropathic pain in lumbar 5 (L5) spinal nerve ligated (SNL) rats. The enzyme-linked immunosorbent assay (ELISA) showed that the BDNF concentration significantly increased during 24 h post-surgery, and the maximal enhancement lasted for 48 h. It declined as time progressed and returned to the level of pre-operation at 28 days after SNL. In parallel with the alteration of BDNF concentration in the spinal dorsal horn, the 50% paw withdrawal threshold (PWT) of the ipsilateral hind paw in SNL rats also showed a significant decrease during 24–48 h after SNL as compared with those in sham-operated rats. The correlation analysis revealed that the BDNF concentration had a negative correlation with 50% PWT in early stage (0–48 h) (r = -0.974, p = 0.001), but not late stage (3–28 days) (r = 0.3395, p = 0.6605), after SNL. Similarly, the immunohistochemical staining revealed that a significant up-regulation of BDNF expression in the spinal dorsal horn appeared as early as 12 h post-operation in SNL rats, peaked at 24–48 h, declined at 3 days and disappeared at 14 days after SNL. In contrast, an increase in NMDA-2B receptors expression in the spinal dorsal horn was delayed to 48 h after SNL. The increase reached peak at 3 days, lasted for 14 days, and returned to the control level of pre-operation at 28 days after SNL. The maximal enhancement of BDNF expression occurred in early stage (24–48 h) after nerve injury, while the peak of NMDA-2B receptors expression appeared in late stage (3–14 days) post-nerve ligation. As compared with the dynamic changes of 50% PWT in the timeline after nerve injury, the maximal enhancement of BDNF expression closely paralleled the maximal decline in the slope of 50% PWT, while the peak of NMDA-2B receptors expression corresponded with the plateau of the decreased 50% PWT. Therefore, the increased BDNF in the spinal dorsal horn was likely to be associated with the initiation of neuropathic pain in early stage (0–48 h), while the activation of NMDA-2B receptors was involved in the maintenance of persistent pain states in late stage (2–14 days) after nerve injury. Moreover, the present study also demonstrated that the BDNF/TrkB-mediated signaling pathway within the spinal cord might be involved in the induction of neuropathic pain in early stage after nerve injury, and the selective NMDA-2B receptors antagonist (Ro 25-6981) almost completely blocked the BDNF-induced mechanical allodynia in all of the tested rats. These data suggested that the BDNF/TrkB-mediated signaling pathway in the spinal cord was involved in the development of nerve injury-induced neuropathic pain through the activation of dorsal horn NMDA-2B receptors.     

KPNA2 predicts long term survival in patients with anaplastic oligoastrocytomas

The family of karyopherins comprises importins and exportins which are both involved in nucleocytoplasmic shuttling. Increased levels of karyopherin a2/importin 1 (KPNA2) and chromosome region maintenance protein 1/exportin 1 (CRM1) have been associated with poorer prognosis in patients with infiltrative astrocytomas. Isocitrate dehydrogenase 1 gene (IDH1) R132H mutation status was also recently identified as a prognostic factor for malignant gliomas. We evaluated KPNA2 and CRM1, as well as the IDH1 mutation status, as possible novel biomarkers for World Health Organization grade III anaplastic oligoastrocytomas (AOA). We analyzed nuclear expression of KPNA2 by immunohistochemistry in 72 primary anaplastic gliomas (29 AOA, 24 anaplastic astrocytomas, 19 anaplastic oligodendrogliomas). The IDH1 mutation status was also determined in patients with anaplastic astrocytomas and AOA, and AOA patients were additionally evaluated for CRM1 nuclear expression. Long term survivors (LTS; >8 years) with AOA showed lower KPNA2 expression levels compared to non-LTS (p = 0.005). KPNA2 expression (⩾5% versus <5%, 1–<5%, median) was found to correlate inversely with overall survival (OS) and progression-free survival (PFS) in our overall series as well as in the AOA group (anaplastic gliomas: OS p = 0.017; PFS p = 0.033; AOA: OS p = 0.017, PFS p = 0.040). Mutant IDH1-R132H was detected in 69% of the AOA cohort; a combination of KPNA2 low expression and mutant IDH1-R132H was only seen in LTS (p = 0.050). No differences between the histological subtypes were observed in terms of KPNA2 expression and IDH1-R132H mutation status. To our knowledge this is the first time it has been shown that KPNA2 expression may have potential as a prognostic biomarker for AOA as well.     

