Biomedical subjects

J Y Wei

Publications and source records attributed to J Y Wei.

At least 37 records · Page 2Linked to original sources

PubMed2000

Effect of CCK pretreatment on the CCK sensitivity of rat polymodal gastric vagal afferent in vitro.

To prevent the blood-borne interference and reflex actions via neighboring organs and the central nervous system, the study was conducted in an in vitro isolated stomach-gastric vagus nerve preparation obtained from overnight-fasted, urethan-anesthetized rats. Afferent unit action potentials were recorded from the gastric branch of the vagus nerve. The left gastric artery was catheterized for intra-arterial injection. In vitro we found that 1) 55/70 gastric vagal afferents (GVAs) were polymodal, responding to CCK-8 and mechanical stimuli, 13 were mechanoreceptive, and 2 were CCK-responsive; 2) sequential or randomized intra-arterial injections of CCK-8 (0.1-200 pmol) dose-dependently increased firing rate and reached the peak rate at 100 pmol; 3) the action was suppressed by CCK-A (Devazepide) but not by CCK-B (L-365,260) receptor antagonist; 4) neither antagonist blocked the mechanosensitivity of GVA fibers. These results are consistent with corresponding in vivo well-documented findings. Histological data indicate that the layered structure of the stomach wall was preserved in vitro for 6-8 h. Based on these results, it seems reasonable to use the in vitro preparation for conducting a study that is usually difficult to be performed in vivo. For instance, because there was no blood supply in vitro, the composition of the interstitial fluid, i.e., the ambient nerve terminals, can be better controlled and influenced by intra-arterial injection of a defined solution. Here we report that acutely changing the ambient CCK level by a conditioning stimulus (a preceding intra-arterial injection of increasing doses of CCK-8) reduced the CCK sensitivity of GVA terminals to a subsequent test stimulus (a constant dose of CCK-8 intra-arterial injection).

Action Potentials↗

PubMed1999

Influence of age on hypoxia/reoxygenation-induced DNA fragmentation and bcl-2, bcl-xl, bax and fas in the rat heart and brain.

To test the hypothesis that the aging mammalian heart and brain might have increased vulnerability to acute stress, DNA fragmentation was studied after hypoxia-reoygenation in young adult (6 months) and old (22-24 months) F344 rats. Heart and brain tissue were examined at the following time points: 30, 60, or 90 min of hypoxia (H, 5% O2, 95% N2) plus 2 h of reoxygenation (R, room air, 21% O2). With increasing duration of hypoxia preceding the reoxygenation, the extent of DNA fragmentation (in situ terminal dUTP nick end labeling, TUNEL, positive cells) was progressively higher in both age groups, greater in the old compared to that of the young adult rat. The levels of the anti-apoptotic proteins bcl-2 and bcl-xL, were similar in young and old at baseline and tended to increase in both age groups after hypoxia/reoxygenation. The pro-apoptotic protein, bax, was higher at baseline in the old; it rose after hypoxia/reoxygenation in the young adult heart and brain, but was unchanged in the old heart and was decreased in the old brain. The ratios of bcl-2/bax and of bcl-xL/bax were higher in the old heart and brain compared to that in the young adult after hypoxia/reoxygenation. Thus, compared to that of the young adult, the heart and brain of the old rat have lower thresholds and are more vulnerable to injury induced by hypoxia/reoxygenation, despite rapid and heightened expression of the anti-apoptotic proteins bcl-2 and bcl-xl. This could be due partly to the age-associated increase in the basal expression of the pro-apoptotic protein bax, as well as possibly other factors.

Aging↗

PubMed1999

Cell-by-cell scanning of whole mitochondrial genomes in aged human heart reveals a significant fraction of myocytes with clonally expanded deletions.

Quantitative information on the cell-to-cell distribution of all possible mitochondrial DNA (mtDNA) mutations in young and aged tissues is needed to assess the relevance of these mutations to the aging process. In the present study, we used PCR amplification of full-length mitochondrial genomes from single cells to scan human cardiomyocytes for all possible large deletions in mtDNA. Analysis of more than 350 individual cells that were derived from three middle-aged and four centenarian donors demonstrates that while most of the cells contain no deletions, in certain cardiomyocytes a significant portion of the mtDNA molecules carried one particular deletion. Different affected cells contained different deletions. Although similar numbers of cells were screened for each donor, these deletion-rich cells were found only in the hearts of old donors, where they occurred at a frequency of up to one in seven cells. These initial observations demonstrate the efficiency of the method and indicate that mitochondrial mutations have the potential to play an important role in human myocardial aging.

