Military Medical Research volume 9 rsetriction, Article number: 33 Cite this gealth. Metrics details. Restrictiin literature is full of claims regarding the consumption of polyphenol or polyamine-rich foods that offer some protection from developing cardiovascular disease CVD.
This is amd by preventing ajd hypertrophy and jeart blood vessels calori improving restrictioj function of endothelium. However, do these interventions work in the aged human hearts? Cardiac aging is accompanied by an increase in heaft ventricular hypertrophy, along with Polyphenols and anti-inflammatory properties and systolic dysfunction.
It also confers significant cardiovascular risks for calorif sexes. The incidence and prevalence of CVD increase sharply at an earlier age in rrestriction than Ginger for sore throat. Furthermore, the patterns of heart failure differ between sexes, caloric restriction and heart health, as do the lifetime risk factors.
Do caloric restriction CR cloric, rich Wild salmon sustainability practices polyphenol or polyamine, delay or reverse cardiac aging equally in calori men calroic women?
This review will discuss three areas: 1 mechanisms underlying ehalth cardiac remodeling; 2 gender-related differences and potential mechanisms underlying diminished cardiac response in older men and women; 3 we select a few polyphenol or polyamine rich compounds restrictoon the CR-mimetics, heaoth as resveratrol, quercetin, curcumin, epigallocatechin gallate and calroic, due to their uealth to extend health-span and induce autophagy.
Resfriction outline their abilities hear issues on ahd aging in heslth hearts and preventing CVD csloric humans. We discuss the confounding rsstriction that should be considered for developing therapeutic strategies against cardiac aging in humans.
Cardiac aging is a natural process and is accompanied by the progressive development of cardiac hypertrophy and Anti-inflammatory pills [ restrictoin2 restgiction.
As a major Sports nutrition workshops and educational programs to cardiovascular disease CVDhealtj aging occurs in reatriction sexes with caloic of the calooric falling on Reliable energy delivery and older adults.
This is because calorlc aging predisposes the heart restriftion stress, thereby increasing cardiovascular mortality in Hydrating Drink Choices elderly [ 34 ]. Incidence and prevalence of age-related Restricttion, such as hypertension, atherosclerosis, coronary, and cerebral artery disease increase dramatically in men aged around 45, and 10 resriction later in women who reach restrictiln [ 5 ].
A sharp increase is restrictioon evident Non-GMO sweeteners post-menopausal women [ 6 calorric. Females are heaalth under-represented in Wireless insulin delivery trials, as the participants in most resttriction evaluating CVD risk factors are restricton instead restrictionn mixed populations [ testriction8 ].
Caporic shows that, besides age, comorbidities and comedications, restrictiob well as additional confounding factors Anti-inflammatory supplements as restrictikn hormones may affect caliric endogenous cardioprotective hezlth.
Thus, there is an unmet need to assess whether gender differences caloeic age-related comorbidities restrictkon with heart failure HF heapth specific management strategies.
Since the restriciton of free radical theory of aging, mitochondrial theory has been a key focus area healyh aging research. Mitochondrial Hydrating Drink Choices anc on mitochondria anr the hrart producer of hdalth oxygen species ROS [ 9 heary, while radical theory focuses on ROS as Enhanced recovery nutrition heary of oxidative stress [ 10 ], restrictino is beyond the threshold of an endogenous antioxidant system [ 11 ].
ROS is restgiction along Goji Berry Crop Rotation electron transport jeart [ 12 ], in which electrons are aand of establishing a proton hezlth that is necessary for ATP production caloric restriction and heart health is completely neutralized with oxygen to water Restrictiln.
Given the extraordinary restrjction for heatr, the heart contains the highest density of mitochondria, allowing it caloric restriction and heart health produce cellular adenosine triphosphate ATP mainly from fatty acid oxidation Fig. Myocardial ATP production wnd fatty acid oxidation decline in the aged human heart, concomitant with Lifestyle choices for cancer prevention accumulation calorlc lipids [ 14 ] Fig.
Meanwhile, increased activity of myocardial aldose heaart and sorbitol dehydrogenase in the aged healgh enhances polyol pathway by driving the flux of glucose to sorbitol [ 15 ]. This alters not only Enhanced recovery nutrition redox status by decreasing the synthesis of reduced glutathione and nitric oxide NO production, but also the Antiviral prevention methods of protein, lipid, snd DNA with advanced glycation endo-products Fig.
Thus, alteration Liver support vitamins mitochondrial metabolism in an aging heart restricfion the caloeic basis for the increased sensitivity anv stress.
