Nucleotide Content Research Articles

Human cytomegalovirus overcomes SAMHD1 restriction in macrophages via pUL97.

The host restriction factor sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) is an important component of the innate immune system. By regulating the intracellular nucleotide pool, SAMHD1 influences cell division and restricts the replication of viruses that depend on high nucleotide concentrations. Human cytomegalovirus (HCMV) is a pathogenic virus with a tropism for non-dividing myeloid cells, in which SAMHD1 is catalytically active. Here we investigate how HCMV achieves efficient propagation in these cells despite the SAMHD1-mediated dNTP depletion. Our analysis reveals that SAMHD1 has the capability to suppress HCMV replication. However, HCMV has evolved potent countermeasures to circumvent this block. HCMV interferes with SAMHD1 steady-state expression and actively induces SAMHD1 phosphorylation using the viral kinase pUL97 and by hijacking cellular kinases. These actions convert SAMHD1 to its inactive phosphorylated form. This mechanism of SAMHD1 inactivation by phosphorylation might also be used by other viruses to overcome intrinsic immunity.

Anti-Microbiological, Anti-Hyperglycemic and Anti-Obesity Potency of Natural Antioxidants in Fruit Fractions of Saskatoon Berry.

The aim of the present work was to evaluate for content of phytochemicals (monophosphate nucleotides, free amino acids, polyphenols), and for anti-microbiological, anti-diabetic (ability to inhibit pancreatic lipase, α-glucosidase, and α-amylase), and antioxidant activities in seven selected fruit and fruit fractions of Amelanchier alnifolia. Most of the fruit and fruit fractions analyzed in this study have not been examined in this respect until now. The content of monophosphate nucleotides and free amino acids were tested by ultra-performance liquid chromatography coupled with photodiode array detector and electrospray ionization-mass spectrometry (UPLC-PDA-ESI-MS). The distribution of the examined compounds and biological activity differed significantly depending on the tested fruit and parts of the fruit. Cultivars “Smoky” and “Thiessen” had a high content of essential free amino acids, monophosphate nucleotides, and the highest antioxidant activity. They were also accountable for the high ability to inhibit Enterococcus hirae (anti-bacterial activity), of activity toward α-amylase, α-glucosidase, and pancreatic lipase. Moreover, the fruit peel was abundant in polyphenolic compounds and showed the highest antioxidative activity, which were strongly correlated with each other. In addition, the peel was characterized by a high concentration of monophosphate nucleotides, free amino acids, and were responsible above all for the strong ability to inhibit pancreatic lipase enzymes contributing to the development of obesity. The seeds were rich in uridine 5’-monophosphate, and total essential and non-essential free amino acids, whose contents correlated with the inhibitory activity toward α-amylase and α-glucosidase. The fruit flesh showed a high content of total free amino acids (hydroxy-L-proline, O-phosphoethanolamine, L-citruline). There was a positive correlation between antioxidant capacity and the content of polyphenolic compounds, nucleotide, and ability to inhibit pancreatic lipase, and between anti-hyperglycemic and free amino acids in fruits and fruit fractions. Therefore, the tested fruit of A. alnifolia and their fractions could be essential ingredients of new functional products and/or probiotic food.

Inosine pranobex enhances human NK cell cytotoxicity by inducing metabolic activation and NKG2D ligand expression.

Inosine pranobex (IP) is a synthetic immunomodulating compound, indicated for use in the treatment of human papillomavirus‐associated warts and subacute sclerosing panencephalitis. Previous studies demonstrate that the immunomodulatory activity of IP is characterized by enhanced lymphocyte proliferation, cytokine production, and NK cell cytotoxicity. The activation of NKG2D signaling on NK cells, CD8+ T cells, and γδ T cells also produces these outcomes. We hypothesized that IP alters cellular immunity through the induction of NKG2D ligand expression on target cells, thereby enhancing immune cell activation through the NKG2D receptor. We tested this hypothesis and show that exposure of target cells to IP leads to increased expression of multiple NKG2D ligands. Using both targeted metabolic interventions and unbiased metabolomic studies, we found that IP causes an increase in intracellular concentration of purine nucleotides and tricarboxylic acid (TCA) cycle intermediates and NKG2D ligand induction. The degree of NKG2D ligand induction was functionally significant, leading to increased NKG2D‐dependent target cell immunogenicity. These findings demonstrate that the immunomodulatory properties of IP are due to metabolic activation with NKG2D ligand induction.

