Uncovering transcriptional reprogramming during callus development in soybean: insights and implications.

Callus, a valuable tool in plant genetic engineering, originates from dedifferentiated cells. While transcriptional reprogramming during callus formation has been extensively studied in Arabidopsis thaliana, our knowledge of this process in other species, such as Glycine max, remains limited. To bridge this gap, our study focused on conducting a time-series transcriptome analysis of soybean callus cultured for various durations (0, 1, 7, 14, 28, and 42 days) on a callus induction medium following wounding with the attempt of identifying genes that play key roles during callus formation. As the result, we detected a total of 27,639 alterations in gene expression during callus formation, which could be categorized into eight distinct clusters. Gene ontology analysis revealed that genes associated with hormones, cell wall modification, and cell cycle underwent transcriptional reprogramming throughout callus formation. Furthermore, by scrutinizing the expression patterns of genes related to hormones, cell cycle, cell wall, and transcription factors, we discovered that auxin, cytokinin, and brassinosteroid signaling pathways activate genes involved in both root and shoot meristem development during callus formation. In summary, our transcriptome analysis provides significant insights into the molecular mechanisms governing callus formation in soybean. The information obtained from this study contributes to a deeper understanding of this intricate process and paves the way for further investigation in the field.

Altered resting state brain metabolic connectivity in dementia with Lewy bodies.

Although dementia with Lewy bodies (DLB) have Parkinsonism in common with Parkinson's disease (PD) or PD dementia (PDD), they have different neuropathologies that underlie Parkinsonism. Altered brain functional connectivity that may correspond to neuropathology has been reported in PD while never been studied in DLB. To identify the characteristic brain connectivity of Parkinsonism in DLB, we compared the resting state metabolic connectivity in striato-thalamo-cortical (STC) circuit, nigrostriatal pathway, and cerebello-thalamo-cortical motor (CTC) circuit in 27 patients with drug-naïve DLB and 27 age- and sex-matched normal controls using 18F-fluoro-2-deoxyglucose PET. We derived 118 regions of interest using the Automated Anatomical Labeling templates and the Wake Forest University Pick-Atlas. We applied the sparse inverse covariance estimation method to construct the metabolic connectivity matrix. Patients with DLB, with or without Parkinsonism, showed lower inter-regional connectivity between the areas included in the STC circuit (motor cortex-striatum, midbrain-striatum, striatum-globus pallidus, and globus pallidus-thalamus) than the controls. DLB patients with Parkinsonism showed less reduced inter-regional connectivity between the midbrain and the striatum than those without Parkinsonism, and higher inter-regional connectivity between the areas included in the CTC circuit (motor cortex-pons, pons-cerebellum, and cerebellum-thalamus) than those without Parkinsonism and the controls. The resting state metabolic connectivity in the STC circuit may be reduced in DLB. In DLB with Parkinsonism, the CTC circuit and the nigrostriatal pathway may be activated to mitigate Parkinsonism. This difference in the brain connectivity may be a candidate biomarker for differentiating DLB from PD or PDD.

Understanding anion-redox reactions in cathode materials of lithium-ion batteries throughin situcharacterization techniques: a review.

As the demand for rechargeable lithium-ion batteries (LIBs) with higher energy density increases, the interest in lithium-rich oxide (LRO) with extraordinarily high capacities is surging. The capacity of LRO cathodes exceeds that of conventional layered oxides. This has been attributed to the redox contribution from both cations and anions, either sequentially or simultaneously. However, LROs with notable anion redox suffer from capacity loss and voltage decay during cycling. Therefore, a fundamental understanding of their electrochemical behaviors and related structural evolution is a prerequisite for the successful development of high-capacity LRO cathodes with anion redox activity. However, there is still controversy over their electrochemical behavior and principles of operation. In addition, complicated redox mechanisms and the lack of sufficient analytical tools render the basic study difficult. In this review, we aim to introduce theoretical insights into the anion redox mechanism andin situanalytical instruments that can be used to prove the mechanism and behavior of cathodes with anion redox activity. We summarized the anion redox phenomenon, suggested mechanisms, and discussed the history of development for anion redox in cathode materials of LIBs. Finally, we review the recent progress in identification of reaction mechanisms in LROs and validation of engineering strategies to improve cathode performance based on anion redox through various analytical tools, particularly,in situcharacterization techniques. Because unexpected phenomena may occur during cycling, it is crucial to study the kinetic properties of materialsin situunder operating conditions, especially for this newly investigated anion redox phenomenon. This review provides a comprehensive perspective on the future direction of studies on materials with anion redox activity.