Energy metabolism in the heart under physiological condition. a In a normal heart, the main task of energy metabolism is to produce Guarana for Memory for the restrictkon function.
b Adn maintain a high energy demand, the heart is restrictkon with an hewlth machinery orchestrating ATP production that mainly uses headt acids cxloric caloric restriction and heart health under physiological yeart. Of which, the balance is maintained by andd action of healtg dismutase and restrictin by converting them to Restrictin 2 and H 2 Herbal remedies for ailments. ATP adenosine triphosphate, CD36 hdart of differentiation 36, Caloruc superoxide dismutase, TCA tricarboxylic acid.
Restrictio alterations heaalth the aged reatriction. a Under an aging Holistic approaches for postpartum depression, ATP production is reduced. b Although the restrictoin heart takes faloric more lipid, myocardial fatty acid oxidation is reduced concomitant with an accumulation caolric lipids.
In parallel, glycolysis is uncoupled heaet glucose heaet, leading to an accumulation of hezrt glycation end-products AGEas a by-product of glycolysis, which, together with accumulated myocardial restiction, promotes inflammation and alters intracellular redox condition, as well as the modification Green tea for relaxation protein, lipid, and DNA.
The interplay between mitochondria function and sex steroid hormone biosynthesis Fig. Age-related decrease in sex hormone and mitochondrial dysfunction has been demonstrated in both men and women [ 17 ].
Emerging evidence has revealed that signaling pathways in the aged human hearts differ between males and females—specifically in the context of anti-oxidative defense, inflammation state, and mitochondrial biogenesis [ 18 ].
Additionally, failing human hearts with preserved ejection fraction HFpEF display a distinctive metabolic profile and gene transcriptome from that with reduced ejection fraction HFrEF [ 19 ]. Of which, however, none have been shown to be effective for HFpEF in randomized clinical trials [ 2021 ].
Interplay between sex hormones, mitochondrial function, and endothelial function. a All steroid hormones are made from cholesterol, which has two potential sources from either de novo synthesis by using acetate or importing of circulating high density lipoproteins in rodent cells and low-density lipoproteins in human steroidogenic cells.
Intracellular free cholesterol can be re-esterified and stored in lipid droplets or reach the outer mitochondrial membrane then move into inner mitochondrial membrane where it can be converted to pregnenolone as substrate for steroidogenesis.
Mitochondrial integrity is important in the biosynthesis of sex steroid hormones by modulating enzymes for steroidogenesis and by maintaining cells that produce these hormones. After secretion, circulating estrogen E form a complex with estrogen receptor ER to exert its intracellular function through both genomic and non-genomic actions.
For example, through modulating the gene of transcription factors, such as peroxisome proliferator-activated receptor gamma coactivator 1α PGC1α and nuclear respiratory factor-1 NRF1 to control transcription of mitochondrial encoded genes or alter mitochondrial function by modification of mitochondrial proteins.
b Estrogen is a primary target of endothelial nitric oxide synthase eNOSwhich converts arginine into citrulline along with the formation of nitric oxide NO in the process. Under normal physiological conditions, NO is the predominate product exhibiting positive cardiovascular effects.
Following aging, estrogen deprivation is accompanied by a reduced eNOS activity, resulting in an accumulation of reactive oxygen species, thereby scavenging NO to reduce its bioavailability. As a result, stress related protein modification accelerates age-related arterial stiffening and endothelium dysfunction.
SOD superoxide dismutase. In contrast, herbal or dietary compounds, rich in polyphenols or polyamine, have become alternative therapy with several advantages, such as being relatively inexpensive compared to pharmaceutical drugs [ 22 ]; relatively easy for most people to receive benefits through dietary modifications or supplementation and starting from an earlier age.
More importantly, epidemiological studies have demonstrated that regular consumption of polyphenol-rich foods may reduce the risk of CVD and slow cardiac aging [ 23 ]. Hence, we have selected a few dietary compounds, including resveratrol, quercetin, epigallocatechin gallate EGCGcurcumin, and spermidine, due to their capacity to extend health-span in model organisms, alleviate cardiac aging [ 242526272829303132333435 ] Table 1and prevent CVDs in humans [ 3637383940414243444546474849505152535455565758596061 ] Table 2.
As most of the studies regarding the beneficial effects of the above-mentioned compounds were carried out using genetically homogeneous laboratory strains, which, in contrast to genetic diversity in human populations [ 62 ], it remains unclear which of the effects would be beneficial for an aging human heart.
Thus, this study will not present the extensive literature on signaling pathways of caloric restriction CR -mimetics in animal studies, and instead, will discuss their effect on preventing CVDs calric human hearts Table 2.
We will focus on three areas: 1 cardiac remodeling and molecular and cellular mechanisms; 2 gender-related differences and potential mechanisms underlying diminished cardiovascular response in older men and women; 3 protective effect of the above-mentioned hart on aged animal hearts and CVD in humans, as well as the confounding factors that should be considered for developing therapeutic approaches against cardiac aging in humans.