Aged↗

PubMed1999

Intracisternal sauvagine is more potent than corticotropin-releasing factor to decrease gastric vagal efferent activity in rats.

Consecutive intracisternal (ic) injections of corticotropin-releasing factor (CRF) (21, 63, and 126 pmol, ic) or sauvagine (2.1, 6.3, and 21 pmol, ic) decreased gastric vagal efferent multiunit discharge (GVED) to 82%, 75% and 69% and 71%, 40% and 21%, respectively, from preinjection basal levels (taken as 100%). The inhibitory action was dose related (magnitude and duration of the response, 7-45 min). The CRF antagonist, [D-Phe12,Nle21,38,Calpha-MeLeu37]-rCRF12-4 1 (6.25 nmol, ic) increased GVED by 43.5+/-4.3% and blocked the decrease in GVED induced by CRF (21 pmol, ic) for >90 min with a complete recovery after 3 h. Vehicles (injected intracisternally) had no effect. These data indicate that: 1) CRF injected intracisternally decreases GVED through the activation of CRF receptors and sauvagine is more potent than CRF to inhibit GVED; and 2) endogenous CRF exerts an inhibitory tone on basal GVED in urethane-anesthetized rats undergoing surgery.

Action Potentials↗

PubMed1999

Ischemia-reperfusion in the adult mouse heart influence of age.

Age-related changes in the mouse heart after ischemia-reperfusion have not been well characterized. To test the hypothesis that advanced age was associated with increased susceptibility to myocardial injury after ischemia/reperfusion, we studied the hearts of young adult and old mice. In young adult (6-8 months) and aged (22-24 months) C57 BL/6 mice, we performed left anterior descending coronary artery ligation and subjected the hearts to 45 min of ischemia followed by varying periods of reperfusion of 15 min, 1 h, 4 h, and 24 h. We found that there was a significant age difference in the size of the infarct between the young adult and old hearts. There was also greater damage in the old hearts in terms of contraction band necrosis, myofiber tears, DNA fragmentation, and mitochondrial disruption. Thus, the old heart is more susceptible to injury after ischemia-reperfusion. This may be partly due to an age-associated decrease in coronary circulation and collateral flow, as well as other factors.

Aging↗

PubMed1999

Medication management capacity in highly functioning community-living older adults: detection of early deficits.

OBJECTIVE: The Drug Regimen Unassisted Grading Scale (DRUGS) was developed and employed in testing the hypothesis that the inability to take medication independently may correlate with the presence of cognitive impairment. DESIGN: Cross-sectional study. SETTING: Two continuing care retirement facilities in the Greater Boston area. PARTICIPANTS: The study population included outpatients > or = 70 years old. MEASUREMENTS: We developed a novel performance-based measure, the DRUGS tool, involving a step-wise progression of four tasks: (1) identification; (2) access; (3) dosage; and (4) timing. RESULTS: Fifty-nine participants aged 84.2 +/- 5.1 years (mean +/- SD) completed the study. The DRUGS tool score was inversely related to age (r = -.41, P = .001). Compared with independent-living, residence in assisted-living was associated with lower DRUGS tool scores (82.0% vs 93.8%, P = .009). The DRUGS tool score was associated with self-reported Medication Management capacity (94.8% able vs 86.2% unable to take medications independently by self-report, P = .047). Both DRUGS tool score and self-reported Medication Management capacity were associated with MMSE (P = .0008 and P = .044, respectively). The multivariate model, with DRUGS tool Summary Score as the dependent variable, adjusted for age and sex, included MMSE (P = .023) and self-reported IADL (P = .038). CONCLUSION: There is an association between performance on the DRUGS tool and level of cognitive function. The DRUGS tool represents a unique individualized, yet standardized, assessment of the ability to function independently for ambulatory older persons. It may be useful for identifying those highly functioning older persons, at an early phase of cognitive decline, in whom targeted intervention would likely be most effective and efficient.

Activities of Daily Living↗

PubMed1999

The power of ageism on physical function of older persons: reversibility of age-related gait changes.