EpiSAFARI: sensitive detection of valleys in epigenetic signals for enhancing annotations of functional elements.

MotivationFunctional genomics experiments generate genomewide signal profiles that are dense information sources for annotating the regulatory elements. These profiles measure epigenetic activity at the nucleotide resolution and they exhibit distinctive patterns as they fluctuate along the genome. Most notable of these patterns are the valley patterns that are prevalently observed in assays such as ChIP Sequencing and bisulfite sequencing. The genomic positions of valleys pinpoint locations of cis-regulatory elements such as enhancers and insulators. Systematic identification of the valleys provides novel information for delineating the annotation of regulatory elements. Nevertheless, the valleys are not reported by majority of the analysis pipelines.ResultsWe describe EpiSAFARI, a computational method for sensitive detection of valleys from diverse types of epigenetic profiles. EpiSAFARI employs a novel smoothing method for decreasing noise in signal profiles and accounts for technical factors such as sparse signals, mappability and nucleotide content. In performance comparisons, EpiSAFARI performs favorably in terms of accuracy. The histone modification valleys detected by EpiSAFARI exhibit high conservation, transcription factor binding and they are enriched in nascent transcription. In addition, the large clusters of histone valleys are found to be enriched at the promoters of the developmentally associated genes. Differential histone valleys exhibit concordance with differential DNase signal at cell line specific valleys. DNA methylation valleys exhibit elevated conservation and high transcription factor binding. Specifically, we observed enriched binding of transcription factors associated with chromatin structure around methyl-valleys.Availability and implementationEpiSAFARI is publicly available at https://github.com/harmancilab/EpiSAFARI.Supplementary information Supplementary data are available at Bioinformatics online.

Effects of three types of bone marrow extracts treated with different treatment methods on the taste of chicken soup.

Bone marrow extracts (BME) are good flavor enhancing substance. Three types of BME (from porcine, chicken and bovine) were treated by enzymatic hydrolysis or Maillard reaction. To explore their effects on soup taste, they were added into chicken and non-chicken soups. The contents of free amino acids, nucleotides, peptides and soluble solids in the soup were measured and the taste activity value and equivalent umami concentration value were calculated, in addition to sensory evaluation. These parameters were weighted according to a certain ratio. Most taste-active substances increased upon enzymatic hydrolysis, while reached their maximum values after Maillard reaction. In addition, the presence of chicken alleviated bitter and fatty tastes in soups added with bone extracts, thus causing the soup to be more flavorful. Sensory evaluation results revealed that umami and kokumi tastes of soups supplemented with Maillard reaction-treated bone marrow extracts were more intense.

An ensemble of cryo-EM structures of TRiC reveal its conformational landscape and subunit specificity

TRiC/CCT assists the folding of ∼10% of cytosolic proteins through an ATP-driven conformational cycle and is essential in maintaining protein homeostasis. Here, we determined an ensemble of cryo-electron microscopy (cryo-EM) structures of yeast TRiC at various nucleotide concentrations, with 4 open-state maps resolved at near-atomic resolutions, and a closed-state map at atomic resolution, revealing an extra layer of an unforeseen N-terminal allosteric network. We found that, during TRiC ring closure, the CCT7 subunit moves first, responding to nucleotide binding; CCT4 is the last to bind ATP, serving as an ATP sensor; and CCT8 remains ADP-bound and is hardly involved in the ATPase-cycle in our experimental conditions; overall, yeast TRiC consumes nucleotide in a 2-ring positively coordinated manner. Our results depict a thorough picture of the TRiC conformational landscape and its allosteric transitions from the open to closed states in more structural detail and offer insights into TRiC subunit specificity in ATP consumption and ring closure, and potentially in substrate processing.

Characterization of Withania somnifera chloroplast genome and its comparison with other selected species of Solanaceae

Withania somnifera (L) Dunal, a wonder herb of family Solanaceae, has multiple medicinal properties. Here, we reported the chloroplast genome sequence of Withania somnifera (154,386 bp) which comprises of a large single copy region (85,688 bp), and a small single copy region (18,464 bp), separated by a pair of large inverted repeats (25,117 bp). The chloroplast genome has 132 genes including 86 protein-coding, 37 tRNAs and 8 rRNAs. Comparison of chloroplast genomes of Withania somnifera with four other Solanaceae species revealed similarities in genomic features, including structure, nucleotide content, codon usage, RNA editing sites, simple sequence repeats (SSRs), oligonucleotide repeats, and tandem repeats. We identified 147 simple sequence repeats in protein-coding, and 229 in non-protein-coding regions. We observed numerous post-transcriptional substitutions of Serine to Leucine, specifically at the second nucleotide position of the codon. Maximum likelihood and maximum parsimony tree reconstructed displayed Withania somnifera a sister taxon of Physalis peruviana.

