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Adequate protein intakes are important for preventing and treating sarcopenia. Age-related sarcopenia is associated with altered physical functioning, and hyperglycemia is associated with an increased risk for sarcopenia, possibly due to increased muscle loss related to metabolic changes. Impairments in physical functioning may be manifested as falls, fractures, and limited mobility. Therefore, this study examined the differences in physical functioning in U.S. adults by glycemic status and protein intake. Data were examined from 23,487 non-institutionalized adults, aged 31 years and older, from the 2005-2016 National Health and Nutrition Examination Survey (NHANES). Hemoglobin A1c (%) was used to classify glycemic status: nondiabetes ( Disclosure S. Thomas: Employee; Self; Abbott. S.M. Fanelli: None. O. Kelly: Employee; Self; Abbott. Employee; Spouse/Partner; Abbott. J.L. Krok-Schoen: None. C.A. Taylor: Research Support; Self; Abbott Laboratories. Funding Abbott Nutrition

Hyperglycemia is associated with an increased risk for sarcopenia. The concurrence of hyperglycemia and sarcopenia may inflate the risk for falls, fractures, and mortality. On average, Americans consume more than the individual protein recommendation (0.8 g/kg/d); however, a large proportion of adults still consume less than recommended levels, which may have negative health implications. Therefore, this study examined the individual protein intake in a nationally representative sample of adults (31+ years) with and without type 2 diabetes to explore protein intakes (g/d) and diet quality (Healthy Eating Index-2015). Data were examined from 23,487 non-institutionalized adults from the 2005-2016 National Health and Nutrition Examination Survey (NHANES). Hemoglobin A1c (%) was used to classify glycemic status: nondiabetes ( Disclosure S. Thomas: Employee; Self; Abbott. S.M. Fanelli: None. O. Kelly: Employee; Self; Abbott. Employee; Spouse/Partner; Abbott. J.L. Krok-Schoen: None. C.A. Taylor: Research Support; Self; Abbott Laboratories. Funding Abbott Nutrition

OBJECTIVES: Diabetes and prediabetes are a major public health concern in the United States. It is unknown how food-related behaviors are influenced by diabetes status. Therefore this study assessed the association between diabetes status and food behaviors (meal preparation, food procurement, and food spending) among U.S. adults. METHODS: Data from 8799 adults from the 2005–2016 National Health and Nutrition Examination Survey were categorized by glycated hemoglobin levels (A1c%): nondiabetes (6.5%; n = 1071). A1c levels were compared with meal preparation, food procurement, and spending data. Age-adjusted analyses for total and by sex (n = 4481 females and n = 4318 males) were performed. RESULTS: All adults (P = 0.002) and males (P = 0.001) with diabetes and prediabetes spent less money dining out than those without diabetes. Those with diabetes had a significantly further distance to grocery stores among the adult (P = 0.018) and male samples (P = 0.032). Females with diabetes spent more on carryout/delivered foods (P = 0.025) and ate fewer meals per week with family (P = 0.039) than those without diabetes. Females with diabetes were less likely to serve as the main food shoppers (P = 0.012) and males with diabetes were less likely to share meal planning/preparation responsibilities (P = 0.034). CONCLUSIONS: Diabetes status associates with meal preparation, food procurement, and spending behaviors, and differs for males and females. These findings support the importance of addressing the behavioral context of food choices to help support a healthier diet and lifestyle for all adults. FUNDING SOURCES: Abbott Nutrition.

OBJECTIVES: Distribution of carbohydrate intakes (carb choices) throughout the day are an important aspect to diabetes management and reducing blood glucose spikes. Skipping breakfast represents a behavior of concern, providing an extension of the overnight fast and may result in elevated sugar levels later in the day. Therefore, the purpose of this study was to evaluate dietary intake differences, including carbohydrates, based on consuming breakfast or not, and by diabetes status. METHODS: Adults over 30 years from NHANES 2005–2016 were classified into nondiabetes (HbA1c