OBJECTIVE: To test the hypothesis that age-associated changes in physical function, particularly walking performance, are influenced by ageism and that the activation of positive sterotypes of aging can partially reverse these changes. DESIGN: Randomized intervention study. SETTING: General community. PARTICIPANTS: Forty-seven community-dwelling men and women (63-82 years old) who walked independently and described themselves as healthy. INTERVENTION: Thirty-minute exposure to the subconscious reinforcement of either a positive or negative stereotype of aging while subjects played a computer game. MEASUREMENTS: Pre- and postintervention measures of gait speed and percent swing time (the time spent with one foot in the air during walking). Health and psychosocial status were also evaluated. RESULTS: Significant increases in walking speed (9%+/-2%; P < .001) and percent swing time (percent change: 1.1%+/-0.4%; P = .023) were observed in subjects who received reinforcement of positive stereotypes of aging. Gait speed and swing time did not change in those who received reinforcement of negative stereotypes of aging. The observed improvements in gait were related to the positive intervention, but were not related to age, gender, health status, or psychosocial status. CONCLUSIONS: Stereotypes of aging apparently have a powerful impact on the gait of older persons. Interventions designed to enhance perceptions of old age may prove beneficial in helping to improve gait and functional independence among older persons. In the future, positive changes in society's view of aging may also help to reduce and prevent age-related declines in function and the associated deleterious consequences.

Activities of Daily Living↗

PubMed1999

Central autonomic activation by intracisternal TRH analogue excites gastric splanchnic afferent neurons.

Intracisternal (ic) injection of thyrotropin-releasing hormone (TRH) or its stable analogue RX 77368 influences gastric function via stimulation of vagal muscarinic pathways. In rats, the increase in gastric mucosal blood flow evoked by a low ic dose of RX 77368 occurs via release of calcitonin gene-related peptide from capsaicin-sensitive afferent neurons, most probably of spinal origin. In this study, the effect of low ic doses of RX 77368 on afferent impulse activity in splanchnic single fibers was investigated. The cisterna magna of overnight-fasted, urethan-anesthetized Sprague-Dawley rats was acutely cannulated, and fine splanchnic nerve twigs containing at least one fiber responsive to mechanical probing of the stomach were isolated at a site immediately distal to the left suprarenal ganglion. Unit mechanoreceptive fields were encountered in all portions of the stomach, both superficially and in deeper layers. Splanchnic afferent unit impulse activity was recorded continuously during basal conditions and in response to consecutive ic injections of saline and RX 77368 (15-30 min later; 1.5 or 3 ng). Basal discharge rates ranged from 0 to 154 impulses/min (median = 10.2 impulses/min). A majority of splanchnic single units with ongoing activity increased their mean discharge rate by >/=20% after ic injection of RX 77368 at either 1.5 ng (6/10 units; median increase 63%) or 3 ng (19/24 units; median increase 175%). Five units lacking impulse activity in the 5-min before ic RX 77368 (3 ng) were also excited, with the onset of discharge occurring within 1.0-5.0 min postinjection. In units excited by ic RX 77368, peak discharge occurred 15.6 +/- 1.3 min after injection and was followed by a decline to stable activity levels </=20-40 min thereafter. In a few cases (4/24), ic RX 77368 (3 ng) inhibited the impulse activity of initially active units, with a time course comparable to that seen in units excited by the same treatment. The pattern of discharge in most units was not suggestive of mechanical modulation of activity by rhythmic gastric contractions. The data demonstrate that low ic doses of TRH analogue induce sustained increases in afferent discharge in a substantial proportion of splanchnic neurons innervating the rat stomach. These findings support the notion that splanchnic afferent excitation occurs concomitantly with vasodilatory peptide release from gastric splanchnic afferent nerve terminals after ic TRH-induced autonomic activation.

Animals↗

PubMed1999

Is age a negative prognostic indicator in HIV infection or AIDS?

