An Unusual Case of a Primary Hyperparathyroidism Mimic.

A 32-year-old lady with a history of bulimia nervosa was noted to have a raised adjusted calcium of 2.94mmol/L associated with high parathyroid hormone (PTH) 17.2pmol/L. On review, she had an apparent hypercalcaemia for at least three years, and also had a chronic, severe alkalosis with a bicarbonate up to 81.9mEQ/L. Ionised calcium during that time had actually been low, down to 1.03mmol/L. This case highlights the effects of alkalosis on calcium, as more albumin is available for binding to ionised calcium. This results in a low ionised calcium, which triggers PTH release and overall leads to raised adjusted calcium levels. Clinicians may misdiagnose a similar patient with primary hyperparathyroidism and treatment would cause worsening of true hypocalcaemia.

GlyNAC Supplementation Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Aging Hallmarks, Metabolic Defects, Muscle Strength, Cognitive Decline, and Body Composition: Implications for Healthy Aging.

Cellular increases in oxidative stress (OxS) and decline in mitochondrial function are identified as key defects in aging, but underlying mechanisms are poorly understood and interventions are lacking. Defects linked to OxS and impaired mitochondrial fuel oxidation, such as inflammation, insulin resistance, endothelial dysfunction, and aging hallmarks, are present in older humans and are associated with declining strength and cognition, as well as the development of sarcopenic obesity. Investigations on the origins of elevated OxS and mitochondrial dysfunction in older humans led to the discovery that deficiencies of the antioxidant tripeptide glutathione (GSH) and its precursor amino acids glycine and cysteine may be contributory. Supplementation with GlyNAC (combination of glycine and N-acetylcysteine as a cysteine precursor) was found to improve/correct cellular glycine, cysteine, and GSH deficiencies; lower OxS; and improve mitochondrial function, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, and multiple aging hallmarks; and improve muscle strength, exercise capacity, cognition, and body composition. This review discusses evidence from published rodent studies and human clinical trials to provide a detailed summary of available knowledge regarding the effects of GlyNAC supplementation on age-associated defects and aging hallmarks, as well as discussing why GlyNAC supplementation could be effective in promoting healthy aging. It is particularly exciting that GlyNAC supplementation appears to reverse multiple aging hallmarks, and if confirmed in a randomized clinical trial, it could introduce a transformative paradigm shift in aging and geriatrics. GlyNAC supplementation could be a novel nutritional approach to improve age-associated defects and promote healthy aging, and existing data strongly support the need for additional studies to explore the role and impact of GlyNAC supplementation in aging.

Treatment of dyslipidemia in HIV.

Patients infected with HIV have a high risk of developing dyslipidemia. Effective therapeutic strategies can be challenging due to an increase risk of drug interactions and other comorbidities. Understanding the underlying pathophysiology and the principles of pharmacological and non-pharmacological therapeutic interventions can be of value in the appropriate management of dyslipidemia in the HIV-infected patient.

Relationship of ethnicity and CD4 Count with glucose metabolism among HIV patients on Highly-Active Antiretroviral Therapy (HAART).

BACKGROUND: HIV patients on HAART are prone to metabolic abnormalities, including insulin resistance, lipodystrophy and diabetes. This study purports to investigate the relationship of ethnicity and CD4+ T cell count attained after stable highly-active antiretroviral treatment (HAART) with glucose metabolism in hyperrtriglyceridemic HIV patients without a history of diabetes. METHODS: Demographic, anthropometric, clinical, endocrinologic, energy expenditure and metabolic measures were obtained in 199 multiethnic, healthy but hypertriglyceridemic HIV-infected patients [46% Hispanic, 17% African-American, 37% Non-Hispanic White (NHW)] on stable HAART without a history of diabetes. The relationship of glucose and insulin responses to ethnicity, CD4 strata (low (<300/cc) or moderate-to-high (≥ 300/cc)), and their interaction was determined. RESULTS: African-Americans had significantly greater impairment of glucose tolerance (P < 0.05) and HbA1c levels (P < .001) than either Hispanics or NHWs. In multivariate models, after adjusting for confounders (age, sex, HIV/HAART duration, smoking, obesity, glucose, insulin and lipids), African-Americans and Hispanics had significantly higher HbA1c and 2-hour glucose levels than NHW's. Demonstrating a significant interaction between ethnicity and CD4 count (P = 0.023), African Americans with CD4 <300/cc and Hispanics with CD4 ≥300/cc had the most impaired glucose response following oral glucose challenge. CONCLUSIONS: Among hypertriglyceridemic HIV patients on HAART, African-Americans and Hispanics are at increased risk of developing diabetes. Ethnicity also interacts with CD4+ T cell count attained on stable HAART to affect post-challenge glycemic response.