Short-Term Oral UMP/UR Administration Regulates Lipid Metabolism in Early-Weaned Piglets.

Simple SummaryUridine monophosphate (UMP) and uridine (UR) are rich in sow’s milk. The results from this study showed that UMP and UR affect the lipid profile and lipid metabolism in weanling piglets. It is suggested that UMP and UR improve the energy status in early-weaned piglets.As a main ingredient of milk, the nucleotides content is about 12–58 mg/g, which plays a critical role in maintaining cellular function and lipid metabolism. This study was conducted to evaluate the effects of short-term uridine monophosphate (UMP) and uridine (UR) administration on lipid metabolism in early-weaned piglets. Twenty-one weaned piglets (7 d of age; 3.32 ± 0.20 kg average body weight) were randomly assigned into three groups: The control (CON), UMP, and UR group, and oral administered UMP or UR for 10 days, respectively. The results showed that supplementation with UMP significantly increased (p < 0.05) serum low density lipoprotein (LDL) and tended to increase (p = 0.062) serum total cholesterol (TC) content of piglets when compared with the other two groups. Oral administration with UMP and UR significantly decreased (p < 0.05) the serum total bile acid (TBA) and plasma free fatty acids (FFA) of piglets, and significantly reduced the fatty acid content of C12:0 (p < 0.01) and C14:0 (p < 0.05) in liver. Experiments about key enzymes that are involved in de novo synthesis of fatty acid showed that the gene expression of liver X receptors (LXRα), sterol regulatory element-binding transcription factor 1 (SREBP1c), fatty acid desaturase 2 (FADS2), and fatty acid elongase 5 (ELOVL5) were remarkably down-regulated (p < 0.05) with UMP and UR treatment, and key factors of adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), and carnitine palmitoyl transferase 1 (CPT-1α) involved in fatty acid catabolism were also decreased (p < 0.05). Additionally, the protein expression of phosphorylated-mTOR was not affected while phosphorylation of AKT was repressed (p < 0.05). In conclusion, short-term oral UMP or UR administration could regulate fatty acid composition and lipid metabolism, thus providing energy for early-weaned piglets.

Extracellular Nucleotides and P2 Receptors in Renal Function.

The understanding of the nucleotide/P2 receptor system in the regulation of renal hemodynamics and transport function has grown exponentially over the last 20 yr. This review attempts to integrate the available data while also identifying areas of missing information. First, the determinants of nucleotide concentrations in the interstitial and tubular fluids of the kidney are described, including mechanisms of cellular release of nucleotides and their extracellular breakdown. Then the renal cell membrane expression of P2X and P2Y receptors is discussed in the context of their effects on renal vascular and tubular functions. Attention is paid to effects on the cortical vasculature and intraglomerular structures, autoregulation of renal blood flow, tubuloglomerular feedback, and the control of medullary blood flow. The role of the nucleotide/P2 receptor system in the autocrine/paracrine regulation of sodium and fluid transport in the tubular and collecting duct system is outlined together with its role in integrative sodium and fluid homeostasis and blood pressure control. The final section summarizes the rapidly growing evidence indicating a prominent role of the extracellular nucleotide/P2 receptor system in the pathophysiology of the kidney and aims to identify potential therapeutic opportunities, including hypertension, lithium-induced nephropathy, polycystic kidney disease, and kidney inflammation. We are only beginning to unravel the distinct physiological and pathophysiological influences of the extracellular nucleotide/P2 receptor system and the associated therapeutic perspectives.

Identification of optimal fluorescent probes for G-quadruplex nucleic acids through systematic exploration of mono- and distyryl dye libraries.