Background: Osteosarcopenic obesity, the combined deterioration of bone, muscle and fat tissues, could become the ultimate trajectory of aging. Aging stem cells are deregulated by low-grade chronic inflammation and possibly by diet. The metabolic shift of stem cells towards adipogenesis results in osteo obesity, sarco obesity and obesity. Macronutrients have numerous physiological functions but are regarded mainly for their energy contribution. Currently, no nutritional causes or treatment/prevention guidelines exist for osteosarcopenic obesity. Objective: The aim of this review is to assemble the evidence to elucidate if the macronutrient composition of the Western diet has an effect on the development of osteosarcopenic obesity. In view of the role of brain in locomotion a section examining the macronutrients as possible modulators of brain functioning was included. Method: An extensive literature search of PubMed and Medline was conducted for human data using combinations and synonyms of osteoporosis, sarcopenia and obesity, and energy, carbohydrate, protein and lipid, and brain. US National Health and Nutrition Examination Survey (NHANES) food intake data from 2002-2012 were obtained and transposed to Microsoft Excel for analysis. Results: NHANES data showed that energy imbalances in aging, excess high glycemic carbohydrate, lower protein intakes and low long chain polyunsaturated fat intakes may contribute to osteosarcopenic obesity. 135 articles were included in the review. Conclusion: Early humans probably consumed a diet closer to what the human body was designed for; however, we do not know the ideal energy and macronutrient proportions for optimal health or for preventing/treating aging and osteosarcopenic obesity.

Osteosarcopenic obesity syndrome (OSO) has recently been identified as a condition encompassing osteopenia/osteoporosis, sarcopenia and obesity. OSO is especially deleterious in older adults (even if they are not obese by conventional measures), due to age-related redistribution of fat and its infiltration into bone and muscle. Osteoporosis and bone fractures in elderly increase the risk of sarcopenia, which, through decreased mobility, increases the risk of more falls and fractures, creating a vicious cycle. Obesity plays a dual role: to a certain extent, it promotes bone and muscle gains through mechanical loading; in contrast, increased adiposity is also a source of pro-inflammatory cytokines and other endocrine factors that impair bone and muscle. As the elderly population increases, changes in lifestyle to delay the onset of OSO, or prevent OSO, are warranted. Among these changes, dietary patterns and physical activity modifications are the first ones to be implemented. The typical Western diet (and lifestyle) promotes several chronic diseases including OSO, by facilitating a pro-inflammatory state, largely via the imbalance in omega-6/omega-3 fatty acid ratio and low-fiber and high-processed food consumption. Nutritional modifications to prevent and/or alleviate the OSO syndrome include adequate intake of protein, calcium, magnesium and vitamin D and increasing consumptions of foods containing omega-3 polyunsaturated fatty acids and fiber. Certain types of physical activity, often decreased in overweight/obese women and in elderly, might preserve bone and muscle, as well as help in reducing body fat accrual and fat infiltration. Habitual daily activities and some alternative modes of exercise may be more appropriate for older adults and play a crucial role in preventing bone and muscle loss and maintaining optimal weight. In conclusion, older adults who suffer from OSO syndrome may benefit from combined efforts to improve diet and physical activity, and such recommendations should be fostered as part of public health programs.

The present study investigated the meal patterns across demographic characteristics in middle-aged and older US adults. Study participants were noninstitutionalized participants from the 2005&ndash, 2016 National Health and Nutrition Examination Survey, an observational cross-sectional study. Data from 17,361 adults were categorized into 45&ndash, 59 years (n = 7366), 60&ndash, 70 years (n = 5348), and 71+ years (n = 4647) to compare demographics, nutrient intakes, and meal patterns. Dietary recalls were collected using the multiple-pass method. Data analyses were weighted to create a nationally representative sample. Two-thirds of adults reported consuming three meals on the day of intake. Lunch was the most often skipped meal across all age groups. A greater proportion of adults over 70 years reported consuming breakfast, while a smaller proportion reported consuming snacks. Significant differences were observed in total energy and nutrient intakes and proportion of the day&rsquo, s intakes by meal. Grain, milk, and dairy food group intakes were highest at breakfast, while the protein food group intakes were highest at lunch and dinner. Age-related differences in meal consumption and composition provide valuable formative data to support targeted nutritional education and intervention opportunities to promote and encourage healthy food choices.

Skipping breakfast is considered an unhealthy behavior and has been associated with an increased risk of diabetes and poor glycemic control in people with diabetes. Little is known regarding the impact of breakfast skipping on daily energy and nutrient intakes, as well as at eating occasions in people with versus without diabetes. National Health and Nutrition Examination Survey data (2005-16), and hemoglobin A1c data, were used to examine differences in dietary intakes of those who self-reported consuming or skipping breakfast. Adults over 30 years (n=23708) were stratified using A1c values into diabetes status: Disclosure O. Kelly: Employee; Self; Abbott. Employee; Spouse/Partner; Abbott. S.M. Fanelli: None. J.L. Krok-Schoen: None. C.A. Taylor: Consultant; Self; Abbott Laboratories. Research Support; Self; Abbott Laboratories. Other Relationship; Self; Elsevier. Funding Abbott Nutrition

