Search

The American Journal of Physiology: Regulatory, Integrative & Comparative Physiology has issued a call for papers on the topic of cardiovascular regulation during exercise, specifically focusing on the role of biological sex and the consequences of aging. The editors are seeking original research, short reports, and reviews that explore areas such as autonomic control of circulation, skeletal muscle, cerebral and cardiac blood flow, cardiac regulation, hemodynamic regulation, and thermal challenges. The aim is to better understand the sex-specific differences in cardiovascular responses to exercise and how they change throughout the lifespan. The call also emphasizes the need to consider the effects of aging, age-related diseases, and medications commonly prescribed to older adults on cardiovascular regulation during exercise. The editors encourage researchers to refer to recently published guidelines on the use of sex and gender in cardiovascular research. [Extracted from the article]

The aim of this study was to investigate how aging affects blood flow and structure of the brain. It was hypothesized older individuals would have lower gray matter volume (GMV), resting cerebral blood flow (CBF0), and depressed responses to isometabolic and neurometabolic stimuli. In addition, increased carotid-femoral pulse-wave velocity (PWV), carotid intima-media thickness (IMT), and decreased brachial flow-mediated dilation (FMD) would be associated with lower CBF0, cerebrovascular reactivity (CVR), and GMV. Brain scans (magnetic resonance imaging) and cardiovascular examinations were conducted in young (age = 24 ± 3 yr, range = 22–28 yr; n = 13) and old (age = 71 ± 4 yr; range = 67–82 yr, n = 14) participants, and CBF0, CVR [isometabolic % blood oxygen level-dependent (BOLD) in response to a breath hold (BH)], brain activation patterns during a working memory task (neurometabolic %BOLD response to N-back trial), GMV, PWV, IMT, and FMD were measured. CBF0 and to a lesser extent CVRBH were lower in the old group (P 0.050); however, the increase in the %BOLD response to the memory task was not blunted (P 0.2867). Age-related differential activation patterns during the working memory task were characterized by disinhibition of the default mode network in the old group (P < 0.0001). Linear regression analyses revealed PWV, and IMT were negatively correlated with CBF0, CVRBH, and GMV across age groups, but within the old group alone only the relationships between PWV-CVRBH and IMT-GMV remained significant (P 0.0183). These findings suggest the impacts of age on cerebral % BOLD responses are stimulus specific, brain aging involves alterations in cerebrovascular and possibly neurocognitive control, and arterial stiffening and wall thickening may serve a role in cerebrovascular aging. NEW & NOTEWORTHY Cerebral perfusion was lower in old versus young adults. %Blood oxygen level-dependent (BOLD) responses to an isometabolic stimulus and gray matter volume were decreased in old versus young adults and associated with arterial stiffening and wall thickening. The increased %BOLD response to a neurometabolic stimulus appeared unaffected by age; however, the old group displayed disinhibition of the default mode network during the stimulus. Thus, age-related alterations in cerebral %BOLD responses were stimulus specific and related to arterial remodeling. [ABSTRACT FROM AUTHOR]

We introduce the concept of cardiac neuroautonomic renewability and a method for its quantification. This concept refers to the involuntary nervous system's capacity to improve cardiac control in response to restorative interventions, such as sleep. We used the change in heart rate fragmentation (DHRF), before sleep onset compared with after sleep termination, to quantify the restorative effects of sleep. We hypothesized that the ability to improve cardiac neuroautonomic functionality would diminish with age and be associated with lower risk of major adverse cardiovascular events (MACE). We analyzed the ECG channel of polysomnographic recordings from an ancillary investigation of the Multi-Ethnic Study of Atherosclerosis (MESA). In a cohort of 659 participants (mean ± SD age, 69.7 ± 8.8; 42% male), HRF was significantly (P < 0.001) lower after sleep (before: 74 ± 12%, after: 67 ± 13%). Furthermore, the magnitude of the decrease significantly (P < 0.001) diminished with cross-sectional age. In addition, a larger reduction in HRF following sleep (i.e., higher DHRF) was associated with lower risk of MACE, independent of traditional cardiovascular risk factors and current measures of sleep quality. Specifically, over a mean follow-up period of 6.4 ± 1.6 yr, in which 60 participants had their first MACE, a one-SD (12%) increase in DHRF was associated with a 36% (95% CI: 12%--53%) decrease in the risk of MACE. The results demonstrate the restorative impact of sleep on heart rate control. As such they support the concept of cardiac neuroautonomic renewability and the utility of DHRF for its quantification. [ABSTRACT FROM AUTHOR]