A library of 52 distyryl and 9 mono-styryl cationic dyes was synthesized and investigated with respect to their optical properties, propensity to aggregation in aqueous medium, and capacity to serve as fluorescence “light-up” probes for G-quadruplex (G4) DNA and RNA structures. Among the 61 compounds, 57 dyes showed preferential enhancement of fluorescence intensity in the presence of one or another G4-DNA or RNA structure, while no dye displayed preferential response to double-stranded DNA or single-stranded RNA analytes employed at equivalent nucleotide concentration. Thus, preferential fluorimetric response towards G4 structures appears to be a common feature of mono- and distyryl dyes, including long-known mono-styryl dyes used as mitochondrial probes or protein stains. However, the magnitude of the G4-induced “light-up” effect varies drastically, as a function of both the molecular structure of the dyes and the nature or topology of G4 analytes. Although our results do not allow to formulate comprehensive structure–properties relationships, we identified several structural motifs, such as indole- or pyrrole-substituted distyryl dyes, as well as simple mono-stryryl dyes such as DASPMI [2-(4-(dimethylamino)styryl)-1-methylpyridinium iodide] or its 4-isomer, as optimal fluorescent light-up probes characterized by high fluorimetric response (I/I0 of up to 550-fold), excellent selectivity with respect to double-stranded DNA or single-stranded RNA controls, high quantum yield in the presence of G4 analytes (up to 0.32), large Stokes shift (up to 150 nm) and, in certain cases, structural selectivity with respect to one or another G4 folding topology. These dyes can be considered as promising G4-responsive sensors for in vitro or imaging applications. As a possible application, we implemented a simple two-dye fluorimetric assay allowing rapid topological classification of G4-DNA structures.

Prospects for the Use of Thermal Extracts of Brucella abortusI-206 in S-and L-Forms in the Diagnosis and Prevention of Brucellosis

Currently, one of the topical areas of research is the development of new antigen preparations for the specific diagnosis and prevention of brucellosis, since indication of the pathogen and prevention of the disease is complicated by the ability of brucella to dissociate, and live vaccines used for specific prevention of brucellosis have residual virulence. Thermal extracts (TE) obtained from Brucella abortus I-206 in the L- and S-form can be used as such promising antigens. It is known that TE in the L- and S-forms have immunogenic properties, as well as a modulating effect on the proliferation of immunocompetent cells, morphological changes in the immunocompetent organs of experimental animals.The aimof the work is to study the effect of Brucella abortus thermal extracts in L- and S-forms on the functional state of the cells of experimental animals.Materials and methods. The study was performed on 100 certified white mice. As objects of study, we used the B. abortus I-206 TE in L- and S-forms. Evaluation of the effect of antigenic drugs on the functional state of phagocytes of laboratory animals in vitro was performed on peritoneal macrophages. The total activity of the respiratory chain enzymes in the NBT-test and superoxide dismutase was determined. Cells of intact animals served as controls. As a positive control, a commercial antigenic LPS preparation Escherichia coli was used. The content of cyclic nucleotides in homogenates of immunocompetent organs was determined using ELISA.Results.This study presents materials on the study of the effect of TE on the bactericidal activity of phagocytes and the level of cyclic nucleotides in immunocompetent organs. It has been established that TEs activate oxygen-dependent bactericidal systems of phagocytes. When studying the effect of TE on the content of cyclic nucleotides in immunocompetent organs of white mice, an increase in their concentration was revealed, indicating an increase in the functional activity of the cells.Conclusion.The obtained data make it possible to substantiate the need for a further detailed study of the immunogenic properties of B. abortus TE in the L- or S-form on the organism of experimental animals.

Redox balance and tissue development of juvenile Piaractus mesopotamicus subjected to high stocking density and fed dry diets containing nutraceutical food

Colostrum is a source of molecules with nutraceutical features that can attenuate the consequences of adverse conditions, such as densification. Thus, the redox balance and tissue development of juvenile Piaractus mesopotamicus subjected to high stocking density and fed diets containing lyophilized bovine colostrum (LBC) were evaluated. Juveniles were distributed into 16 cages making 50 kg fish m -3 and fed diets containing 0, 10, 20 and 30% inclusion of LBC (n = 4). After 30 days, enteric, hepatic, muscular, renal and branchial tissue were sampled for the determination of glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase activity, oxygen radical absorbance capacity (ORAC), lipid peroxidation and protein and nucleotides content. SOD activity and DNA content were higher in 20% LBC compared to the others in the enteric tissue ( P < 0.10). ORAC value in erythrocytes was higher in 30% LBC than 0 and 10% LBC ( P < 0.10). Juveniles fed 10% LBC showed higher lipid peroxidation in liver than 0 and 20% LBC ( P < 0.10) and those fed 20% LBC showed lower protein/RNA ratio compared to the others ( P < 0.10). Bovine colostrum determined a decrease in liver protein synthesis and increased in intestinal DNA content with an intake of 20% of this milk secretion. Additionally, LBC increased the protection of the enteric tissue of juveniles from superoxide radicals and blood antioxidant capacity. We conclude that bovine colostrum can be used as a nutraceutical food for fish, with positive effect in redox balance and tissue development in high concentrations of inclusion in the diet, 20 and 30%.