Glycemic control greatly relies on total dietary and carbohydrate intakes, but more importantly the distribution of these intakes throughout the day. The purpose of this study was to understand meal and snack patterns and their contribution to the day’s intakes in people with and without diabetes. Meal and snack intakes were assessed for adults over 30 years of age (n=23708) using dietary and hemoglobin A1c data from the 2005-2016 National Health and Nutrition Examination Survey (NHANES). Dietary intakes were assessed from a 24-hour dietary recall. Participants self-reported meals and snacks. Intakes were aggregated to obtain nutrients consumed at meals and snacks and were used to compute the percent of the total day’s intakes contributed by each meal or snack. Participants were stratified into diabetes status using A1c values: 7% (poorly controlled diabetes, n=2021). Data were weighted to create a nationally representative sample. Significantly less adults with controlled and poorly controlled diabetes consumed all three meals per day (60-62%, P Disclosure O. Kelly: Employee; Self; Abbott. Employee; Spouse/Partner; Abbott. S.M. Fanelli: None. J.L. Krok-Schoen: None. C.A. Taylor: Consultant; Self; Abbott Laboratories. Research Support; Self; Abbott Laboratories. Other Relationship; Self; Elsevier. Funding Abbott Nutrition

Objective To investigate protein intakes across demographic characteristics in relation to dietary patterns and functional outcomes in older adults. Design Observational and cross-sectional study. Setting Non-institutionalized participants from the 2005–2014 National Health and Nutrition Examination Survey. Participants Data from 11,680 adults were categorized into 51–60 years (n= 4,016), 61–70 years (n=3,854), and 71 years and older (n=3,810) for analysis. Measurements Adults were stratified by meeting or not meeting the protein recommendation (0.8 g/kg/d) to compare demographics, diet quality with Healthy Eating Index– 2015, functional limitations, and other dietary intakes. Dietary recalls were collected using the multiple pass method. Data analyses were weighted to create a nationally–representative sample. Results Dietary protein intakes were significantly lower in older age groups, with up to 46% of the oldest adults not meeting the protein intake recommendation. Participants consuming protein below the recommended intake level had significantly poorer diet quality across all age groups (P

We recently showed that using micronutrient ratios in nutritional research might provide more insights into how diet affects metabolism and health outcomes, based on the notion that nutrients, unlike drugs, are not consumed one at a time and do not target a single metabolic pathway. In this paper, we present a concept of macronutrient ratios, including intra- and inter-macronutrient ratios. Macronutrient intakes from food only, from the What We Eat in America website (summarized National Health and Nutrition Examination Survey data) were transposed into Microsoft Excel to generate ratios. Overall, the dietary ratios of macronutrients may be more revealing and useful in epidemiology and in basic nutritional research than focusing on individual protein, fat, and carbohydrate intakes. While macronutrient ratios may be applied to all types of nutritional research, nutritional epidemiology, and, ultimately, dietary guidelines, the methodology required has not been established yet. In the meantime, intra- and inter-macronutrient ratios may serve as a measure of individual and total macronutrient quality.

Unhealthy lifestyle behaviors, including poor diet over many years, contribute to the development of chronic diseases, especially overweight/obesity, hyperglycemia, hypercholesterolemia and hypertension. Because poor diet is common to the diseases, it supports the notion of concurrently managing comorbidities through improved diet. Therefore, the purpose of this study was to assess differences in diet quality and nutrient intakes, in adults aged 65 years and older, by the number of chronic conditions. Data from 7,169 adults, aged 65 years and older, from the 2005-2016 National Health and Nutrition Examination Survey were assessed for selected chronic diseases from laboratory data: overweight/obesity (body mass index >25); hyperglycemia (glycated hemoglobin >5.7%); hypercholesterolemia (total cholesterol >200 mg/dL); hypertension (blood pressure >120/80 mmHg). The number of chronic diseases was computed per participant. Dietary intakes and diet quality score were assessed using 24-hour dietary recalls. Few adults had none of the selected chronic disease (n=79;1.4%), with others presenting 1 indicator (n=677;9.8%), 2 indicators (n=1,762;25%), 3 indicators (n=2,741;38.9%) and all 4 indicators (n=1,910;24.9%). Diet quality was significantly lower in those with three or four chronic diseases (P

Nutritional modification is a key consideration for the management of diabetes. Characterization of dietary habits among adults with diabetes may help focus dietary behavior changes. Dietary intakes and hemoglobin A1c data from the 2005-2014 National Health and Nutrition Examination Survey (NHANES) were evaluated to assess differences in meal and snacking macronutrient patterns by A1c levels. Data from 20,2adults ≥ 30 years were categorized into the following groups using A1c values: Disclosure O. Kelly: Employee; Self; Abbott. Employee; Spouse/Partner; Abbott. J.L. Krok-Schoen: None. M. Luo: Employee; Self; Abbott. C.A. Taylor: None.