GlyNAC (Glycine and N-Acetylcysteine) Supplementation in Old Mice Improves Brain Glutathione Deficiency, Oxidative Stress, Glucose Uptake, Mitochondrial Dysfunction, Genomic Damage, Inflammation and Neurotrophic Factors to Reverse Age-Associated Cognitive Decline: Implications for Improving Brain Health in Aging.

Cognitive decline frequently occurs with increasing age, but mechanisms contributing to age-associated cognitive decline (ACD) are not well understood and solutions are lacking. Understanding and reversing mechanisms contributing to ACD are important because increased age is identified as the single most important risk factor for dementia. We reported earlier that ACD in older humans is associated with glutathione (GSH) deficiency, oxidative stress (OxS), mitochondrial dysfunction, glucose dysmetabolism and inflammation, and that supplementing GlyNAC (glycine and N-acetylcysteine) improved these defects. To test whether these defects occur in the brain in association with ACD, and could be improved/reversed with GlyNAC supplementation, we studied young (20-week) and old (90-week) C57BL/6J mice. Old mice received either regular or GlyNAC supplemented diets for 8 weeks, while young mice received the regular diet. Cognition and brain outcomes (GSH, OxS, mitochondrial energetics, autophagy/mitophagy, glucose transporters, inflammation, genomic damage and neurotrophic factors) were measured. Compared to young mice, the old-control mice had significant cognitive impairment and multiple brain defects. GlyNAC supplementation improved/corrected the brain defects and reversed ACD. This study finds that naturally-occurring ACD is associated with multiple abnormalities in the brain, and provides proof-of-concept that GlyNAC supplementation corrects these defects and improves cognitive function in aging.

Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial.

BACKGROUND: Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial. METHODS: Twenty-four OA and 12 young adults (YA) were studied. OA was randomized to receive either GlyNAC (N = 12) or isonitrogenous alanine placebo (N = 12) for 16-weeks; YA (N = 12) received GlyNAC for 2-weeks. Participants were studied before, after 2-weeks, and after 16-weeks of supplementation to assess GSH concentrations, OxS, MFO, molecular regulators of energy metabolism, inflammation, endothelial function, IR, aging hallmarks, gait speed, muscle strength, 6-minute walk test, body composition, and blood pressure. RESULTS: Compared to YA, OA had GSH deficiency, OxS, mitochondrial dysfunction (with defective molecular regulation), inflammation, endothelial dysfunction, IR, multiple aging hallmarks, impaired physical function, increased waist circumference, and systolic blood pressure. GlyNAC (and not placebo) supplementation in OA improved/corrected these defects. CONCLUSION: GlyNAC supplementation in OA for 16-weeks was safe and well-tolerated. By combining the benefits of glycine, NAC and GSH, GlyNAC is an effective nutritional supplement that improves and reverses multiple age-associated abnormalities to promote health in aging humans. Clinical Trials Registration Number: NCT01870193.

KAP study conducted to assess the impact of special health education campaign for control of dengue at Vellore in Tamil Nadu.

An abnormal increase in the incidence of dengue was reported at Vellore Corporation since September 2012. Intensive control operations supported with health education campaigns were carried out from September to November 2012 till the outbreak situation subsided. During December 2012, a cross sectional survey was conducted at Vellore Corporation to assess the impact of the health education campaigns on the knowledge, attitude and practice in the community and also to assess future needs. A total of 101 families from four different locations at Vellore corporation were interviewed on pre-structured formats. Though 80% of the respondents felt that dengue could be effectively prevented and controlled only with community participation, majority of them lacked awareness on the day time biting behaviour of Aedes mosquitos, their indoor resting and breeding habits and relevance of specific control measures focused on the bionomics of dengue vectors.