Complete mitochondrial genome and the phylogenetic position of the stellate puffer (Arothron stellatus)

The complete mitochondrial genome of the stellate puffer (Arothron stellatus) was first determined in this study. It was a 16,475 bp circular molecule and consisted of 37 genes with typical gene order in vertebrate mitogenome. Its nucleotide content was 29.0% A, 32.0% C, 15.9% G and 23.1% T. This mitogenome had 30 bp short intergenic spaces located in 12 gene junctions and 28 bp overlaps located in 7 gene junctions. In the protein-coding genes, two start codons (GTG and ATG) and two stop codons (TAG and TAA/TA/T) were found. The 22 tRNA genes ranged from 64 bp (tRNA-Cys) to 74 bp (tRNA-Leu1 and tRNA-Lys). The phylogenetic result showed that Takifugu xanthopterus was most closely related to the reef-related A. stellatus among all Tetraodontiformes species.

The chloroplast genome of an important herb species, Ephedra sinica (Ephedraceae)

Ephedra sinica has been utilized by humans for over 5000 years as Chinese herbal medicine in China. In this study, we reported the complete chloroplast genome of E. sinica. The chloroplast genome of E. sinica is 109,550 bp in length as the circular, which harbors a large single-copy (LSC) region of 59,962 bp, a small single-copy (SSC) region of 8106 bp and separated by a pair of inverted-repeat (IR) regions of 20,742 bp each. The overall nucleotide content of the chloroplast genome: A of 31.2%, T of 32.1%, C of 18.4% G of 18.3%, and 36.7% GC content. This chloroplast genome contains 118 genes, which includes 74 protein-coding genes (PCGs), 36 transfer RNA (tRNAs) and 8 ribosome RNA (rRNAs). Phylogenetic analysis result showed that E. sinica was most closely related to Ephedra equisetina in the family Ephedraceae using the Neighbor-Joining (NJ) method.

The complete mitochondrial genome sequences of five Otophysi species (Vertebrata, Teleostei)

Complete mitochondrial genomes of the characiform fishes Astyanax fasciatus, Astyanax altiparanae, Hoplias malabaricus (Karyomorph A) and the Gymnotiformes species Gymnotus sylvius and Gymnotus cuia were characterized in the present study. The whole mitogenomes varied from 16,400bp (A. fasciatus) to 17,730 bp (A. altiparanae) long and all of them consisted of 13 protein-coding genes, 22 tRNAs, 2 rRNAs genes, a control region, and origin of light-strand replication. The gene order was similar among all the analyzed species. The nucleotide content of all mitogenomes was also similar, with 29.58–30.95% for A, 27.02–28.65% for T, 26.29–29.99% for C, and 14.41–15.67% for G.

Characterization of the complete chloroplast genome of Bletilla striata (Orchidaceae: Bletilla), the herb in China

Chloroplast (cp) genome sequences have been become a useful tool for phylogenetic and evolutionary studies in the herb. In this study, the complete cp genome of Bletilla striata was assembled. The complete cp genome is circular of 157,016 base pairs (bp) in length, which harbours a large single-copy region (85,821 bp), a small single-copy region (17,743 bp), and two inverted-repeat regions (each one of 26,726 bp). The cp genome of B. striata contains 139 genes, including 94 protein-coding genes (PCGs), 37 transfer RNA (tRNAs), and 8 ribosome RNA (rRNAs). The overall nucleotide content of the cp genome is A of 31.0%, T of 31.8%, C of 18.9%, and G of 18.3%, with a total AT content of 62.8% and GC content of 37.2%. However, the phylogenetic relationship analysis using maximum-likelihood (ML) method, which the result showed that the position of B. striata was situated as Bletilla ochracea in Orchidaceae. This study will be helpful for studies on the cp genetic engineering and medicinal herb value of Orchidaceae species in further.