Reliability and Validity of Alzheimer's Disease Screening With a Semi-automated Smartphone Application Using Verbal Fluency.

Introduction: This study aimed to examine the reliability and validity of Alzheimer's disease (AD) screening with a self-administered categorical verbal fluency test using a semi-automated Android application (app; tCVFT). Furthermore, its diagnostic accuracy concerning AD was compared with both that of a conventional categorical verbal fluency test (cCVFT) administered by a health professional and the Mini-Mental State Examination (MMSE). Materials and Methods: Participants included 100 community-dwelling patients with early AD, whose Clinical Dementia Rating was either 0.5 or 1, and a further 100 sex-matched cognitively normal controls. The internal consistency and test-retest reliability of the tCVFT weighted sum score (tCVFT-WS) was examined using Cronbach's alpha and Pearson's correlation analyses (adjusted for age and education), respectively. The concurrent validity of the tCVFT-WS was examined by testing its correlations with the cCVFT weighted sum score (cCVFT-WS) and MMSE using Pearson's correlation tests. The diagnostic accuracies for early AD of the tCVFT-WS, cCVFT-WS, and MMSE were estimated and compared using receiver operating characteristic (ROC) analyses. Results: The tCVFT-WS exhibited strong internal consistency (Cronbach's alpha = 0.79). However, its test-retest reliability was moderate (r = 0.54) owing to the low test-retest reliability of the second-half responses. The patient group exhibited a higher tCVFT-WS than the control group (p < 0.001). Correlations between the tCVFT-WS, cCVFT-WS, and MMSE were significant. The tCVFT-WS's area under the ROC curve for AD was 0.861. At its optimal cutoff, the sensitivity and specificity for AD were 0.78 and 0.77, respectively. Conclusions: The self-administered tCVFT-WS, using an Android app, proved valid and reliable at distinguishing people with early AD from cognitively normal controls.

Scalable Binder-Free Freestanding Electrodes Based on a Cellulose Acetate-Assisted Carbon Nanotube Fibrous Network for Practical Flexible Li-Ion Batteries.

Herein, a freestanding cellulose acetate-carbon nanotube (CA-CNT) film electrode is presented to achieve highly flexible, high-energy lithium-ion batteries (LIBs). CA serves as a dispersing agent of CNTs and a binder-free network former. A straightforward washing can remove CA in the electrode almost completely, while the fibrous CNT network within the electrode is sustained. Furthermore, the facile fabrication enables the large-scale production of the film electrode because the CA-CNT film is processed by a conventional casting method and not by the area-limited vacuum filtration. The superior electrochemical performance and high flexibility of the full cell assembled with CA-CNT-based electrodes are maintained even at a high active material loading, which has been proven difficult to accomplish in the conventional configuration LIBs. In addition, by simply stacking six sheets of the freestanding film electrode, a capacity as high as 5.4 mA h cm-2 is achieved. The assembled pouch battery operates stably under extreme deformation. We demonstrate that the rational design of the electrode could extend the flexibility to a higher energy than that achieved with the conventional configuration. We believe that the low production cost, high flexibility, and superior electrochemical performance of the proposed freestanding film electrode can expedite the implementation of wearable gears in daily life.

Sex differences in subjective age-associated changes in sleep: a prospective elderly cohort study.

Subjective age-associated changes in sleep (AACS) and sex differences in AACS have never been prospectively investigated in elderly populations. We compared the AACS every 2 years over a total of 6 years between 4,686 community-dwelling healthy men and women aged 60 years or older who participated in the Korean Longitudinal Study on Cognitive Aging and Dementia. Sleep parameters including sleep duration, latency, and efficiency, mid-sleep time, daytime dysfunction, and overall subjective sleep quality were measured using the Pittsburgh Sleep Quality Index at baseline and at each follow-up. The effects of time and sex on subjective sleep parameters were analyzed using linear mixed-effects models. During the 6 years of follow-up, we observed that overall, sleep latency increased, while daytime dysfunction and sleep quality worsened. Significant sex differences in AACS was found, with women showing shortened sleep duration, delayed mid-sleep time, and decreased sleep efficiency over 6 years. Sleep quality worsened in both groups but a more pronounced change was observed in women. Clinicians should be cautious in determining when to treat declared sleep disturbances in this population.