GlyNAC (Glycine and N-Acetylcysteine) Supplementation Improves Impaired Mitochondrial Fuel Oxidation and Lowers Insulin Resistance in Patients with Type 2 Diabetes: Results of a Pilot Study.

Patients with type 2 diabetes (T2D) are known to have mitochondrial dysfunction and increased insulin resistance (IR), but the underlying mechanisms are not well understood. We reported previously that (a) adequacy of the antioxidant glutathione (GSH) is necessary for optimal mitochondrial fatty-acid oxidation (MFO); (b) supplementing the GSH precursors glycine and N-acetylcysteine (GlyNAC) in mice corrected GSH deficiency, reversed impaired MFO, and lowered oxidative stress (OxS) and IR; and (c) supplementing GlyNAC in patients with T2D improved GSH synthesis and concentrations, and lowered OxS. However, the effect of GlyNAC on MFO, MGO (mitochondrial glucose oxidation), IR and plasma FFA (free-fatty acid) concentrations in humans with T2D remains unknown. This manuscript reports the effect of supplementing GlyNAC for 14-days on MFO, MGO, IR and FFA in 10 adults with T2D and 10 unsupplemented non-diabetic controls. Fasted T2D participants had 36% lower MFO (p < 0.001), 106% higher MGO (p < 0.01), 425% higher IR (p < 0.001) and 76% higher plasma FFA (p < 0.05). GlyNAC supplementation significantly improved fasted MFO by 30% (p < 0.001), lowered MGO by 47% (p < 0.01), decreased IR by 22% (p < 0.01) and lowered FFA by 25% (p < 0.01). These results provide proof-of-concept that GlyNAC supplementation could improve mitochondrial dysfunction and IR in patients with T2D, and warrant additional research.

'Analogy-Based Comprehensive Diabetes Education' (ABCDE) Improves Glycemic Control of Diabetic Patients in an Underserved Population: Results of a Retrospective Chart Analysis.

Diabetes is the leading global cause for blindness, kidney failure and amputations. Preventing these complications requires optimal glycemic control, and it is imperative that diabetic patients understand the fundamental concepts of diabetes care. Although patients attend formal diabetes education classes, many do not comprehend basic concepts of diabetes, and are often noncompliant with diet, exercise and medications. A novel approach termed 'analogy-based comprehensive diabetes education' (ABCDE) was developed to educate HIV-patients with diabetes about basic concepts of diabetes care. The object of this manuscript is to report the results of a retrospective chart review on the impact of ABCDE on glycemic outcomes in 24 patients who had failed usual care (including formal diabetes education, physician visits, and diabetic medications), and were non-adherent with diet and medications. They received only the ABCDE without any changes in pharmacotherapy. The impact on glycosylated hemoglobin (HbA1c) and fasting blood glucose (FBG) was assessed at subsequent visits. HbA1c was found to decline by 22% and 33% after 3 and 6 months, respectively, with corresponding declines in FBG by 53% and 59%, respectively. These results suggest that ABCDE in outpatient diabetes clinics could be effective in behavior modification toward improving glycemic control, and warrants additional investigation.

GlyNAC (Glycine and N-Acetylcysteine) Supplementation in Mice Increases Length of Life by Correcting Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Abnormalities in Mitophagy and Nutrient Sensing, and Genomic Damage.

Determinants of length of life are not well understood, and therefore increasing lifespan is a challenge. Cardinal theories of aging suggest that oxidative stress (OxS) and mitochondrial dysfunction contribute to the aging process, but it is unclear if they could also impact lifespan. Glutathione (GSH), the most abundant intracellular antioxidant, protects cells from OxS and is necessary for maintaining mitochondrial health, but GSH levels decline with aging. Based on published human studies where we found that supplementing glycine and N-acetylcysteine (GlyNAC) improved/corrected GSH deficiency, OxS and mitochondrial dysfunction, we hypothesized that GlyNAC supplementation could increase longevity. We tested our hypothesis by evaluating the effect of supplementing GlyNAC vs. placebo in C57BL/6J mice on (a) length of life; and (b) age-associated GSH deficiency, OxS, mitochondrial dysfunction, abnormal mitophagy and nutrient-sensing, and genomic-damage in the heart, liver and kidneys. Results showed that mice receiving GlyNAC supplementation (1) lived 24% longer than control mice; (2) improved/corrected impaired GSH synthesis, GSH deficiency, OxS, mitochondrial dysfunction, abnormal mitophagy and nutrient-sensing, and genomic-damage. These studies provide proof-of-concept that GlyNAC supplementation can increase lifespan and improve multiple age-associated defects. GlyNAC could be a novel and simple nutritional supplement to improve lifespan and healthspan, and warrants additional investigation.