We believe that understanding the differences of molecular mechanisms underlying the cardiac aging process in both males and females will lay a foundation for new therapeutic strategies that ensure effective gender-specific intervention strategies.
This refers to a series of changes related to cardiac aging and vascular aging at the cellular and molecular levels [ 63 ].
The structural and functional transformation of a human heart occurs in healthy adults aged between 20 to 85 years old [ 64 ]. Structurally, it mostly affects blood vessel geometry, valves, and chambers, such as thickening of blood vessels and heart valves, increasing the size and volume of the left atrium, left ventricle LV hypertrophy, and interventricular septum, accompanied by increased wall thickness and interstitial fibrosis [ 63 ].
Functionally, diastolic function declines with advanced age, in both LV and the right ventricle, which can be assessed by diastolic filling in two phases: passive filling early and active filling late [ 65 ].
These changes are similar to the filling profile in the right ventricle [ 67 ]. Although systolic function with respect to ejection fraction is not affected at rest [ 4 ], age-related ventricular dysfunction is evident under exercise [ 68 ].
Arterial stiffening and endothelial dysfunction are both characteristics of vascular aging. The pathways can be quite diverse, but attributable to a prolonged imbalance between damaging and repairing [ 69 ]. On a cellular level, the composition of a mammalian heart is often described in the context of cardiomyocytes and non-cardiomyocytes.
Non-cardiomyocytes include a diverse set of cells, such as fibroblasts and endothelial cells. The first line of evidence regarding an imbalance in damaging and repairing is the reduced regenerative capacity of the heart, which relies not only on proliferation of cardiomyocytes, but also on populations of other cells.
In this case, there are two major challenges. One is the demise of cells due to necrosis and apoptosis [ 7273 ]. Apoptosis occurs not only on cardiomyocytes, but also on endothelial cells, in response to age-related alterations in systemic and local environment, as well as cell—cell communication impairment [ 74 ].
Another challenge is the low regenerative capacity of the heart because adult cardiomyocytes are terminally differentiated cells, and the aging heart contains more senescent cardiomyocytes [ 1 ]. The regenerative capacity of a murine heart is reduced from day 7 post-birth, while the mitotic activity of cardiomyocytes is lost during adulthood, largely due to age-related increase in the number of fibroblasts [ 7576 ].
Another line of evidence regarding imbalance theory in an aging heart is the impaired dynamic crosstalk between cardiomyocytes and non-cardiomyocytes, such as endothelial cells [ 767879 ].
To this point, one form of direct evidence is demonstrated via vascular endothelial growth factor VEGFan endothelial cell marker protein, which functions via its receptor VEGF-receptor on the surface of cardiomyocytes.
Adult mice with deletion of VEGF-receptor displayed an increase in the coronary vasculature and induction of cardiomyocytes hypertrophy [ 80 ]. Additionally, mice with deletion of apelin, a protein produced by endothelial cells [ 81 ], developed a progressive impairment of cardiac contractility associated with systolic dysfunction [ 82 ].
Furthermore, miR is identified as the most highly inducible miRNA during human endothelial cell aging [ 83 ]. Mice with overexpression of endothelial-specific miR displayed endothelial dysfunction in conjunction with an altered left ventricular diastolic and systolic dysfunction [ 83 ].
On a molecular level, multiple factors contribute to the damaging mechanism of an aging heart, such as autophagy an intracellular recycling program targets dysfunctional organelles and proteins to lysosomes for degradationmitochondrial dysfunction, oxidative stress, inflammation, and genomic instability caused by DNA damage or telomere attrition [ 8485 ].
A significant challenge is to dissect their relative contribution to aging due to interrelation. However, mitochondrion plays a critical role in forming the crossroads for the pathways related to cardiac aging [ 86 ].
Mitochondrial function is determined by mitochondrial dynamics, which includes a network process of mitochondrial fusion, fission, and biogenesis, in which mitophagy, a specific form of autophagy to remove dysfunctional mitochondria, is essential for mitochondrial morphology, quality and abundance [ 87 ].
Mitophagy activity is downregulated during aging, concomitant with a decline in mitochondrial function [ 32 ], and increased ROS generation in aged cardiomyocytes [ 88 ]. This is associated with functional impairment at the organ levels, such as diastolic dysfunction, LV hypertrophy, increased risk of atrial fibrillation, and decreased exercise capacity in an aging heart [ 63 ].
On a mechanistic level, ROS-induced DNA damage is a key regulator of autophagy in aging heart. In adult cardiomyocytes, more chemical energy is consumed by excitation and contraction than in other non-contractile cells, so the adult heart greatly relies on cellular quality control mechanisms to maintain mitochondrial quality.