Aging affects almost all physiological processes, but changes in body composition and body phenotype are most observable. In this review, we focus on these changes, including loss of bone and muscle and increase in body fat or redistribution of the latter, possibly leading to osteosarcopenic obesity syndrome. We also address low-grade chronic inflammation, prevalent in aging adults and a cause of many disorders including those associated with body composition. Changes in dietary intake and nutritional requirements of older individuals, that all may lead to some disturbances on tissue and organ levels, are discussed as well. Finally, we discuss the hormonal changes in the aging body, considering each of the tissues, bone, muscle and fat as separate endocrine organs, but yet in the continuous interface and communication with each other. Although there are still many unanswered questions in this field, this review will enable the readers to better understand the aging human body and measures needing to be implemented toward reducing impaired health and disability in older individuals.

Loss of muscle mass during periods of disuse likely has negative health consequences for older adults. We have previously shown that β-hydroxy-β-methylbutyrate (HMB) supplementation during 10 days of strict bed rest (BR) attenuates the loss of lean mass in older adults. To elucidate potential molecular mechanisms of HMB effects on muscle during BR and resistance training rehabilitation (RT), we examined mediators of skeletal muscle mitochondrial dynamics, autophagy and atrophy, and intramyocellular lipids. Nineteen older adults (60–76 yr) completed 10 days BR followed by 8-wk RT rehabilitation. Subjects were randomized to either HMB (3 g/day HMB; n = 11) or control (CON; n = 8) groups. Skeletal muscle cross-sectional area (CSA) was determined by histology from percutaneous vastus lateralis biopsies. We measured protein markers of mitochondrial content [oxidative phosphorylation (OXPHOS)], fusion and fission (MFN2, OPA1, FIS1, and DRP1), autophagy (Beclin1, LC3B, and BNIP3), and atrophy [poly-ubiquinated proteins (poly-ub)] by Western blot. Fatty acid composition of several lipid classes in skeletal muscle was measured by infusion-MS analysis. Poly-ub proteins and OXPHOS complex I increased in both groups following BR ( P < 0.05, main effect for time), and muscle triglyceride content tended to increase following BR in the HMB group ( P = 0.055). RT rehabilitation increased OXPHOS complex II protein ( P < 0.05), and total OXPHOS content tended ( P = 0.0504) to be higher in HMB group. In addition, higher levels of DRP1 and MFN2 were maintained in the HMB group after RT ( P < 0.05). BNIP3 and poly-ub proteins were significantly reduced following rehabilitation in both groups ( P < 0.05). Collectively, these data suggest that HMB influences mitochondrial dynamics and lipid metabolism during disuse atrophy and rehabilitation. NEW & NOTEWORTHY Mitochondrial content and dynamics remained unchanged over 10 days of BR in older adults. HMB stimulated intramuscular lipid storage as triacylglycerol following 10 days of bed rest (BR) and maintained higher mitochondrial OXPHOS content and dynamics during the 8-wk resistance exercise rehabilitation program.

Some of the universal characteristics of pre-agricultural hominin diets are strikingly different from the modern human diet. Hominin dietary choices were limited to wild plant and wild animal foods, while the modern diet includes more than 70 % of energy consumed from refined sugars, refined vegetable oils, and highly processed cereals and dairy products. The modern diet, with higher intake of fat has also resulted in a higher ratio of omega-6 (n-6) to omega-3 (n-3) polyunsaturated fatty acids (PUFA), contributing to low-grade chronic inflammation (LGCI) and thus promoting the development of many chronic diseases, including obesity and osteoporosis. In this review, we describe the changes in modern diet, focusing on the kind and amount of consumed fat; explain the shortcomings of the modern diet with regard to inflammatory processes; and delineate the reciprocity between adiposity and inflammatory processes, with inflammation being a common link between obesity and osteoporosis. We present the evidence that overconsumption of n-6 PUFA coupled with under-consumption of n-3 PUFA results in LGCI and, along with the increased presence of reactive oxygen species, leads to a shift in mesenchymal stem cells (precursors for both osteoblasts and adipocytes) lineage commitment toward increased adipogenesis and suppressed osteoblastogenesis. In turn, high n-6 to n-3 PUFA ratios in the modern diet, coupled with increased synthesis of pro-inflammatory cytokines due to adiposity, propagate obesity and osteoporosis by increasing or maintaining LGCI.