The prevalence of cardiovascular diseases dramatically increases with age; therefore, striving to maintain a physiological heart function is particularly important. Our aim was to study the voluntary exercise-evoked cardioprotective effects in aged male and female rats, from genetic alterations to changes in heart performance. We divided 20-month-old female and male Wistar rats to control and running groups. After the 12-wk-long experimental period, echocardiographic measurements were performed. Afterwards, hearts were either removed for biochemical measurements or mounted into a Langendorff-perfusion system to detect infarct size. The following genes and their proteins were analyzed from heart: catechol-O-methyltransferase (Comt), endothelin-1 (Esm1), Purkinje cell protein-4 (Pcp4), and osteoglycin (Ogn). Recreational exercise caused functional improvements; however, changes were more prominent in males. Cardiac expression of Comt and Ogn was reduced as a result of exercise in aged males, whereas Pcp4 and Esm1 showed a marked overexpression, along with a markedly improved diastolic function. The key result of this study is that exercise enhanced the expression of the Pcp4 gene and protein, a recently described regulator of calcium balance in cardiomyocytes, and suppressed Comt and Ogn gene expression, which has been associated with impaired cardiac function. In addition, as a result of exercise, a significant improvement was observed in the size of infarct elicited by left anterior descending coronary artery occlusion. Our results clearly show that age and sex-dependent changes were both apparent in key proteins linked to cardiovascular physiology. Exercise-moderated fundamental genetic alterations may have contributed to the functional adaptation of the heart. [ABSTRACT FROM AUTHOR]

The aim of the present study was to determine the magnitude of the maximal level of peripheral fatigue attainable (fatigue threshold) during an all-out intermittent isometric knee-extensor protocol in both younger (24 ± 1 yr, n = 12) and older (60 ± 2 yr, n = 12) participants to provide new insights into the effects of aging on neuromuscular function. Participants performed two experimental sessions, in which they performed 60 maximal voluntary contractions (MVCs; 3 s of contraction, 2 s of relaxation). One trial was performed in the unfatigued state (CTRL) and one other following fatiguing neuromuscular electrical stimulation of the quadriceps (FNMES). Peripheral fatigue was quantified via pre/postexercise decrease in quadriceps twitch force (ΔPtw). Critical force (CF) was determined as the mean force output of the last 12 contractions, whereas W0 was calculated as the area above CF. Although FNMES led to a significant decrease in Ptw before performing the 60-MVCs protocol (P = 0.024), ΔPtw was not different between CTRL and FNMES for both the young group (P = 0.491) and the old group (P = 0.523). However, this peripheral fatigue threshold was significantly greater in young versus old participants (ΔPtw =-48 ± 10% vs. -29 ± 13%, respectively, P = 0.028). In CTRL, W0 was 55 ± 13% lower in the old group than in the young group (P < 0.001), but CF was similar (326 ± 10 N vs. 322 ± 12 N, respectively, P = 0.941). ΔPtw was correlated with W0, independently of age (r²= 0.84, P < 0.001). Exercise performance decreases with aging consequent to a lower tolerance to peripheral fatigue. However, the peripheral fatigue threshold mechanism persists with healthy aging and continues to play a protective role in preserving locomotor muscle function during exercise. [ABSTRACT FROM AUTHOR]

Maintenance of the volume and osmolality of body fluids is important, and the adaptive responses recruited to protect against osmotic stress are crucial for survival. The objective of this work was to compare the responses that occur in aging male and female rats during water deprivation. For this purpose, groups of male and female Wistar rats aged 3 mo (adults) or 18 mo (old) were submitted to water deprivation (WD) for 48 h. The water and sodium (0.15 M NaCl) intake, plasma concentrations of oxytocin (OT), arginine vasopressin (AVP), corticosterone (CORT), atrial natriuretic peptide (ANP), and angiotensin II (ANG II) were determined in hydrated and water-deprived animals. In response to WD, old male and female rats drank less water and saline than adults, and both adult and old females drank more water and saline than respective males. Dehydrated old animals displayed lower ANG II plasma concentration and CORT response compared with the respective normohydrated rats. Dehydrated adult males had higher plasma ANP and AVP as well as lower CORT concentrations than dehydrated adult females. Moreover, plasma OT and CORT levels of old female rats were higher than those in the dehydrated old male rats. Relative expression of ANG II type 1 receptor mRNA was decreased in the subfornical organ of adult and old male rats as well as adult female rats in response to WD. In conclusion, the study elucidated the effect of sex and age on responses induced by WD, altering the degree of dehydration induced by 48 h of WD. [ABSTRACT FROM AUTHOR]

Long interspersed element-1 (LINE-1) is a retrotransposon capable of replicating and inserting LINE-1 copies into the genome. Others have reported skeletal muscle LINE-1 markers are higher in older versus younger mice, but data are lacking in other species. Herein, gastrocnemius muscle from male Fischer 344 rats that were 3, 12, and 24 mo old (n = 9 per group) were analyzed for LINE-1 mRNA, DNA, promoter methylation and DNA accessibility. qPCR primers were designed for active (L1.3) and inactive (L1.Tot) LINE-1 elements as well as part of the ORF1 sequence. L1.3, L1.Tot, and ORF1 mRNAs were higher (P < 0.05) in 12/24 versus 3-mo-old rats. L1.3 DNA was higher in the 24-mo-old rats versus other groups, and ORF1 DNA was greater in 12/24 versus 3-mo-old rats. ORF1 protein was higher in 12/24 versus 3-mo-old rats. RNAsequencing indicated mRNAs related to DNA methylation (Tet1) and histone acetylation (Hdac2) were lower in 24 versus 3-mo-old rats. L1.3 DNA accessibility was higher in 24-mo-old versus 3-mo-old rats. No age-related differences in nuclear histone deacetylase (HDAC) activity existed, although nuclear DNA methyltransferase (DNMT) activity was lower in 12/24 versus 3-mo-old rats (P < 0.05). In summary, markers of skeletal muscle LINE-1 activity increase across the age spectrum of rats, and this may be related to deficits in DNMT activity and/or increased LINE-1 DNA accessibility. [ABSTRACT FROM AUTHOR]