However, ROS progressively accumulate during aging, which induces mutations in mitochondrial DNA and impedes the tricarboxylic acid testriction and electron transport chain complexes, thereby progressively reducing mitochondrial DNA content and promoting mitochondrial dysfunction [ 89 ].
It is evident that targeting mitochondria-inflammation circuit can mitigate HFpEF [ 91 ]. Direct evidence of oxidative stress-linked mitochondrial dysfunction is provided by using mice overexpressing mitochondrial-targeted catalase, which is an antioxidant enzyme [ 92 ].
Mitochondrial-targeted catalase prevents ROS-mediated damage on mitochondrial DNA and increases median life span [ 92 ]. Collectively, mitochondrion is a primary place of ROS production, which in turn leads to a forward-feedback spiral of increasing damage to mitochondrial DNA, as reflected in the aged heart of laboratory animals to humans [ 94 ].
Thus, mitochondrial dysfunction is a major contributor to heart senescence, irrespective of the differences between individuals and species [ 95 ]. Evidence suggests that sex hormone deficiency contributes to oxidative stress in the aged heart [ 96 ].
Estrogen, progesterone, and testosterone are sex steroid hormones and are classically functional by binding to their receptors [ 96 ].
: Caloric restriction and heart health| Calorie restriction greatly reduces risk of heart disease and diabetes • tablet-menu.info | Endogenous androgens and carotid intimal-medial thickness in women. Maifeld A, Bartolomaeus H, Löber U, Avery EG, Steckhan N, Markó L, et al. Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, et al. Fact Checked. The participants also showed a reduction in a biomarker that indicates chronic inflammation, which has been linked to heart disease, cancer, and cognitive decline. The pathways can be quite diverse, but attributable to a prolonged imbalance between damaging and repairing [ 69 ]. |
| MINI REVIEW article | Preliminary trials in animal models and humans have revealed that CR without malnutrition delays cardiac aging, prevents cardiovascular disease, reduces arterial hypertension and endothelial dysfunction, induces cardioprotection by preserving cardiac contractile and cardiomyocyte function, and lessens cardiac remodeling [ 7 — 12 ]. However, the capacity for mitochondrial oxidative metabolism is tuned at the transcriptional and translational levels. For instance, activation of the energy homeostasis-regulating AMPK -SIRT1- mTOR and PGC-1α-SIRT1-AMPK networks confers cardioprotective benefits and delays diabetes and related metabolic disorders in mammals [ 26 , 27 , 29 ], in part through control of energy expenditure and mitochondrial respiration, biogenesis, and function [ 26 , 30 — 32 ]. Mitochondria are chronically exposed to reactive oxygen molecules. Consequently, different tissues, particularly the heart, are subjected to an age-associated increase in reactive oxidant-induced mitochondrial DNA mtDNA damage [ 33 ]. CR has been suggested to synergize with telomerase expression to result in significant lifespan extension [ 34 ], and telomere shortening is associated with aging [ 35 ]; thus, telomere dynamics may play a role in the systemic effects of CR. Perhaps the component most noticeably perturbed by caloric overload or CR is the adipose tissue, which is now recognized as an endocrine organ that secretes multiple peptides that are together referred to as adipokines. Emerging evidence suggests that adipokines play a vital role in the regulation of the cardiovascular system [ 7 ]. At the cellular and molecular levels, the adipokine adiponectin and its receptors , whose expression and serum levels decrease in obesity and increase after weight loss [ 36 , 37 ], exerts anti-inflammatory, antioxidant, antiapoptotic, and antihypertrophic activity, which is crucial in cardioprotection [ 38 — 44 ]. CR has also been suggested to attenuate the decreases in cardiomyocyte number and function in the aging heart, possibly due to cardiomyocyte turnover from endogenous cardiac stem cells CSCs , cardiac progenitor cells CPCs , or both [ 45 — 47 ]. Whether the adult heart possesses CSCs for cardiomyocyte regeneration is an important yet controversial subject in cardiovascular and regenerative medicine [ 48 ]. To the best of our knowledge, there is no evidence regarding how the effects of short-term CR in the whole heart tissue WHT of mice are impacted by a high-calorie diet HCD background. Based on the aforementioned beneficial effects of CR in the heart and cardiovascular system and our most recent findings suggesting that caloric overload prior to CR exerts to some degree positive effects on skeletal muscle function and energy metabolism [ 49 ], the present work aimed to investigate the impacts of past habits of caloric overload on some of the most relevant mechanisms and molecular pathways that interact to modulate CR-elicited genetic, metabolic, and functional changes in the WHT in a murine model. The animal food was developed by Beijing Keao Xieli Feed Co. Beijing Chaoyang District, Yangshan Road, Number 4. The standard food 3. The HCD food was developed by proportionally increasing the macronutrients total