To better understand disease progression in older persons with human immunodeficiency virus (HIV infection or acquired immunodeficiency syndrome (AIDS), we studied patients aged 50 years and older hospitalized with a diagnosis of HIV infection or AIDS between January 1985 and October 1995. Data collected included demographics, opportunistic infections, comorbid disease, neurologic dysfunction, and antiretroviral therapy. A total of 86 patients with a mean age of 54.3 years was identified. Pneumocystis carinii pneumonia was the most frequent opportunistic infection (43%). Hypertension was the most common previous medical condition (38%). Other comorbid disease was present in less than 15% of the subjects. Fifty-seven patients (66%) had neurologic impairment, with 30 requiring treatment for delirium. In these 30, 23 (77%) had anemia, infection, or both. The median length of survival following the diagnosis of AIDS was 18.5 months, for HIV it was 48 months. The median survival following the diagnosis of AIDS in patients who received antiretroviral therapy was 22 months compared with 11 months for those who did not receive antiretroviral therapy (p < 0.0004). Multivariable analysis found that antiretroviral therapy was the only independent predictor of survival after the diagnosis of AIDS. In contrast to previous studies, the present findings suggest that older age may not necessarily be associated with more rapid disease progression and reduced survival times in persons with HIV infection or AIDS. In those patients with delirium, many may have readily treatable conditions (anemia and/or infection). The absence of significant comorbid disease and the access to antiretroviral therapy may be in part responsible for the longer survival times obtained in this cohort compared to that reported previously.

Aging↗

PubMed1999

Estrogen therapy and aggressive behavior in elderly patients with moderate-to-severe dementia: results from a short-term, randomized, double-blind trial.

The authors used a randomized, double-blind, placebo-controlled clinical trial study design to investigate the efficacy and safety of short-term estrogen therapy in decreasing aggressive behaviors in elderly patients with moderate-to-severe dementia. Estrogen therapy was associated with lower total aggression scores (P<0.030) and with decreased frequency of physical aggression (P<0.019) over the 4-week trial. Verbally aggressive behaviors were decreased relative to control subjects, although this effect was not statistically significant. No drug-vs.-placebo differences were found for resistive, sexual, or self-directed aggressive behaviors. No adverse effects from the estrogen were observed during the course of the study.

Activities of Daily Living↗

PubMed1998

Mutational scanning of mitochondrial DNA by two-dimensional electrophoresis.

An expedient, accurate, and cost-efficient test was developed to scan critical regions of the mitochondrial genome for all possible mutations by two-dimensional DNA electrophoresis. The test involves a two-step multiplex PCR amplification: a long-distance PCR to amplify almost the entire mitochondrial genome, which then serves as template for the amplification of 25 short PCR fragments in two multiplex groups corresponding to regions implicated in human diseases. The mixture of fragments was subsequently subjected to two-dimensional electrophoretic separation, first by size in a nondenaturant polyacrylamide gel and then on the basis of basepair sequence in a denaturing gradient polyacrylamide gel. This latter process of denaturing gradient gel electrophoresis is a most accurate form of mutation detection on the basis of differences in melting behavior of mutant and wildtype fragments. Evaluation of the method using samples with known homoplasmic and heteroplasmic mutations, as well as CEPH pedigrees to study segregation of polymorphic variants, indicated a very high accuracy; none of the previously identified mutations and polymorphisms escaped detection, and no erroneous segregation patterns of polymorphic variants were observed. In addition, two variants were found to be novel mutations when analyzed by sequence analysis. One of these novel mutations was a heteroplasmic mutation in the COXIII gene that was found to segregate to homoplasmy in the next generation. Heteroplasmic mutations as low as 1% of mtDNA could still be detected.

DNA Mutational Analysis↗

PubMed1998

Gait variability and basal ganglia disorders: stride-to-stride variations of gait cycle timing in Parkinson's disease and Huntington's disease.

The basal ganglia are thought to play an important role in regulating motor programs involved in gait and in the fluidity and sequencing of movement. We postulated that the ability to maintain a steady gait, with low stride-to-stride variability of gait cycle timing and its subphases, would be diminished with both Parkinson's disease (PD) and Huntington's disease (HD). To test this hypothesis, we obtained quantitative measures of stride-to-stride variability of gait cycle timing in subjects with PD (n = 15), HD (n = 20), and disease-free controls (n = 16). All measures of gait variability were significantly increased in PD and HD. In subjects with PD and HD, gait variability measures were two and three times that observed in control subjects, respectively. The degree of gait variability correlated with disease severity. In contrast, gait speed was significantly lower in PD, but not in HD, and average gait cycle duration and the time spent in many subphases of the gait cycle were similar in control subjects, HD subjects, and PD subjects. These findings are consistent with a differential control of gait variability, speed, and average gait cycle timing that may have implications for understanding the role of the basal ganglia in locomotor control and for quantitatively assessing gait in clinical settings.