Driving-Related Adverse Events in the Elderly Men: A Population-Based Prospective Cohort Study.

OBJECTIVE: This study estimated the incidence of driving-related adverse events and examined the association of cognitive function with the risk of future driving-related adverse events in the elderly Korean male population. METHODS: We analyzed 1,172 male drivers aged 60 years or older in the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD). Using the data from Korean National Police Agency, we classified the participants into three groups: safe driving (drove for 2 years after baseline without a traffic accident or repeated violations), driving cessation (stopped driving), and risky driving (one or more traffic accidents or repeated violations). We estimated the incidences of driving cessation and risky driving, and examined the effect of cognitive function on their risks. RESULTS: The incidence of driving cessation and risky driving in the Korean male drivers aged 60 years or older was 19.3 and 69.9 per 1,000 person-years respectively and increased in the late 80s. Drivers with better baseline Word List Memory Test scores showed less risky driving (OR=0.94, p=0.039). CONCLUSION: Driving-related adverse events increased in late 80s, and better memory function was protective against these events.

Efficacy of Vitamins on Cognitive Function of Non-Demented People: A Systematic Review and Meta-Analysis.

Previous evidence has suggested that vitamins might be beneficial for cognition. This systematic review aimed to investigate the efficacy of B vitamins, antioxidant vitamins, and vitamin D on the cognitive function of non-demented middle-aged or older people. Randomized or quasi-randomized controlled trials of individuals aged 40 years or older were included. PubMed/MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane Library databases, and other grey literature sources were searched up to November 2019. Their methodological quality was evaluated using the Cochrane Risk of Bias tool. Twenty-three studies on B vitamins (n = 22-1053; comprising folate, B6, and B12), nine on antioxidant vitamins (n = 185-20,469), and six on vitamin D (n = 55-4122) were included. Taking B vitamins for over 3 months was beneficial for global cognition (standardized mean difference (SMD) -0.18, 95% CI -0.30 to -0.06) and episodic memory (SMD -0.09, 95% CI -0.15 to -0.04). However, antioxidant vitamins (SMD -0.02, 95% CI -0.08 to 0.03) and vitamin D (SMD -0.06, 95% CI -0.36 to 0.23) were not. Antioxidant vitamins were beneficial for global cognition in sensitivity analyses using final measurement data as mean difference estimates (SMD, -0.04, 95% CI -0.08 to -0.01). Taking B vitamins and possibly antioxidant vitamins may be beneficial for the cognitive function of non-demented people.

Association of Low Blood Pressure with White Matter Hyperintensities in Elderly Individuals with Controlled Hypertension.

BACKGROUND AND PURPOSE: Both hypertension and hypotension increase cerebral white matter hyperintensities. However, the effects of hypotension in individuals with treated hypertension are unknown. We analyzed the association of low blood pressure with the location and amount of white matter hyperintensities between elderly individuals with controlled hypertension and those without hypertension. METHODS: We enrolled 505 community-dwelling, cognitively normal elderly individuals from the participants of the Korean Longitudinal Study on Cognitive Aging and Dementia. We measured blood pressure three times in a sitting position using a mercury sphygmomanometer and defined low systolic and diastolic blood pressure as ≤110 and ≤60 mm Hg, respectively. We segmented and quantified the periventricular and deep white matter hyperintensities from 3.0 Tesla fluid-attenuated inversion recovery magnetic resonance images. RESULTS: Low systolic blood pressure was independently associated with larger volume of periventricular white matter hyperintensity (P=0.049). The interaction between low systolic blood pressure and hypertension was observed on the volume of periventricular white matter hyperintensity (P=0.005). Low systolic blood pressure was associated with the volume of periventricular white matter hyperintensity in individuals with controlled hypertension (F1,248=6.750, P=0.010), but not in those without hypertension (P=0.380). Low diastolic blood pressure was not associated with the volumes of white matter hyperintensities regardless of presence of controlled hypertension. CONCLUSIONS: Low systolic blood pressure seems to be associated with larger volume of periventricular white matter hyperintensity in the individuals with a historyof hypertension but not in those without hypertension.

Pineal gland volume is associated with prevalent and incident isolated rapid eye movement sleep behavior disorder.