Cyclooxygenase (COX) contributes to cutaneous vasodilation and sweating responses; however, the mechanisms underpinning these responses remain unknown. We hypothesized that prostaglandin E1 (PGE1) and E2 (PGE2) (COX-derived vasodilator products) directly mediate cutaneous vasodilation and sweating through nitric oxide synthase (NOS)-dependent mechanisms in young adults. Furthermore, we hypothesized that this response is diminished in older adults, since aging attenuates COX-dependent cutaneous vasodilation and sweating. In 9 young (22 ± 5 yr) and 10 older (61 ± 6 yr) adults, cutaneous vascular conductance (CVC) and sweat rate were evaluated at four intradermal forearm skin sites receiving incremental doses (0.05, 0.5, 5, 50, 500 μM each for 25 min) of PGE1 or PGE2 with and without coadministration of 10 mM Nω-nitro-L-arginine, a nonspecific NOS inhibitor. Nω-nitro-L-arginine attenuated PGE1-mediated increases in CVC at all concentrations in young adults, whereas it reduced PGE2-mediated increases in CVC at lower concentrations (0.05--0.5 µM) in older adults (all P < 0.05). However, the magnitude of the PGE1- and PGE2-mediated increases in CVC did not differ between groups (all P > 0.05). Neither PGE1 nor PGE2 increased sweat rate at any of the administered concentrations for either the young or older adults (all P > 0.05). We show that although cutaneous vascular responsiveness to PGE1 and PGE2 is similar between young and older adults, the cutaneous vasodilator response is partially mediated through NOS albeit via low-to-high concentrations of PGE1 in young adults and low concentrations of PGE2 in older adults, respectively. We also show that in both young and older adults, PGE1 and PGE2 do not increase sweat rate under normothermic conditions. [ABSTRACT FROM AUTHOR]

Skeletal muscle insulin resistance is associated with many common age-related diseases, but moderate calorie restriction (CR) can substantially elevate glucose uptake by insulin-stimulated skeletal muscle from both young and old rats. The current study evaluated the isolated epitrochlearis muscle from ~24.5-mo-old rats that were either fed ad libitum (AL) or subjected to CR (consuming ~65% of ad libitum, AL, intake beginning at ~22.5 mo old). Some muscles were also incubated with MK-2206, a potent and selective Akt inhibitor. The most important results were that in isolated muscles, CR vs. AL resulted in 1) greater insulinstimulated glucose uptake 2) that was accompanied by significantly increased insulin-mediated activation of Akt2, as indicated by greater phosphorylation on both Thr309 and Ser474 along with greater Akt2 activity, 3) concomitant with enhanced phosphorylation of several Akt substrates, including an Akt substrate of 160 kDa on Thr642 and Ser588, filamin C on Ser2213 and proline-rich Akt substrate of 40 kDa on Thr246, but not TBC1D1 on Thr596; and 4) each of the CR effects was eliminated by MK-2206. These data provide compelling new evidence linking greater Akt2 activation to the CR-induced elevation of insulin-stimulated glucose uptake by muscle from old animals. [ABSTRACT FROM AUTHOR]

Proteinrich-supplements are used widely for the management of malnutrition in young and older people. Protein is the most satiating of the macronutrients in young. It is not known how the effects of oral protein ingestion on energy intake, appetite, and gastric emptying are modified by age. The aim of the study was to determine the suppression of energy intake by protein compared with control and underlying gastric-emptying and appetite responses of oral whey protein drinks in eight healthy older men (69-80 yr) compared with eight young male controls (18-34 yr). Subjects were studied on three occasions to determine the effects of protein loads of 30 g/120 kcal and 70 g/280 kcal compared with a flavored water control-drink (0 g whey protein) on energy intake (ad libitum buffet-style meal), and gastric emptying (three-dimensional-ultrasonography) and appetite (0-180 min) in a randomized, double-blind, cross-over design. Energy intake was suppressed by the protein compared with control (P ± 0.034). Suppression of energy intake by protein was less in older men (1 ± 5%) than in young controls (15 ± 2%; P ± 0.008). Cumulative energy intake (meal+drink) on the protein drink days compared with the control day increased more in older (18 ± 6%) men than young (1 ± 3%) controls (P ± 0.008). Gastric emptying of all three drinks was slower in older men (50% gastric-emptying time: 68 ± 5 min) than young controls (36 ± 5 min; P < 0.007). Appetite decreased in young, while it increased in older (P < 0.05). In summary, despite having slower gastric emptying, elderly men exhibited blunted protein-induced suppression of energy intake by whey protein compared with young controls, so that in the elderly men, protein ingestion increased overall energy intake more than in the young men. [ABSTRACT FROM AUTHOR]