Adult↗

PubMed1998

Interaction of hypoxia and aging in the heart: analysis of high energy phosphate content.

To test the hypotheses that aged myocardium has lower ATP concentration and that a greater ATP hydrolysis during hypoxia exaggerates diastolic dysfunction in aged myocardium, we used 31P NMR spectroscopy to measure ATP and phosphocreatine (PCr) contents combined with heart function at baseline and during hypoxia and reoxygenation in perfused hearts isolated from young adult (3-4 months old) and old (24-25 months old) Fisher 344 rats. At baseline, old hearts had 30% lower heart rate and prevalent supraventricular arrhythmia; they had lower PCr and creatine contents (approximately 30%) but normal ATP content. Hypoxia caused similar decreases in heart rate and rate pressure product in young and old hearts. There was a two-fold increase in left-ventricular end-diastolic pressure (LVEDP) in young adults, but, surprisingly, no change in LVEDP in old hearts. ATP decreased similarly in hearts from young and old rats, but the PCr decrease was two-fold smaller in old hearts during hypoxia. Superimposition of pacing on hypoxic old hearts caused six-fold increase in LVEDP; although utilization of PCr increased, it was still incomplete. We conclude that PCr is incompletely used to maintain ATP level during hypoxia especially in the senescent heart, and that the increase in LVEDP in old hearts cannot be explained solely by changes in indices of bioenergetics.

Adenosine Triphosphate↗

PubMed1998

Oxidative stress induces DNA fragmentation and caspase activation via the c-Jun NH2-terminal kinase pathway in H9c2 cardiac muscle cells.

The aim of this study was to test the hypothesis that oxidative stress induces apoptosis in the H9c2 cardiac muscle cell line, and that signaling via mitogen-activated protein kinase (MAPK) pathways is involved. Three forms of oxidative stress were utilized: the superoxide generator menadione; hydrogen peroxide; or simulated ischemia followed by reperfusion. Relatively low concentrations of menadione (10 micrometer) or H2O2 (250 micrometer) caused maximal DNA fragmentation and caspase activation, both markers for apoptotic cell death, and preferential activation of the c-Jun NH 2-terminal kinase (JNK) and p38 MAPK pathways. In contrast, higher concentrations of menadione or H 2O2 caused less DNA fragmentation, more necrotic cell death and preferential activation of the extracellular signal-regulated kinase (ERK) pathway. Simulated ischemia alone did not induce DNA fragmentation or caspase activation and activated only the p38 MAPK pathway. However, ischemia plus reperfusion resulted in DNA fragmentation, caspase activation, necrotic cell death and activation of all three MAPK pathways. Selective inhibition of the ERK or p38 MAPK pathways (by PD98059 or SB-203580, respectively) had no effect on the extent of oxidative stress-induced DNA fragmentation or caspase activation. In contrast, inhibition of the JNK pathway by transfection of a dominant negative mutant of JNK markedly reduced the extent of DNA fragmentation and caspase activation induced by oxidative stress. In conclusion, these data suggest that the JNK pathway plays an important role in signaling oxidative stress-induced apoptosis of H9c2 cardiac muscle cells.

Animals↗

PubMed1998

Substituted cGMP analogs can act as selective agonists of the rod photoreceptor cGMP-gated cation channel.

Cyclic nucleotide-gated (CNG) channels are expressed in many cell types in both the nervous system and nonexcitable tissues. In order to understand the roles of cGMP-gated channels, and to distinguish actions of cGMP mediated through CNG channels from those through cGMP-dependent protein kinase (G-kinase), several new cGMP analogs were tested for potency as CNG channel agonists. Using Xenopus oocytes expressing the rat rod cGMP-gated ion channel alpha-subunit, we showed that an analog containing a pCPT group at the 8-position, 8-pCPT-cGMP, was 80 times more potent than cGMP and 14 times more potent than 8-Br-cGMP. 8-pCPT-cGMP is the most potent CNG channel agonist so far described and also has the advantages of much better membrane permeability as well as much higher resistance to PDE-hydrolysis, as compared with 8-Br-cGMP. Modification of both 8-Br-cGMP and 8-pCPT-cGMP by introduction of a sulphur atom into the cyclic phosphate group gave smaller changes in agonist efficiency. Both Sp-8-Br-cGMPS and Sp-8-pCPT-cGMPS acted as agonists of CNG channels and are also G-kinase activators. In contrast, Rp-8-Br-cGMPS was a channel agonist, with an EC50 of 173.5 microM, but a G-kinase antagonist with a Ki of 4 microM. Finally, Rp-8-pCPT-cGMPS was a channel agonist and showed additional noncompetitive antagonist activity at higher concentrations. The results suggest that 8-pCPT-cGMPS is a highly potent photoreceptor CNG channel agonist with high membrane permeability and PDE-resistance and furthermore Rp-8-Br-cGMPS can be used to test whether the actions of cGMP are selectively mediated by CNG channels.