Severe Glutathione Deficiency, Oxidative Stress and Oxidant Damage in Adults Hospitalized with COVID-19: Implications for GlyNAC (Glycine and N-Acetylcysteine) Supplementation.

Humanity is battling a respiratory pandemic pneumonia named COVID-19 which has resulted in millions of hospitalizations and deaths. COVID-19 exacerbations occur in waves that continually challenge healthcare systems globally. Therefore, there is an urgent need to understand all mechanisms by which COVID-19 results in health deterioration to facilitate the development of protective strategies. Oxidative stress (OxS) is a harmful condition caused by excess reactive-oxygen species (ROS) and is normally neutralized by antioxidants among which Glutathione (GSH) is the most abundant. GSH deficiency results in amplified OxS due to compromised antioxidant defenses. Because little is known about GSH or OxS in COVID-19 infection, we measured GSH, TBARS (a marker of OxS) and F2-isoprostane (marker of oxidant damage) concentrations in 60 adult patients hospitalized with COVID-19. Compared to uninfected controls, COVID-19 patients of all age groups had severe GSH deficiency, increased OxS and elevated oxidant damage which worsened with advancing age. These defects were also present in younger age groups, where they do not normally occur. Because GlyNAC (combination of glycine and N-acetylcysteine) supplementation has been shown in clinical trials to rapidly improve GSH deficiency, OxS and oxidant damage, GlyNAC supplementation has implications for combating these defects in COVID-19 infected patients and warrants urgent investigation.

Glycine and N-acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: Results of a pilot clinical trial.

BACKGROUND: Oxidative stress (OxS) and mitochondrial dysfunction are implicated as causative factors for aging. Older adults (OAs) have an increased prevalence of elevated OxS, impaired mitochondrial fuel-oxidation (MFO), elevated inflammation, endothelial dysfunction, insulin resistance, cognitive decline, muscle weakness, and sarcopenia, but contributing mechanisms are unknown, and interventions are limited/lacking. We previously reported that inducing deficiency of the antioxidant tripeptide glutathione (GSH) in young mice results in mitochondrial dysfunction, and that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improves naturally-occurring GSH deficiency, mitochondrial impairment, OxS, and insulin resistance. This pilot trial in OA was conducted to test the effect of GlyNAC supplementation and withdrawal on intracellular GSH concentrations, OxS, MFO, inflammation, endothelial function, genotoxicity, muscle and glucose metabolism, body composition, strength, and cognition. METHODS: A 36-week open-label clinical trial was conducted in eight OAs and eight young adults (YAs). After all the participants underwent an initial (pre-supplementation) study, the YAs were released from the study. OAs were studied again after GlyNAC supplementation for 24 weeks, and GlyNAC withdrawal for 12 weeks. Measurements included red-blood cell (RBC) GSH, MFO; plasma biomarkers of OxS, inflammation, endothelial function, glucose, and insulin; gait-speed, grip-strength, 6-min walk test; cognitive tests; genomic-damage; glucose-production and muscle-protein breakdown rates; and body-composition. RESULTS: GlyNAC supplementation for 24 weeks in OA corrected RBC-GSH deficiency, OxS, and mitochondrial dysfunction; and improved inflammation, endothelial dysfunction, insulin-resistance, genomic-damage, cognition, strength, gait-speed, and exercise capacity; and lowered body-fat and waist-circumference. However, benefits declined after stopping GlyNAC supplementation for 12 weeks. CONCLUSIONS: GlyNAC supplementation for 24-weeks in OA was well tolerated and lowered OxS, corrected intracellular GSH deficiency and mitochondrial dysfunction, decreased inflammation, insulin-resistance and endothelial dysfunction, and genomic-damage, and improved strength, gait-speed, cognition, and body composition. Supplementing GlyNAC in aging humans could be a simple and viable method to promote health and warrants additional investigation.

