scholarly journals Cardiorespiratory fitness through the early lifecourse and attempts to modulate its initial decline

2015 ◽  
Author(s):  
◽  
Ryan Toedebusch
Keyword(s):  
Molecular Mechanisms ◽  
Wheel Running ◽  
Human Life ◽  
Strong Predictor ◽  
Transcriptomic Analysis ◽  
Female Rats ◽  
Chronological Age ◽  
Two Phases ◽  
Running Wheels ◽  
Muscle Gene

There has never been an outcome measure for human health more important than VO2peak, yet we know nothing about the molecular triggers for its decline with aging. Peak aerobic capacity (VO2peak) is a strong predictor of morbidity and mortality. Lifetime-apex VO2peak is the highest value for VO2peak during the life course and declines beginning the 3rd decade of human life. I examined the ability of chronic voluntary wheel running, or 5-weeks of AICAR administration, to delay the chronological age at which the decline of lifetime-apex VO2peak begins and potential underlying molecular mechanisms. Experiment one consisted of female rats with (RUN) and without (NO RUN) running wheels that underwent frequent VO2peak tests beginning at 10-weeks of age and continuing until 27-weeks of age. Lifetime apex-VO2peak occurred at 19 weeks of age in both groups, decreasing thereafter. On average, VO2peak measured across experiment one was [about]25% higher in RUN. Experiment two used the AMPK-agonist AICAR, beginning at 17-weeks of age to test if the chronological age for lifetime-apex VO2peak decline could be shifted to an older age. Two groups of female rats, AICAR (0.5 mg/kg daily) and vehicle (VEH, saline) were used for 5-weeks and all animals were sacrificed at 22-weeks of age. Compared to VEH group, AICAR rats showed significantly higher body weights, muscle weights, heart weights and lower % body fat. Additionally, AICAR was able to delay the initial decline by one-week, from 19- to 20-weeks of age, but was lowered to VEH levels at 22- weeks of age. Transcriptomic analysis of the lateral head of the tricep muscle from experiment one animals revealed mRNA differences in RUN vs. NO RUN, suggesting differing skeletal muscle gene regulation immediately prior to lifetime-apex VO2peak decline. Two phases of life were examined, pre-apex VO2peak (17- to 19-weeks of age) and post-apex (19- to 27-weeks of age). These data indicate that rat wheel running increases VO2peak 25% and is not sufficient to delay the chronological age of lifetime-apex VO2peak decline, whereas AICAR delayed it one week. Transcriptomic analysis of experiment one offers target molecules that play a role in: 1) the causation of the decline occurring at 19-weeks of age, and 2) potential genes and mechanisms contributing to the initiation of decline in lifetime-apex VO2peak.

AMPK agonist AICAR delays the initial decline in lifetime-apex V̇o2 peak, while voluntary wheel running fails to delay its initial decline in female rats

2016 ◽  
Vol 48 (2) ◽  
pp. 101-115 ◽  
Author(s):  
Ryan G. Toedebusch ◽  
Gregory N. Ruegsegger ◽  
Joshua F. Braselton ◽  
Alexander J. Heese ◽  
John C. Hofheins ◽  
...  
Keyword(s):  
Protein Concentration ◽  
Molecular Mechanisms ◽  
Outcome Measure ◽  
Wheel Running ◽  
Female Rats ◽  
Peak Oxygen Consumption ◽  
Chronological Age ◽  
Primary Hypothesis ◽  
Running Wheels ◽  
Voluntary Wheel