Animals↗

PubMed1998

Notation of previous falls in admission record of hospitalized elderly.

To test the hypothesis that a history of falling is underreported by physicians and nurses, we assessed the extent to which previous falls are noted in the admission medical history. A total of 168 community-dwelling and institutionalized elderly adults, > or = 70 years old, were evaluated in the emergency ward of a tertiary care community-based teaching hospital, and admitted to a general medical ward. Physicians' and nurses' emergency ward and admission notes were reviewed for the inclusion of "falls." Within 72 hours of admission, the information provided or omitted in the medical record was confirmed or refuted by face-to-face interview. Follow-up data were gleaned from computer-based records. The sample population consisted of 113 patients, 56% female, with a mean age of 80.7. Seventy-six patients had fallen within the past 10 years: of these, 32 (42%) were Recent Fallers, and 44 (58%) were Multiple Fallers. Review of the medical records revealed that 56 (74%) of the 76 Fallers were not noted to have fallen by the medical staff. Moreover, 15 (47%) of the Recent Fallers and 28 (64%) of the Multiple Fallers were missed. Examination of the nursing notes yielded similar results. In conclusion, elderly patients fall more frequently than recognized. Physicians and/or nurses should include a question regarding falls as part of the routine medical history.

Accidental Falls↗

PubMed1998

Molecular and pharmacological analysis of cyclic nucleotide-gated channel function in the central nervous system.

Most functional studies of cyclic nucleotide-gated (CNG) channels have been confined to photoreceptors and olfactory epithelium, in which CNG channels are abundant and easy to study. The widespread distribution of CNG channels in tissues throughout the body has only recently been recognized and the functions of this channel family in many of these tissues remain largely unknown. The molecular biological and pharmacological properties of the CNG channel family are summarized in order to put in context studies aimed at probing CNG channel functions in these tissues using pharmacological and genetic methods. Compounds have now been identified that are useful in distinguishing CNG channel activated pathways from cAMP/cGMP dependent-protein kinases or other pathways. The ways in which these interact with CNG channels are understood and this knowledge is leading to the identification of more potent and more specific CNG channel subtype-specific agonists or antagonists. Recent molecular and genetic analyses have identified novel roles of CNG channels in neuronal development and plasticity in both invertebrates and vertebrates. Targeting CNG channels via specific drugs and genetic manipulation (such as knockout mice) will permit better understanding of the role of CNG channels in both basic and higher orders of brain function.

Animals↗

PubMed1998

SRF binding to SRE in the rat heart: influence of age.

One important promoter element at the 5' end of the c-fos gene is the serum response element (SRE). SRE is the site of attachment of the 67-kDa protein serum response factor (SRF) and several accessory proteins (Elk1, SAP1, SAP2/NET), termed the ternary complex factors. The binding of SRF to SRE plays an integral role in c-fos transcription and may occur independently of the association of the ternary complex factors. In the current study, we found that SRF protein expression was increased in the hearts of the old vs young adult rats in the basal condition. The hearts of old rats may have posttranslationally modified SRF proteins that are different compared to that of the young adults. The SRF increase was present both in the cytoplasm as well as in the nucleus in the old hearts. To test whether SRF protein levels in response to acute stress might be altered with age, we studied hearts of young adult and old rats during myocardial infarction. The young adult rat hearts responded to acute ischemic stress with an increase in both p62 and p67 SRF. The hearts of the old rats, however, did not exhibit a significant change in SRF protein expression. These findings demonstrate qualitative as well as quantitative age differences in SRF protein levels, both at baseline and following stimulation. The reduced SRF expression in response to acute cardiac ischemic stress in the old rats might contribute to the observed age-related decrease in the induction of immediate early genes such as c-fos in the heart.

Aging↗