A study on the resting preference of mosquito species in wells in Vellore in Tamilnadu, South India.

The resting preferences of mosquito species was investigated in domestic wells. In addition to the routine adult surveys in human dwellings, adult collections were also made in domestic wells using an innovated equipment operating on the principles of spray sheet collections. Above the water surface, wells provide humid and dark microclimate along the inner walls. It has been observed that this microclimate provides very congenial resting place for few mosquito species; specially for the males and for the females between their gonotropic cycles. Larval collections in the wells did not reveal breeding of majority of the mosquito species collected by this technique. Investigations were conducted in 87 wells in 11 localities during 2005. A total of 4969 mosquitos were collected of which 69.1% (3441) were males and 30.9% (1528) were females. From among the mosquitos collected 96.5% were Cu. quinquifasciatus, 0.26% All stephensi, 3.0% Aedes agypti and 0.24% Armegeres sp. The results of the analysis of the physical and chemical parameter of water samples of the study wells before and after the surveys endorsed the utility of this technique for entomological investigations in outbreak situations, for monitoring the liquidation of outbreak foci and for other research purposes.

Supplementing Glycine and N-acetylcysteine (GlyNAC) in Aging HIV Patients Improves Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Endothelial Dysfunction, Insulin Resistance, Genotoxicity, Strength, and Cognition: Results of an Open-Label Clinical Trial.

Background: Patients with HIV (PWH) develop geriatric comorbidities, including functional and cognitive decline at a younger age. However, contributing mechanisms are unclear and interventions are lacking. We hypothesized that deficiency of the antioxidant protein glutathione (GSH) contributes to multiple defects representing premature aging in PWH, and that these defects could be improved by supplementing the GSH precursors glycine and N-acetylcysteine (GlyNAC). Methods: We conducted an open label clinical trial where eight PWH and eight matched uninfected-controls were studied at baseline. PWH were studied again 12-weeks after receiving GlyNAC, and 8-weeks after stopping GlyNAC. Controls did not receive supplementation. Outcome measures included red-blood cell and muscle GSH concentrations, mitochondrial function, mitophagy and autophagy, oxidative stress, inflammation, endothelial function, genomic damage, insulin resistance, glucose production, muscle-protein breakdown rates, body composition, physical function and cognition. Results: PWH had significant defects in measured outcomes, which improved with GlyNAC supplementation. However, benefits receded after stopping GlyNAC. Conclusions: This open label trial finds that PWH have premature aging based on multiple biological and functional defects, and identifies novel mechanistic explanations for cognitive and physical decline. Nutritional supplementation with GlyNAC improves comorbidities suggestive of premature aging in PWH including functional and cognitive decline, and warrants additional investigation.

Simulating coconut growth, development and yield with the InfoCrop-coconut model.

Simulation modeling of perennial crops has immense potential for generating information for plantation managers. We report the development of the InfoCrop-coconut model and its application to coconut (Cocos nucifera L.) growing in diverse tropical and subtropical environments. The model is based on the generic crop model InfoCrop that simulates various annual crops in tropical and subtropical regions. The InfoCrop-coconut model was calibrated and validated with data compiled from published studies comprising many physiological, agronomical and nutritional experiments conducted between 1978 and 2005 in diverse geographic locations throughout India. The treatments included various water and nutrient regimes and varieties of coconut. Time to first flowering varied between 4 and 6 years, leaf production varied from 8 to 15 leaves year(-1) and nut yield ranged from 3000 to 27,000 nuts ha(-1) year(-1). The genetic coefficients used for calibration and validation were generated from field experiments conducted during 1995-2005. Model efficiency and validation performance were analyzed statistically. Simulated trends in phenological development, total dry mass and its partitioning, and nut yield agreed closely with observed values, although a 15% error was observed in a few cases. Considering that field measurements have an experimental error of 10-15% and wide variation existed within treatments, the model adequately simulated the effects of management practices and agro-climatic conditions over short periods. For a range of agro-climatic zones, simulated potential yields varied from 26 to 30 Mg ha(-1) year(-1) and potential annual dry mass production varied from 52 to 62 Mg ha(-1), depending on environment. We conclude that InfoCrop-coconut can be used to increase the efficiency of agronomic experiments designed to aid coconut crop management.