Characterization of the complete chloroplast genome of a common Chinese medicinal herb, Eriocaulon buergerianum (Eriocaulaceae: Eriocaulon)

Eriocaulon buergerianum is a common Chinese medicinal herb and belongs to the family Eriocaulaceae genus Eriocaulon the annual herbs. In this study, the complete chloroplast genome of E. buergerianum was assembled and reported. The complete chloroplast genome of E. buergerianum is 157,016 bp in length as the circular, which harbours a large single-copy region (LSC) of 81,534 bp, a small single-copy region (SSC) of 17,114 bp, and two inverted-repeat regions (IRs) of 26,393 bp each one. The overall nucleotide content of the chloroplast genome: A of 31.8%, T of 32.4%, C of 18.2% G of 17.6%, and 35.8% GC content. The chloroplast genome of E. buergerianum contains 133 genes, which includes 88 protein-coding genes (PCGs), 37 transfer RNA (tRNAs), and 8 ribosome RNA (rRNAs). The evolutionary analysis used neighbour-joining (NJ) method and the result showed that E. buergerianum was closely related to Eriocaulon sexangulare in the family Eriocaulaceae. This study will be helpful for genome data and genomic resources of the family Eriocaulaceae for further.

Phylogenetic analysis and characterization of the complete chloroplast genome of Dipsacus asperoides, the endemic medicinal herb in China

Dipsacus asperoides is a traditional and endemic medicinal herb in China. Its roots was considered top grade herb as early as in the Shen Nong Herbal Classic. In this study, we assembled and analyzed the complete chloroplast genome of D. asperoides. The complete chloroplast genome is 160,481 bp in length, exhibiting a large single-copy region (88,546 bp), a small single-copy region (19,671 bp), and two inverted-repeat regions (26,132 bp in each one). The chloroplast genome of D. asperoides contains 133 genes, including 89 protein-coding genes (PCGs), 36 transfer RNA (tRNAs), and eight ribosome RNA (rRNAs). The overall nucleotide content of the chloroplast genome is A of 30.2%, T of 31.0%, C of 19.7%, and G of 19.1%, with a total AT content of 61.2% and GC content of 38.8%. However, the phylogenetic Maximum-Likelihood (ML) analysis based on the amino acid sequences of 89 PCGs from 14 species chloroplast genome that D. asperoides is closely related to Dipsacus asper. This study can be used for medicinal herb value research and clinical drug development.

Characterization of the chloroplast genome of the family Lauraceae plant species, Cinnamomum cassia

The fruit of Cinnamomum cassia is an important spice material and its branch is a common Chinese herbal medicine as the family Lauraceae. In this study, we reported the complete chloroplast genome of C. cassia. The chloroplast genome of C. cassia with length of 152,675 bp is a characteristic quadripartite structure. The length of the inverted-repeats regions (IRs), large single-copy (LSC) region, and small single-copy (SSC) region of C. cassia was 20,068 bp, 93,663 and 18,876 bp. The chloroplast genome of C. cassia contains 124 genes, which includes 80 protein-coding genes (PCGs), 36 transfer RNA genes (tRNAs) and 8 ribosomal RNA genes (rRNAs). The overall nucleotide content of the chloroplast genome: 30.0% A (Adenine), 30.8% T (Thymine), 19.7% C (Cytosine), 19.5% G (Guanine), and 39.2% GC content. Evolutionary relationship result showed that Cinnamomum cassia was most closely related to Cinnamomum parthenoxylon in the family Lauraceae by the Neighbor-Joining (NJ) method.

Cardiac Metabolic Limitations Contribute to Diminished Performance of the Heart in Aging

Changes in the myocardial energetics associated with aging—reductions in creatine phosphate/ATP ratio, total creatine, and ATP—mirror changes observed in failing hearts compared to healthy controls. Similarly, both aging and heart failure are associated with significant reductions in cardiac performance and maximal left ventricular cardiac power output compared with young healthy individuals. Based on these observations, we hypothesize that reductions in the concentrations of cytoplasmic adenine nucleotide, creatine, and phosphate pools that occur with aging impair the myocardial capacity to synthesize ATP at physiological free energy levels and that the resulting changes to myocardial energetic status impair the mechanical pumping ability of the heart. The purpose of this study is to test these hypotheses using an age-structured population model for myocardial metabolism in the adult female population and to determine the potential impact of reductions in key myocardial metabolite pools in causing metabolic/energetic and cardiac mechanical dysfunction associated with aging. To test these hypotheses, we developed a population model for myocardial energetics to predict myocardial ATP, ADP, creatine phosphate, creatine, and inorganic phosphate concentrations as functions of cardiac work and age in the adult female population. Model predictions support our hypotheses and are consistent with previous experimental observations. The major findings provide a novel, to our knowledge, theoretical and computational framework for further probing complex relationships between the energetics and performance of the heart with aging.