There has never been an outcome measure for human health more important than peak oxygen consumption (V̇o2 peak), yet little is known regarding the molecular triggers for its lifetime decline with aging. We examined the ability of physical activity or 5 wk of 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) administration to delay the initial aging-induced decline in lifetime-apex V̇o2 peak and potential underlying molecular mechanisms. Experiment 1 consisted of female rats with (RUN) and without (NO RUN) running wheels, while experiment 2 consisted of female nonrunning rats getting the AMPK agonist AICAR (0.5 mg/g/day) subcutaneously for 5 wk beginning at 17 wk of age. All rats underwent frequent, weekly or biweekly V̇o2 peak tests beginning at 10 wk of age. In experiment 1, lifetime-apex V̇o2 peak occurred at 19 wk of age in both RUN and NO RUN and decreased thereafter. V̇o2 peak measured across experiment 1 was ∼25% higher in RUN than in NO RUN. In experiment 2, AICAR delayed the chronological age observed in experiment 1 by 1 wk, from 19 wk to 20 wk of age. RUN and NO RUN showed different skeletal muscle transcriptomic profiles both pre- and postapex. Additionally, growth and development pathways are differentially regulated between RUN and NO RUN. Angiomotin mRNA was downregulated postapex in RUN and NO RUN. Furthermore, strong significant correlations to V̇o2 peak and trends for decreased protein concentration supports angiomotin's potential importance in our model. Contrary to our primary hypothesis, wheel running was not sufficient to delay the chronological age of lifetime-apex V̇o2 peak decline, whereas AICAR delayed it 1 wk.

Diet-induced hyperphagia in the rat is influenced by sex and exercise

2004 ◽  
Vol 287 (5) ◽  
pp. R1080-R1085 ◽  
Author(s):  
Lisa A. Eckel ◽  
Shelley R. Moore
Keyword(s):  
Estrous Cycle ◽  
Wheel Running ◽  
Caloric Intake ◽  
Female Rats ◽  
Male Rats ◽  
Milk Diet ◽  
Daily Caloric Intake ◽  
Running Wheels

Caloric intake is increased in rats fed a diet containing greater fat or sugar than that found in laboratory chow. Because such diet-induced hyperphagia has been studied primarily in sedentary male rats, our goal here was to investigate the effects of sex and exercise on caloric intake of a diet (chow supplemented with sweet milk) chosen for its ability to stimulate hyperphagia. Rats were housed individually in cages that provided access to running wheels, and daily caloric intake of chow alone and then chow plus sweet milk was monitored during sedentary and active conditions. In sedentary rats, chow intake was greater in males compared with females. Wheel running produced similar decreases in chow intake in both sexes. Availability of the chow plus milk diet increased caloric intake compared with that observed in chow-fed rats. This diet-induced hyperphagia was significantly greater in sedentary females (35.7 ± 3.1% increase) relative to sedentary males (9.1 ± 2.2% increase). In addition, 35% of sedentary females consuming the chow plus milk diet developed estrous cycle disruptions. Wheel running decreased intake of the chow plus milk diet in both sexes. In active males, diet-induced hyperphagia was abolished; caloric intake was reduced to that observed during chow feeding. In active female rats, diet-induced hyperphagia was attenuated but not abolished; caloric intake of the chow plus milk diet remained greater than that observed during chow feeding. We conclude that female rats are more vulnerable than male rats to this form of diet-induced hyperphagia.

scholarly journals Daily Lifestyle and Cutaneous Malignancies

2021 ◽  
Vol 22 (10) ◽  
pp. 5227
Author(s):  
Yu Sawada ◽  
Motonobu Nakamura
Keyword(s):  
Cell Carcinoma ◽  
Molecular Mechanisms ◽  
Skin Diseases ◽  
Human Life ◽  
Lifestyle Factors ◽  
Merkel Cell ◽  
Fundamental Part ◽  
Skin Cancers ◽  
Beneficial Impact ◽  
The Relationship

Daily lifestyle is a fundamental part of human life and its influence accumulates daily in the human body. We observe that a good daily lifestyle has a beneficial impact on our health; however, the actual effects of individual daily lifestyle factors on human skin diseases, especially skin cancers, have not been summarized. In this review, we focused on the influence of daily lifestyle on the development of skin cancer and described the detailed molecular mechanisms of the development or regulation of cutaneous malignancies. Several daily lifestyle factors, such as circadian rhythm disruption, smoking, alcohol, fatty acids, dietary fiber, obesity, and ultraviolet light, are known to be associated with the risk of cutaneous malignancies, malignant melanoma, squamous cell carcinoma, basal cell carcinoma, and Merkel cell carcinoma. Although the influence of some daily lifestyles on the risk of skin cancers is controversial, this review provides us a better understanding of the relationship between daily lifestyle factors and skin cancers.