A biomechanical model of mammographic compressions.

A number of biomechanical models have been proposed to improve nonrigid registration techniques for multimodal breast image alignment. A deformable breast model may also be useful for overcoming difficulties in interpreting 2D X-ray projections (mammograms) of 3D volumes (breast tissues). If a deformable model could accurately predict the shape changes that breasts undergo during mammography, then the model could serve to localize suspicious masses (visible in mammograms) in the unloaded state, or in any other deformed state required for further investigations (such as biopsy or other medical imaging modalities). In this paper, we present a validation study that was conducted in order to develop a biomechanical model based on the well-established theory of continuum mechanics (finite elasticity theory with contact mechanics) and demonstrate its use for this application. Experimental studies using gel phantoms were conducted to test the accuracy in predicting mammographic-like deformations. The material properties of the gel phantom were estimated using a nonlinear optimization process, which minimized the errors between the experimental and the model-predicted surface data by adjusting the parameter associated with the neo-Hookean constitutive relation. Two compressions (the equivalent of cranio-caudal and medio-lateral mammograms) were performed on the phantom, and the corresponding deformations were recorded using a MRI scanner. Finite element simulations were performed to mimic the experiments using the estimated material properties with appropriate boundary conditions. The simulation results matched the experimental recordings of the deformed phantom, with a sub-millimeter root-mean-square error for each compression state. Having now validated our finite element model of breast compression, the next stage is to apply the model to clinical images.

Myxoid adrenal adenoma with focal pseudoglandular pattern.

Adrenal cortical tumors with myxoid change are rare tumors. To our knowledge, only 22 cases have been described so far in literature, which include 13 carcinomas and 9 adenomas. A pseudoglandular pattern has been described in 9 of these tumors. We report a case of a myxoid adenoma of the left adrenal gland in a 67-year-old woman, with a focal pseudoglandular pattern involving about 20% of the studied tumor. Rest of the tumor was composed of anastomosing cords of tumor cells. Abundant myxoid stroma was present, which stained positively with alcian blue and was weakly focally positive with periodic acid Schiff. Immunophenotype was consistent with an adrenal tumor, i.e., positive for vimentin, inhibin, and melan A. Cytokeratin AE1/AE3 and chromogranin were negative. MIB-1 index was < 0.1%.

Improved Cardiovascular Function in Old Mice After N-Acetyl Cysteine and Glycine Supplemented Diet: Inflammation and Mitochondrial Factors.

Metabolic, inflammatory, and functional changes occur in cardiovascular aging which may stem from oxidative stress and be remediable with antioxidants. Glutathione, an intracellular antioxidant, declines with aging, and supplementation with glutathione precursors, N-acetyl cysteine (NAC) and glycine (Gly), increases tissue glutathione. Thirty-month old mice were fed diets supplemented with NAC or NAC+Gly and, after 7 weeks, cardiac function and molecular studies were performed. The NAC+Gly supplementation improved diastolic function, increasing peak early filling velocity, and reducing relaxation time, left atrial volume, and left ventricle end diastolic pressure. By contrast, cardiac function did not improve with NAC alone. Both diet supplementations decreased cardiac levels of inflammatory mediators; only NAC+Gly reduced leukocyte infiltration. Several mitochondrial genes reduced with aging were upregulated in hearts by NAC+Gly diet supplementation. These Krebs cycle and oxidative phosphorylation enzymes, suggesting improved mitochondrial function, and permeabilized cardiac fibers from NAC+Gly-fed mice produced ATP from carbohydrate and fatty acid sources, whereas fibers from control old mice were less able to utilize fatty acids. Our data indicate that NAC+Gly supplementation can improve diastolic function in the old mouse and may have potential to prevent important morbidities for older people.