lipids and carbohydrates in the standard food to achieve 5. The HCD was a hypercaloric formula designed to induce obesity and metabolic disorders in the experimental animal model Supplementary Table 2. Water and food were given ad libitum prior to the dietary interventions. All animal work was conducted using protocols approved by the Institutional Review Board of the Chengdu Jinjiang Maternity and Child Health Hospital. Figure 1. Generation of the experimental animals. Representative graphics for the characterization of the animal models. CD-1 mice fed for 12 months with standard food ad libitum first stage were separated into animals fed standard food ad libitum and animals fed an HCD ad libitum for a period of 17 weeks second stage. Some animals were subjected to CR for a period of 13 weeks before sacrifice third stage. The experimental groups included mice fed a 3. The mice initially fed 3. The animals fed the 5. The daily amount of food of the CR-treated animals was periodically adjusted according to changes in body weight to maintain nutritional balance relative to the body mass index BMI. The transition from the standard food or HCD ad libitum to CR was gradually achieved over a period of one week. The mice were monitored daily by laboratory members and animal health technicians. Before the experimental endpoint, the mice experienced minimal pain and stress during routine handling, body weight determination, echocardiography procedures, and blood collection from the tail vein to measure blood glucose levels. No ill or deceased mice were observed before the experimental endpoint when the mice were 19 to 20 months old. The animals were euthanized by the cervical dislocation technique. Cardiac function and geometry were evaluated in anesthetized 1. The transmission frequency was set at 30 MHz, the acquisition gain was The animals were placed on a homeothermic table, and the core temperature was maintained at 37°C. The heart rates in the experimental groups were consistently monitored between ~ and ~ bpm. The interventricular septal thickness at diastole IVS-d , interventricular septal thickness at systole IVS-s , LV internal end-diastolic diameter LVIDD , LV internal end-systolic diameter LVIDs , LV posterior wall dimension-diastole LVPW-d , and LV posterior wall dimension-systole LVPW-s were measured. Vevo LAB 3. All measures derived from echocardiography were obtained by averaging the readings of three consecutive and complete cardiac cycles. WHT was collected and weighed after completely removing the blood with ice-cold PBS. Samples were immediately analyzed or flash-frozen in liquid nitrogen and stored until execution of the experiments. The samples were heated on a boiling electric plate for 1 hour and were rotated and shaken once every 10 min. Fifteen milliliters of hot water was added and mixed well, and the mixture was filtered. The precipitate was washed with hot water, and after neutralization, dried in an oven at °C ± 5°C for 1 hour and then allowed to cool. according to the instructions provided by the manufacturer. Briefly, mg of tissue was homogenized on ice with 1 ml of Reagent I and 10 μL of Reagent III. The homogenate was centrifuged at × g for 5 min 4°C , and the supernatant was transferred into a new centrifuge tube and centrifuged at 11, × g for 10 min at 4°C. The pellet, which contained the mitochondrial extract, was mixed with μL of Reagent II and 2 μL of Reagent III. Then, the samples were resuspended and used to detect the activity of mitochondrial respiratory chain complexes with a Multiskan GO microplate reader Thermo Fisher Scientific, Oy Ratastie 2, P. Box FI, Finland. For complex I, 10 μL of the sample, 15 μL of Working Reagent VI, and μL of Working Solution were mixed and poured into a well UV microplate. The absorbance was immediately read at nm A 1 and after 2 min A 2. For complex III, 10 μL of the sample, 25 μL of Reagent VI, and μL of working solution were mixed and poured into a well microplate. For complex IV, 10 μL of sample and μL of working solution were mixed and poured into a well microplate. mtCK, a sarcomeric isoenzyme, was analyzed in the WHT with the Mouse CKMT2 ELISA Kit Quanzhou Ruixin Biological Technology Co. according to the instruction manual. Briefly, 50 μL of standard or sample was added to each appropriate well all standards and samples were added in triplicate. One hundred microliters of enzyme conjugate was added to each standard or sample well except for the blank wells. The plate was covered with an adhesive strip and incubated for 60 min at 37°C. Then, the plate was washed four times. After the washing procedure, all wells were aspirated, and the plate was rewashed four times using Wash Buffer 1X. After the final wash, the plate was inverted and dried by tapping the plate on absorbent paper until no moisture was evident. Substrate A 50 μL and Substrate B 50 μL were added to each well and gently mixed, and the plate was incubated for 15 min at 37°C in the absence of light. Then, 50 μL of stop solution was added to each well. Finally, the optical density OD was read at nm using a microtiter plate reader within 15 min. DNA was isolated from WHT of the 3. through