Long-Term Exercise Training Selectively Alters Serum Cytokines Involved in Fever

2009 ◽  
Vol 10 (4) ◽  
pp. 374-380 ◽  
Author(s):  
Pamela Johnson Rowsey ◽  
Bonnie L. Metzger ◽  
John Carlson ◽  
Christopher J. Gordon
Keyword(s):  
Exercise Training ◽  
Core Temperature ◽  
Binding Capacity ◽  
Serum Zinc ◽  
Female Rats ◽  
Chronic Exercise ◽  
Serum Cytokines ◽  
Tnf Α ◽  
Running Wheels

Long-term exercise training selectively alters serum cytokines involved in fever. Chronic exercise training has a number of effects on the immune system that may mimic the physiological response to fever. Female rats that voluntarily exercise on running wheels develop an elevated daytime core temperature after several weeks of training. It remains to be seen whether the elevation in daytime temperature involves inflammatory patterns characteristic of an infectious fever. We assessed whether chronic exercise training in the rat would alter levels of cytokines involved in fever. Female Sprague Dawley rats at 45 days of age weighing 90—110 g were divided into two groups (exercise and sedentary) and housed at an ambient temperature of 22°C. Interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-α), iron, and zinc levels were analyzed. Rats underwent 8 weeks of exercise on running wheels. Exercise led to altered levels of some key cytokines that are involved in fever. Exercise animals had significantly higher IL-1β levels and lower IL-10 levels compared to sedentary animals. Although IL-6 levels were slightly lower in the exercise animals, these levels were not significantly affected by training. TNF-α activity was similar in the two groups. Training also led to a slight increase in serum zinc and decrease in serum unsaturated iron binding capacity (UIBC). The data suggest that chronic exercise training evokes immune responses that mimic some, but not all, aspects of fever. This may explain why exercise leads to elevated daytime core temperature.

Gonadal hormones organize and modulate the circadian system of the rat

1981 ◽  
Vol 241 (1) ◽  
pp. R62-R66 ◽  
Author(s):  
H. E. Albers
Keyword(s):  
Testosterone Propionate ◽  
Wheel Running ◽  
Activity Rhythm ◽  
Gonadal Hormones ◽  
Circadian System ◽  
Female Rats ◽  
Constant Darkness ◽  
Before And After ◽  
Free Running ◽  
Free Running Period

The circadian wheel-running rhythms of gonadectomized adult male, female, and perinatally androgenized female rats, maintained in constant darkness, were examined before and after implantation of Silastic capsules containing cholesterol (C) or estradiol-17 beta (E). The free-running period of the activity rhythm (tau) before capsule implantation tended to be shorter in animals exposed to perinatal androgen. Administration of C did not reliably alter tau in any group. E significantly shortened tau in 100% of females injected with oil on day 3 of life. In females, injected with 3.5 micrograms testosterone propionate on day 3, and males, E shortened or lengthened tau, with the direction and magnitude of this change in tau inversely related to the length of the individual's pretreatment tau. These data indicate that the presence of perinatal androgen does not eliminate the sensitivity of the circadian system of the rat to estrogen, since estrogen alters tau in a manner that depends on its pretreatment length.