We aimed to investigate the association of pineal gland volume with the risk of isolated rapid eye movement (REM) sleep behavior disorder (RBD). We enrolled 245 community-dwelling cognitively normal elderly individuals without major psychiatric or neurological disorders at the baseline evaluation, of whom 146 completed the 2-year follow-up evaluation. We assessed RBD symptoms using the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) and defined probable RBD (pRBD) as an RBDSQ score of ≥ 5. We manually segmented the pineal gland on 3T T1-weighted brain magnetic resonance imaging and estimated its volume. The smaller the baseline pineal gland volume, the more severe the RBD symptoms at baseline. The individuals with isolated pRBD showed smaller pineal gland volumes than those without isolated pRBD. The larger the baseline pineal gland volume, the lower the risks of prevalent isolated pRBD at the baseline evaluation and incident isolated pRBD at the 2-year follow-up evaluation. Pineal gland volume showed good diagnostic accuracy for prevalent isolated pRBD and predictive accuracy for incident isolated pRBD in the receiver operator characteristic analysis. Our findings suggest that pineal gland volume may be associated with the severity of RBD symptoms and the risk of isolated RBD in cognitively normal elderly individuals.

Loss of Functional Dentition is Associated with Cognitive Impairment.

BACKGROUND: Although tooth loss is known to increase the risk of cognitive impairment and dementia, few studies have investigated the association between functional teeth including rehabilitated lost teeth and cognitive functionObjective:We investigated the associations of the numbers of functional teeth and functional occlusal units with cognitive impairment and cognitive function in late life. METHODS: The current study was conducted as a part of the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD), a community-based elderly cohort study. We analyzed 411 participants who have agreed with the additional dental exam. Geriatric psychiatrists and neuropsychologists administered the Consortium to Establish a Registry for Alzheimer's disease Assessment Packet Clinical and Neuropsychological Assessment Battery to all participants, and dentists examined their dental status. RESULTS: Higher number of functional teeth (OR = 0.955, 95% CI = 0.914-0.997, p = 0.037) and higher number of functional occlusal units (OR = 0.900, 95% CI = 0.813-0.996, p = 0.042) were associated with lower odds of cognitive impairment. When we analyzed these relationships separated by the location of teeth, only the numbers of functional teeth (OR = 0.566, 95% CI = 0.373-0.857, p = 0.007) and functional occlusal units (OR = 0.399, 95% CI = 0.213-0.748, p = 0.004) in the premolar area were associated with lower odds of cognitive impairment. CONCLUSION: Loss of functional teeth and functional occlusal units (especially in the premolar region) were associated with increased cognitive impairment.

Serum apolipoprotein A-1 concentrations and the prevalence of cardiovascular autonomic neuropathy in individuals with type 2 diabetes.

OBJECTIVE: To evaluate the relationship between levels of serum apolipoproteins and the prevalence of cardiovascular autonomic neuropathy (CAN) in type 2 diabetes. METHODS: In total, 3199 individuals with type 2 diabetes were investigated in a cross-sectional study. The diagnosis of CAN was made based on the results of a cardiovascular reflex test. Serum apolipoprotein A-I (apoA-I) and apolipoprotein B (apoB) levels were measured. RESULTS: Serum apoA-1 levels were significantly low in individuals with CAN, but there was no significant association between serum apoB levels and CAN. According to the degree of cardiovascular autonomic dysfunction, the average apoA-I levels were significantly different after adjusting for other covariates (normal, 1.32 g/l, 95% confidence interval [CI] 1.30-1.35; early, 1.29 g/l, 95% CI 1.27-1.31; definite, 1.27 g/l, 95% CI 1.25-1.30; P for trend = 0.010). In the multivariable analysis, the statistically significant association between apoA-I and CAN remained after adjusting for the risk factors (odds ratio per standard deviation increase in the log-transformed value, 0.65; 95% CI, 0.43-0.97, P = 0.036). Additional adjustments for serum high-sensitivity C-reactive protein (or fibrinogen) concentrations eliminated this relationship. CONCLUSIONS: Serum apoA-I levels are inversely associated with the prevalence of CAN in individuals with type 2 diabetes. Our data also suggest that a putatively increased risk of CAN associated with decreased apoA-I levels might be mediated by correlated increases in the levels of inflammatory markers.

Electrolyte Imbalance in Patients with Sheehan's Syndrome.