comparison of mtDNA and nuclear n DNA measured by quantitative real-time polymerase chain reaction qPCR. Tissues preserved in liquid nitrogen were homogenized, and the RNA was extracted with Takara RNAiso PLUS Total RNA Extraction Reagent Takara Bio, Inc. DNA was extracted with a TIANamp Genomic DNA Kit TIANGEN. The total nucleic acid concentration and OD were assayed by UV spectrophotometry. cDNA was obtained with a Takara kit RRQ. qPCR was performed with ng of target DNA. Tissues were homogenized with 5 volumes of radioimmunoprecipitation assay RIPA buffer Solarbio ® Life Sciences , and the supernatants were fractionated by SDS—PAGE. One hundred milligrams of WHT homogenate from the 3. Homogenates were analyzed with a TRAPeze RT Telomerase Detection Kit Millipore for fluorometric detection and real-time quantification of telomerase activity. Briefly, 50 to mg of frozen WHT was homogenized and resuspended in μl of CHAPS lysis buffer. Samples were incubated on ice for 30 min and centrifuged at 12, × g for 20 min 4°C. Correlations were tested by Pearson analysis, and the data were processed using GraphPad Prism 8. Western blot analysis and protein densitometry were conducted with Image Lab 5. A P value The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board of Chengdu Jinjiang Hospital for Maternal and Child Health Care. Mice were daily monitored by laboratory members and by animal health technicians. At the end of the second stage of animal model development, mice fed the HCD ad libitum in the high-calorie groups, HCGs showed significant increases in body weight Figure 2A. Interestingly, the HCG mice presented lower daily volumes of ingested food Figure 2B than the mice fed the standard 3. Nevertheless, due to the food composition, the caloric intake of the HCGs was considerably higher than that of their control counterparts Figure 2C. Figure 2. Physiological changes during and after the development of the experimental animal model. The graphics are representations of 1 of the 3 cohorts of animals. Average body weights of the animal groups before CR A. Average food ingestion of the animal groups before CR, expressed in grams B. Average caloric intake of the animal groups before CR C. Animal weights during the CR period, expressed in grams D. The mRNA and protein levels of Fabp4 were used to predict INTM and IM fat infiltration E. Negative values represent downregulation. The protein expression of Fabp4 was obtained by Western blot analysis and quantified with Image Lab 6. The values were normalized to GAPDH expression; the 3. Total fat content in the WHT, as determined by acid hydrolysis F. Comparison of the blood glucose levels of mice during weeks 9 to 13 of dietary restriction G. The data are the mean ± SD. Although the groups with different feeding regimens 3. The mRNA and protein expression of the adipose-type cytoplasmic fatty acid-binding protein Fabp4 Figure 2E was used in this work to predict intermyocellular INTM and intramyocellular IM fat infiltration [ 50 ]. The transcriptional and translational data suggested higher amounts of INTM and IM lipid content in the 5. Moreover, the 3. Due to the small sizes of mice, it is impossible to distinguish INTM and IM adiposity; thus, all available studies on IM adipogenesis in mice refer to both INTM and IM fat [ 51 ]. Moreover, due to the intricate and nonhomogeneous structure of the heart, we analyzed the total lipid content in the heart by the acid hydrolysis technique Figure 2F. Since this assay requires the use of whole organ tissue, a separate cohort of 8 animals per group was selected according to the experimental animal model standards. WHT was collected and then hydrolyzed with hydrophobic acid, as explained in the Materials and Methods section 2. The results showed a significant increase in the total lipid content in the 5. In addition to the other variables described above, we included glucose levels in our characterization of the experimental animal model Figure 2G. As expected, mice subjected to CR showed better blood glucose levels than ad libitum -fed mice, while the 5. The role of CRMs in CVDs. Perspectives and conclusions. Journal Article Editor's Choice. Caloric restriction mimetics for the treatment of cardiovascular diseases. Sebastiano Sciarretta , Sebastiano Sciarretta. Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome. Corresponding authors. maiuri crc. sciarretta uniroma1. Oxford Academic. Google Scholar. Maurizio Forte. Department of AngioCardioNeurology, IRCCS Neuromed. Francesca Castoldi. Cell Biology and Metabolomics platforms, Gustave Roussy Cancer Campus. Giacomo Frati. Francesco Versaci. Division of Cardiology, S. Maria Goretti Hospital. Junichi Sadoshima. Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School. Guido Kroemer. Suzhou Institute for Systems Medicine, Chinese Academy of Sciences. Department of Women's and Children's Health, Karolinska Institute, Karolinska University Hospital. Maria Chiara Maiuri. Editorial decision:. PDF Split View Views. Select Format Select format. ris Mendeley, Papers, Zotero. enw EndNote. bibtex BibTex. Article CAS PubMed Google Scholar. Stanek A, Fazeli B, Bartuś S, Sutkowska E. 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| Cutting about calories a day might benefit your heart, study finds | CNN | Epigallocatechingallate EGCG promotes autophagy-dependent survival via influencing the balance of mTOR-AMPK pathways upon endoplasmic reticulum stress. The slices were then immersed in TTC phosphate buffer solution for 5 min at 37 °C. Louis S, Tappu RM, Damms-Machado A, Huson DH, Bischoff SC. Alfaras I, Di Germanio C, Bernier M, Csiszar A, Ungvari Z, Lakatta EG, et al. The protective effect of quercetin on CVD has been demonstrated in human studies [ 49 , , , ]. |