Left ventricle transcriptomic analysis reveals connective tissue accumulation associates with initial age-dependent decline in V̇o2peak from its lifetime apex

2017 ◽  
Vol 49 (1) ◽  
pp. 53-66 ◽  
Author(s):  
Gregory N. Ruegsegger ◽  
Ryan G. Toedebusch ◽  
Joshua F. Braselton ◽  
Thomas E. Childs ◽  
Frank W. Booth
Keyword(s):  
Connective Tissue ◽  
Left Ventricle ◽  
Wheel Running ◽  
Protein Translation ◽  
Transcriptomic Analysis ◽  
Peak Oxygen Consumption ◽  
Activity Levels ◽  
Tissue Development ◽  
Female Wistar Rats ◽  
Better Than

Peak oxygen consumption (V̇o2peak) strongly predicts morbidity and mortality better than other established risk factors, yet mechanisms associated with its age-associated decline are unknown. Our laboratory has shown that V̇o2peak first begins to decrease at the same age of 19–20 wk in both sedentary and wheel-running, female Wistar rats (Toedebusch et al., Physiol Genomics. 48: 101–115, 2016). Here, we employed a total systemic approach using unsupervised interrogation of mRNA with RNA sequencing. The purpose of our study was to analyze transcriptomic profiles from both sedentary (SED) and wheel-running (RUN) conditions as a strategy to identify pathways in the left ventricle that may contribute to the initial reductions in V̇o2peak occurring between 19 and 27 wk of age. Transcriptomic comparisons were made within both SED and RUN rats between 19 and 27 wk ( n = 5–8). Analysis of mRNAs shared in SED and RUN between 19 and 27 wk found 17 upregulated (e.g., Adra1d, Rpl17, Xpo7) and 8 downregulated (e.g., Cdo1, Ctfg, Sfrp1) mRNAs, at 19 wk, respectively. Furthermore, bioinformatics analysis of mRNAs common to SED and RUN produced networks suggestive of increased connective tissue development at 27 vs. 19 wk. Additionally, Ctfg mRNA was negatively associated with V̇o2peak in both SED and RUN ( P < 0.05). In summary, transcriptomic analysis revealed mRNAs and networks associated with increased connective tissue development, decreased α-adrenergic activity, and decreased protein translation in the left ventricle that could, in part, potentially influence the initiation of the lifelong reduction in V̇o2peak, independent of physical activity levels.

scholarly journals 17-β-Estradiol Induces Heat Shock Proteins in Brain Arteries and Potentiates Ischemic Heat Shock Protein Induction in Glia and Neurons

2002 ◽  
Vol 22 (2) ◽  
pp. 183-195 ◽  
Author(s):  
Aigang Lu ◽  
Rui-qiong Ran ◽  
Joseph Clark ◽  
Melinda Reilly ◽  
Alex Nee ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Hippocampal Neurons ◽  
Molecular Mechanisms ◽  
Female Rats ◽  
Male Rats ◽  
Western Blots ◽  
Male And Female ◽  
Male And Female Rats

Estradiol reduces brain injury from many diseases, including stroke and trauma. To investigate the molecular mechanisms of this protection, the effects of 17-β-estradiol on heat shock protein (HSP) expression were studied in normal male and female rats and in male gerbils after global ischemia. 17-β-Estradiol was given intraperitoneally (46 or 460 ng/kg, or 4.6 μg/kg) and Western blots performed for HSPs. 17-β-Estradiol increased hemeoxygenase-1, HSP25/27, and HSP70 in the brain of male and female rats. Six hours after the administration of 17-β-estradiol, hemeoxygenase-1 increased 3.9-fold (460 ng/kg) and 5.4-fold (4.6 μg/kg), HSP25/27 increased 2.1-fold (4.6 μg/kg), and Hsp70 increased 2.3-fold (460 ng/kg). Immunocytochemistry showed that hemeoxygenase-1, HSP25/27,and HSP70 induction was localized to cerebral arteries in male rats, possibly in vascular smooth muscle cells. 17-β-Estradiol was injected intraperitoneally 20 minutes before transient occlusion of both carotids in adult gerbils. Six hours after global cerebral ischemia, 17-β-estradiol (460 ng/kg) increased levels of hemeoxygenase-1 protein 2.4-fold compared with ischemia alone, and HSP25/27 levels increased 1.8-fold compared with ischemia alone. Hemeoxygenase-1 was induced in striatal oligodendrocytes and hippocampal neurons, and HSP25/27 levels increased in striatal astrocytes and hippocampal neurons. Finally, Western blot analysis confirmed that estrogen induced heat shock factor-1, providing a possible mechanism by which estrogen induces HSPs in brain and other tissues. The induction of HSPs may be an important mechanism for estrogen protection against cerebral ischemia and other types of injury.

scholarly journals Quantitative Proteomics Reveals that GmENO2 Proteins Are Involved in Response to Phosphate Starvation in the Leaves of Glycine max L.