BACKGROUND: We investigated the prevalence of electrolyte imbalance and the relationship between serum electrolyte and anterior pituitary hormone levels in patients with Sheehan's syndrome. METHODS: In a retrospective study, we investigated 78 patients with Sheehan's syndrome. We also included 95 normal control subjects who underwent a combined anterior pituitary hormone stimulation test and showed normal hormonal responses. RESULTS: In patients with Sheehan's syndrome, the serum levels of sodium, potassium, ionized calcium, magnesium, and inorganic phosphate were significantly lower than those in control subjects. The prevalence of hyponatremia, hypokalemia, hypocalcemia, hypomagnesemia, and hypophosphatemia in patients with Sheehan's syndrome was 59.0% (n=46), 26.9% (n=21), 35.9% (n=28), 47.4% (n=37), and 23.1% (n=18), respectively. Levels of sodium and ionized calcium in serum were positively correlated with levels of all anterior pituitary hormones (all P<0.05). Levels of potassium in serum were positively correlated with adrenocorticotrophic hormone (ACTH) and growth hormone (GH) levels (all P<0.05). Levels of inorganic phosphate in serum were positively correlated with levels of thyroid-stimulating hormone, prolactin, and GH (all P<0.05), and levels of magnesium in serum were positively correlated with delta ACTH (P<0.01). CONCLUSION: Electrolyte imbalance was common in patients with Sheehan's syndrome. Furthermore, the degree of anterior pituitary hormone deficiency relates to the degree of electrolyte disturbance in patients with this disease.

Intensive systemic chemotherapy is effective against recurrent malignant Brenner tumor of the ovary: An analysis of 10 cases within a single center.

OBJECTIVE: Malignant Brenner tumors (MBTs) of the ovary are very rare, and their definition, biology, and treatment modality have not been established. This study investigated the clinical characteristics of MBTs and the importance of chemotherapy for recurrent disease. MATERIALS AND METHODS: We conducted a retrospective analysis of 10 patients with MBT of the ovary treated at a single tertiary center from 1991 to 2013. RESULTS: The median age was 55.5 years (range, 37-68 years). Nine of the 10 patients were symptomatic. The median size of the ovarian tumors was 10.5 cm (range, 2.5-25.0 cm). The cancer antigen-125 level was elevated in three patients. Six patients had a stage I tumor, one had a stage II tumor, two had a stage III tumor, and one had a stage IV tumor. Six patients received systemic adjuvant chemotherapy after surgery. The mean follow-up duration was 54.5 months (range, 8-173 months). Disease recurrence occurred in four of the 10 patients. The median time to recurrence was 11 months (range, 9-18 months). Two patients with locoregional recurrence showed favorable results after chemotherapy, regardless of the initial stage of the tumor. The patient with the stage IIIC tumor is alive at 13 months after recurrence on current chemotherapy. The patient with the stage IV tumor showed no evidence of the disease > 12 years after the last chemotherapy. Lastly, two patients with distant recurrence died after showing a long-term survival of 49 months and 88 months, respectively, after recurrence and intensive chemotherapy. CONCLUSION: Our results showed that systemic chemotherapy is beneficial in patients with recurrence of a primary MBT of the ovary, especially in the locoregional recurrence.

Photoaging-associated changes in epidermal proliferative cell fractions in vivo.

The epidermis is a dynamic epithelium with constant renewal throughout life. Epidermal homeostasis depends on two types of proliferative cells, keratinocyte stem cells (KSCs), and transit amplifying (TA) cells. In the case of chronologic aging, levels of KSCs tend to decrease and change functionally. However, little is known about the effect of photoaging on epidermal proliferative subtype populations. The aim of this study was to validate involucrin/beta1-integrin ratio as a molecular marker of epidermal photoaging, and to investigate the effects of photoaging caused by chronic UV exposure on the proliferative subtype populations. A total of 15 male volunteers (age range 20-24 and 77-85 years, Fitzpatrick skin phototype III-IV) provided sun-exposed and sun-protected skin samples for real-time RT-PCR, Western blot analysis and immunostaining. Fractional changes in proliferative subtype populations in photoaged and chronologically aged skins were analyzed by flow cytometry. The expression of beta1-integrin was found to be significantly reduced in photoaged skin and ratios of the expressions of involucrin to beta1-integrin were increased 2.6-fold only in elderly subjects. Interestingly, immunostaining of the sun-exposed skins of elderly subjects showed aberrant beta1-integrin expression over the basal layer and greater numbers of Ki-67-positive cells than in sun-protected buttock skin. Flow cytometric analysis revealed that the proportion of KSCs to TA cells was reversed in sun-exposed and sun-protected skins of elderly subjects. Our results suggest that KSC numbers may be lower in photoaged skin than in chronologically aged skin and could be applied to hyperplastic pattern of photoaging. These findings suggest that the epidermis of photoaged skin is impaired in terms of its proliferative potential by attempting to repair chronic UV exposure and that photoaging may be associated with alteration in the two proliferative cell fractions.