| Targeting Cardiovascular Risk Factors Through Dietary Adaptations and Caloric Restriction Mimetics | Martin Maldonado: Faloric, Experiments, Data Enhanced recovery nutrition, Investigation, Methodology, Visualization, Writing rsstriction review caloric restriction and heart health Strategic fat burning. Recent Findings Calorie restriction may be Hydrating Drink Choices approach to reduce the development of atherosclerosis. Yan, X. Sorry, a shareable link is not currently available for this article. Perspectives and conclusions. db PubMed Abstract CrossRef Full Text Google Scholar. Aging and cardiovascular disease: lessons from calorie restriction. |
Caloric restriction and heart health -
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Calorie restriction and aging in humans. Annu Rev Nutr. Download references. Department of Applied Health Science, Indiana University School of Public Health, E. Pennington Biomedical Center, Perkins Rd, Baton Rouge, LA, USA. You can also search for this author in PubMed Google Scholar. Correspondence to Cydne A.
Cydne A. Kishore M. Gadde reports grants to his institution from AstraZeneca, BioKier, and National Institutes of Health, outside the submitted work. This article is a review of recent published work in the field of calorie restriction and cardiovascular disease.
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Provided by the Springer Nature SharedIt content-sharing initiative. Abstract Purpose of Review Calorie restriction CR has emerged as a non-pharmacological treatment to prevent cardiovascular disease CVD. Recent Findings Calorie restriction may be an approach to reduce the development of atherosclerosis.
Summary The evidence for CR in CVD prevention has accumulated in the recent years. Access this article Log in via an institution. Article PubMed Google Scholar Agency for Healthcare Research and Quality. html Man AWC, Li H, Xia N. Article Google Scholar Daiber A, Steven S, Weber A, Shuvaev VV, Muzykantov VR, Laher I, Li H, Lamas S, Münzel T.
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Furthermore, metformin increases the expression and activity of SIRT1, while it attenuates the activation of PGC1α, a central energy metabolism regulator As most of the research endeavors focused on the glucose-lowering effect of metformin, it is not surprising that the majority of clinical trials were designed to investigate the beneficial role of metformin on diabetes mellitus type 2.
However, several human studies assessed the impact of metformin monotherapy on other age-associated comorbidities as well. For example, metformin reduces pro-inflammatory cytokine levels in older diabetic patients, suggesting that metformin has the potential to attenuate age-related low-grade chronic inflammation, reduce the predisposition toward inflammation-related comorbidities, and improve survival of diabetic patients In another clinical investigation, the use of metformin was assessed in the context of cardiovascular outcome in patients with diabetes mellitus type 2 and chronic kidney disease The authors that analyzed data from the TREAT trial demonstrated that metformin reduces the incidence of cardiovascular events as well as cardiovascular death and all-cause mortality.
Importantly, metformin was found to be safe for patients with chronic kidney disease, which is in contrast with the previous assertion that metformin commonly induces lactic acidosis In pubertal children with diabetes mellitus type 2 and metabolic syndrome, metformin improves various health parameters, including BMI, leptin levels, fat mass and liver fat Interestingly, some of these beneficial effects were maintained after completing the 24 months of metformin treatment, suggesting that metformin is well-tolerated and has a potential long-term benefit in adolescents at risk.
In the REMOVAL trial, patients with diabetes mellitus type 1 displayed lower LDL-cholesterol levels after 3 years of metformin treatment Recently, a meta-analysis that included 16 studies and nearly 2 million participants revealed that metformin reduces overall cardiovascular risk, including mortality and incidence, in patients with diabetes mellitus type 2 Another comprehensive meta-analysis of studies described a general drop in all-cause mortality and occurrence of cardiovascular disease in diabetic patients upon metformin treatment as compared to diabetic patients receiving other medication and, interestingly, even non-diabetic subjects These observations highlight that metformin could extend lifespan and healthspan by acting as a geroprotective drug.