2021 ◽  
Vol 22 (2) ◽  
pp. 920
Author(s):  
Ling Cheng ◽  
Wanling Min ◽  
Man Li ◽  
Lili Zhou ◽  
Chuan-Chih Hsu ◽  
...  
Keyword(s):  
Glycine Max ◽  
Molecular Mechanisms ◽  
Human Life ◽  
Phosphate Starvation ◽  
Limiting Factor ◽  
Transcriptional Level ◽  
Label Free ◽  
Promoter Regions ◽  
Glycine Max L ◽  
Soybean Plants

Soybean (Glycine max L.) is a major crop providing important source for protein and oil for human life. Low phosphate (LP) availability is a critical limiting factor affecting soybean production. Soybean plants develop a series of strategies to adapt to phosphate (Pi) limitation condition. However, the underlying molecular mechanisms responsible for LP stress response remain largely unknown. Here, we performed a label-free quantification (LFQ) analysis of soybean leaves grown under low and high phosphate conditions. We identified 267 induced and 440 reduced differential proteins from phosphate-starved leaves. Almost a quarter of the LP decreased proteins are involved in translation processes, while the LP increased proteins are accumulated in chlorophyll biosynthetic and carbon metabolic processes. Among these induced proteins, an enolase protein, GmENO2a was found to be mostly induced protein. On the transcriptional level, GmENO2a and GmENO2b, but not GmENO2c or GmENO2d, were dramatically induced by phosphate starvation. Among 14 enolase genes, only GmENO2a and GmENO2b genes contain the P1BS motif in their promoter regions. Furthermore, GmENO2b was specifically induced in the GmPHR31 overexpressing soybean plants. Our findings provide molecular insights into how soybean plants tune basic carbon metabolic pathway to adapt to Pi deprivation through the ENO2 enzymes.

Effects of exercise on insulin distribution and action in testosterone-treated oophorectomized female rats

2000 ◽  
Vol 88 (6) ◽  
pp. 2116-2122 ◽  
Author(s):  
Maria Niklasson ◽  
Peter Daneryd ◽  
Peter Lönnroth ◽  
Agneta Holmäng
Keyword(s):  
Insulin Resistance ◽  
Physical Exercise ◽  
Insulin Action ◽  
Female Rats ◽  
Control Group ◽  
Free Access ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Severe Insulin Resistance ◽  
Ovx Rats ◽  
Running Wheels

Administration of testosterone (T) to oophorectomized (Ovx) female rats is followed by severe insulin resistance, localized to postreceptor cellular events in the muscle. In this study, intervention by exercise was introduced to examine whether circulatory adaptations are involved in insulin resistance. Two groups of Ovx rats were studied: one group was given T (Ovx+T); another group had free access to running wheels (Ovx+T+Ex). In addition, one control group (sham operated) was studied. Insulin sensitivity was measured with the euglycemic hyperinsulinemic clamp technique (submaximal) for 150 min. Muscle interstitial glucose and insulin concentrations were measured by microdialysis. The measurements showed that, in Ovx+T rats, the onset of insulin action was significantly ( P < 0.05) slower during the first 95 min of the clamp compared with that in Ovx+T+Ex and controls. Muscle interstitial concentrations of insulin but not glucose were lower in both Ovx+T and Ovx+T+Ex rats than in controls throughout the clamp. It was concluded that physical exercise prevented the slow onset of insulin action in Ovx+T rats without changing the distribution time of muscle interstitial insulin. The results indicate that hyperandrogenicity is characterized by delayed muscle insulin action. Physical exercise reverses these defects without any beneficial effect on muscle interstitial insulin concentrations.

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