Promotive effect of minoxidil combined with all-trans retinoic acid (tretinoin) on human hair growth in vitro.

Minoxidil induces hair growth in male pattern baldness and prolongs the anagen phase. All-trans retinoic acid (ATRA) has been reported to act synergistically with minoxidil in vivo: they can enhance more dense hair regrowth than either compound alone. We evaluated the effect of minoxidil combined with ATRA on hair growth in vitro. The effect of co-treatment of minoxidil and ATRA on hair growth was studied in hair follicle organ culture. In cultured human dermal papilla cells (DPCs) and normal human epidermal keratinocytes, the expressions of Erk, Akt, Bcl-2, Bax, P53 and P21 were evaluated by immunoblot analysis. Minoxidil plus ATRA additively promoted hair growth in vitro, compared with minoxidil alone. In addition, minoxidil plus ATRA elevated phosphorylated Erk, phosphorylated Akt and the ratio of Bcl-2/Bax, but decreased the expressions of P53 and P21 more effectively than by minoxidil alone. Our results suggest that minoxidil plus ATRA would additively enhance hair growth by mediating dual functions: 1) the prolongation of cell survival by activating the Erk and Akt signaling pathways, and 2) the prevention of apoptosis of DPCs and epithelial cells by increasing the ratio of Bcl-2/Bax and downregulating the expressions of P53 and P21.

Role of staphylococcal superantigen in atopic dermatitis: influence on keratinocytes.

Staphylococcus aureus may perform an crucial function in atopic dermatitis (AD), via the secretion of superantigens, including staphylococcal enterotoxins (SE) A or B, and toxic shock syndrome toxin-1 (TSST-1). Dysregulated cytokine production by keratinocytes (KCs) upon exposure to staphylococcal superantigens (SsAgs) may be principally involved in the pathophysiology of AD. We hypothesized that lesional KCs from AD may react differently to SsAgs compared to nonlesional skin or normal skin from nonatopics. We conducted a comparison of HLA-DR or CD1a expression in lesional skin as opposed to that in nonlesional or normal skin by immunohistochemistry (IHC). We also compared, using ELISA, the levels of IL-1alpha, IL-1beta, and TNF-alpha secreted by cultured KCs from lesional, nonlesional, and normal skin, after the addition of SEA, SEB and TSST-1. IHC revealed that both HLA-DR and CD1a expression increased significantly in the epidermis of lesional skin versus nonlesional or normal skin in quite a similar manner. IL-1alpha, IL-1beta, and TNF-alpha secretion was also significantly elevated in the cultured KCs from lesional skin after the addition of SsAgs. Our results indicated that KCs from lesional skin appear to react differently to SsAgs and increased proinflammatory cytokine production in response to SsAgs may contribute to the pathogenesis of AD.

Selective COX-2 inhibitor, NS-398, inhibits the replicative senescence of cultured dermal fibroblasts.

Cyclooxygenase 2 (COX-2) is known to be increased in aged cells. Recent studies suggest that the increased expression of COX-2 may be involved in the pathogenesis of age-associated diseases such as rheumatoid arthritis and cancer. We investigated the role of COX-2 in cell cycle arrest and collagen deficiency during the aging process. Using the replicative senescence model of dermal fibroblasts, we demonstrated the increased expression of COX-2 and increased PGE(2) levels associated with replicative senescence. Replicative senescent cells showed a decreased ability to induce cell proliferation, probably due to the increased expression of the p53 protein and the decreased expression of the PCNA protein, and also showed increased expression of MMP-1, and decreased expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and procollagen. The selective COX-2 inhibitor, NS-398, can inhibit the senescence-associated increases of COX-2, PGE(2), p53 and MMP-1 expression, and the senescence-associated decreases of PCNA, TIMP-1 and procollagen expression. These results suggest that the increased level of COX-2 and higher level of PGE(2) in aged cells may play an important role in cellular senescence, and that selective COX-2 inhibitors may be useful for the intervention of skin aging.