Sleep duration versus sleep insufficiency as predictors of cardiometabolic health outcomes

ObjectiveThe objective of the present study was to investigate the relationship between sleep insufficiency and sleep duration, particularly regarding negative cardiometabolic health outcomes already considered to be affected by reduced sleep time.MethodsA total of N = 30,934 participants from the 2009 Behavioural Risk Factor Surveillance System (BRFSS) answered questions about their sleep duration as well as subjective feelings of sleep insufficiency. Outcomes included body mass index (BMI), obesity (BMI ? 30 kg m^?2) and history of hypertension, diabetes, hypercholesterolaemia, heart attack and stroke. Linear and logistic regression models examined whether cardiometabolic outcomes were associated with (1) sleep duration alone, (2) sleep insufficiency alone and (3) the combined effect of sleep duration and sleep insufficiency.ResultsResults indicated that, when examined alone, sleep duration <5 h (versus 7 h) was related to BMI (B = 2.716, p < 0.01), obesity (B = 2.080, p < 0.000001), diabetes (B = 3.162, p < 0.000001), hypertension (B = 2.703, p < 0.000001), hypercholesterolaemia (B = 1.922, p < 0.00001), heart attack (B = 4.704, p < 0.000001) and stroke (B = 4.558, p < 0.000001), and sleep insufficiency (days per week, continuous) was related to BMI (B = 0.181, p < 0.01), obesity (B = 1.061, p < 0.000001) and hypercholesterolaemia (B = 1.025, p < 0.01). All of these relationships remained significant after adjustment for covariates, except for diabetes and sleep duration. Also, after adjustment, a significant relationship between insufficient sleep and hypertension emerged (B = 1.039, p < 0.001). When evaluated together, after adjustment for covariates, significant relationships remained between sleep duration <5 h (versus 7 h) and BMI (B = 1.266, p < 0.05), obesity (B = 1.389, p < 0.05), hypertension (B = 1.555, p < 0.01), heart attack (B = 2.513, p < 0.01) and stroke (B = 1.807, p < 0.05). It should be noted that relationships between sleep duration >9 h (versus 7 h) were seen for heart attack (B = 1.863, p < 0.001) and stroke (B = 1.816, p < 0.01). In these models, sleep insufficiency was associated with hypercholesterolaemia (B = 1.031, p < 0.01) and hypertension (B = 1.027, p < 0.05).ConclusionsThese analyses show that both sleep duration and insufficiency are related to cardiometabolic health outcomes, and that when evaluated together, both variables demonstrate unique effects.     

Partial sleep deprivation activates the DNA damage response (DDR) and the senescence-associated secretory phenotype (SASP) in aged adult humans

Age-related disease risk has been linked to short sleep duration and sleep disturbances; however, the specific molecular pathways linking sleep loss with diseases of aging are poorly defined. Key cellular events seen with aging, which are thought to contribute to disease, may be particularly sensitive to sleep loss. We tested whether one night of partial sleep deprivation (PSD) would increase leukocyte gene expression indicative of DNA damage responses (DDR), the senescence-associated secretory phenotype (SASP), and senescence indicator p16^INK4a in older adult humans, who are at increased risk for cellular senescence. Community-dwelling older adults aged 61–86 years (n = 29; 48% male) underwent an experimental partial sleep deprivation (PSD) protocol over 4 nights, including adaptation, an uninterrupted night of sleep, partial sleep deprivation (sleep restricted 3–7 AM), and a subsequent full night of sleep. Blood samples were obtained each morning to assess peripheral blood mononuclear cell (PBMC) gene expression using Illumina HT-12 arrays. Analyses of microarray results revealed that SASP (p < .05) and DDR (p = .08) gene expression were elevated from baseline to PSD nights. Gene expression changes were also observed from baseline to PSD in NFKB2, NBS1 and CHK2 (all p’s < .05). The senescence marker p16^INK4a (CDKN2A) was increased 1 day after PSD compared to baseline (p < .01), however confirmatory RT-PCR did not replicate this finding. One night of partial sleep deprivation activates PBMC gene expression patterns consistent with biological aging in this older adult sample. PSD enhanced the SASP and increased the accumulation of damage that initiates cell cycle arrest and promotes cellular senescence. These findings causally link sleep deprivation to the molecular processes associated with biological aging.