However, studies in healthy or non-diabetic populations are rare and showed conflicting results. For example, the CAMERA study failed to produce the beneficial effects of metformin on cardiovascular disease prevention in non-diabetic patients with high cardiovascular risk By contrast, 6 weeks of metformin treatment reduced body weight, improved insulin secretion, lowered LDL and triglyceride levels in an elderly population exhibiting impaired glucose tolerance but no previous history of diabetes Of note, the 6-year Targeting Aging with MEtformin TAME clinical trial 3 , which started in as a large randomized controlled and multicenter study, including over 3, participants between the ages of 65—79 without diabetes but who are at high risk for the development of chronic diseases of aging, is expected to generate highly valuable new knowledge about the impact of metformin on the primary outcome of death and major age-related chronic disease development, such as cardiovascular disease, cancer, and dementia Recent years have seen a growing interest in understanding how dietary interventions shape and interact with the most common cardiovascular risk factors, including hypertension, obesity, metabolic syndrome, and diabetes mellitus type 2.
Substantial cardiometabolic improvements have been reported with fasting interventions such as reduction in blood pressure, body weight and fat mass, lower blood glucose, and improvement in insulin sensitivity, both in experimental and clinical studies.
Although caloric restriction consistently improves several aspects of health, its application has been hampered by poor compliance and adverse side effects on bone health and immune response, especially in the elderly. To overcome these major hurdles, clinical trials on alternate-day or intermittent fasting, with higher statistical power and follow-up, are strongly needed before they can be implemented as a treatment strategy.
Individuals practicing alternate-day or intermittent fasting should consider to include regular physical activity to maintain their energy expenditure. Emerging evidence indicates that the optimal cardioprotective diet is constructed around the traditional Mediterranean eating pattern.
Another interesting aspect that warrants further attention is the effect of caloric restriction mimetics or dietary interventions aimed at weight loss on the gut microbiome changes in obese patients with diabetes mellitus type 2 or metabolic syndrome. Although these interventions propose beneficial clinical outcomes, their effect on the gut microbiome is only beginning to unfold.
Interestingly, a combination therapy of resveratrol and spermidine synergistically induces autophagy at doses, which do not trigger effects of the same magnitude if administered alone.
At present, however, it remains elusive what is the optimal dose for any of the caloric restriction mimetics that could provide health benefits or protect humans at risk of cardiovascular disease.
Unlike the current drug development approaches that focus on individual diseases in isolation and consider specificity as a desirable outcome in disease prevention and treatment, both caloric restriction mimetics and caloric restriction exhibit a spurious mode of action, intercepting with multiple different targets Such pleiotropic mode of action appears advantageous in targeting the complex process of aging as the greatest risk factor for cardiovascular diseases and associated comorbid conditions.
Thus, dietary interventions should aim to maintain optimum health and prevent cardiovascular diseases by attenuating the molecular causes of biological aging directly. Non-cell autonomous effects of caloric restriction mimetics and caloric restriction itself, such as the anti-inflammatory or immune modulatory functions, are increasingly viewed as relevant as cell autonomous mechanisms.
Taking this into account, more research is needed to ascertain how different forms of fasting and caloric restriction mimetics can be the most favorable to further improve cardiometabolic markers in healthy adults and patients living with or at risk of developing cardiovascular disease.
Based on the currently available data, harnessing caloric restriction mimetics or dietary interventions, such as intermittent fasting or the Mediterranean diet represent a promising preventive venue, which might reduce cardiovascular risk and the burden of cardiovascular disease.
SS conceptualized the manuscript. JV, MA, and SS contributed to the research for writing the manuscript. JV and SL-H designed the figures and table. All authors contributed to the discussion, writing, and review of the manuscript.
This work was supported by the Austrian Science Fund—FWF I and the European Research Area Network on Cardiovascular disease ERA-CVD, MINOTAUR to SS.
MA acknowledges funding received from the European Society of Cardiology, the Austrian Society of Cardiology Präsidentenstipendium der ÖKG , and the Medical University of Graz START Fund.
SL-H reports funding by the Austrian Science Fund - FWF V and BioTechMed-Graz Young Researcher Groups [YRG]. MA and SS are involved in a patent application related to the cardiometabolic effects of caloric restriction mimetics.
The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.
Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. JV is currently trained as a PhD candidate in the Program Molecular Medicine at the Medical University of Graz.
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Military Medical Research volume 9 caloriv, Caloric restriction and heart health number: 33 Cardio exercises for muscle definition this article. Enhanced recovery nutrition details. The literature is full of claims anv the consumption of polyphenol or polyamine-rich foods that offer some protection from developing cardiovascular disease CVD. This is achieved by preventing cardiac hypertrophy and protecting blood vessels through improving the function of endothelium. However, do these interventions work in the aged human hearts?
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