While sarcopenia and sarcopenic obesity have been recognized in the last decade, a combined concept to include decreased muscle mass and strength, as well as decreased bone mass with coexistence of adiposity is discussed here. We introduce a new term, osteopenic obesity, and operationalize its meaning within the context of osteopenia and obesity. Next, we consolidate osteopenic obesity with the already existing and more familiar term, sarcopenic obesity, and delineate the resulting combined condition assigning it the term osteosarcopenic obesity. Identification and possible diagnosis of each condition are discussed, as well as the interactions of muscle, fat and bone tissues on cellular level, considering their endocrine features. Special emphasis is placed on the mesenchymal stem cell commitment into osteoblastogenic, adipogenic and myogenic lineages and causes of its deregulation. Based on the presented evidence and as expounded within the text, it is reasonable to say that under certain conditions, osteoporosis and sarcopenia could be the obesity of bone and muscle, respectively, with the term osteosarcopenic obesity as an encompassment for all.

Several studies have investigated the possibility of dairy foods and calcium (Ca) mediating weight and body composition, but a consensus has not been reached. We aimed to investigate weight-loss-related outcomes during intervention with low-fat dairy foods or Ca + vitamin D supplements, both as complements to hypocaloric diets. Overweight/obese Caucasian, early-postmenopausal women (n = 135) were recruited for a 6 month energy-restricted weight loss study complemented with either low-fat dairy foods (D, 4&ndash, 5 servings/day), or Ca + vitamin D supplements (S), both to amount a total of ~1500 mg/day and 600 IU/day of Ca and vitamin D, respectively, or placebo pills (C). Bone mineral density (BMD) and lean and fat tissue were measured by Lunar iDXA. Serum and urinary markers of bone turnover were analyzed. Diet and physical activity were assessed with 3-day records. Participants on average lost ~4%, ~3%, and ~2% of body weight, fat, and lean tissue, respectively. The significantly better outcomes were noticed in participants in the D group regarding body composition (fat loss/lean tissue preservation) and in participants in the S group regarding the BMD outcomes, compared to those in the C group. Therefore, increasing low-fat dairy foods to 4&ndash, 5 servings/day and/or increasing Ca &amp, vitamin D intake by supplements (in those who are at the borderline dietary intake) may be beneficial for weight loss/maintenance and may lead to more favorable bone and body composition outcomes in postmenopausal women during moderate weight loss.

Whole fat milk and dairy products (although providing more energy compared to low- or non-fat products), are good sources of α-linolenic acid (ALA), conjugated linoleic acid (CLA) and calcium, which may be favorable in modulating bone and adipose tissue metabolism. We examined individual and/or synergistic effects of ALA, CLA and calcium (at levels similar to those in whole milk/dairy products) in regulating bone and adipose cell growth. ST2 stromal, MC3T3-L1 adipocyte-like and MC3T3-E1 osteoblast-like cells were treated with: (a) linoleic acid (LNA):ALA ratios = 1-5:1; (b) individual/combined 80-90 % c9, t11 (9,11) and 5-10 % t10, c12 (10,12) CLA isomers; (c) 0.5-3.0 mM calcium; (d) combinations of (a), (b), (c); and (e) control. Local mediators, including eicosanoids and growth factors, were measured. (a) The optimal effect was found at the 4:1 LNA:ALA ratio where insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3) production was the lowest in MC3T3-L1 cells. (b) All CLA isomer blends decreased MC3T3-L1 and increased MC3T3-E1 cell differentiation. (c) 1.5-2.5 mM calcium increased ST2 and MC3T3-E1, and decreased MC3T3-L1 cell proliferation. (d) Combination of 4:1 LNA:ALA + 90:10 % CLA + 2.0 mM calcium lowered MC3T3-L1 and increased MC3T3-E1 cell differentiation. Overall, the optimal LNA:ALA ratio to enhance osteoblastogenesis and inhibit adipogenesis was 4:1. This effect was enhanced by 90:10 % CLA + 2.0 mM calcium, indicating possible synergism of these dietary factors in promoting osteoblast and inhibiting adipocyte differentiation in cell cultures.

Background Body composition changes occur with aging; bone and muscle mass decrease while fat mass increases. The collective term for these changes is osteosarcopenic obesity. It is known that conventional resistance exercise programs build/maintain lean mass and reduce fat mass. However, unconventional (to Western society/medicine) forms of exercise may be viable for the treatment/prevention of osteosarcopenic obesity. Objective The purpose of this review is to assess relatively unconventional exercises for their efficacy in maintaining/improving bone and muscle mass and reducing fat mass. Method A literature search for unconventional exercise showed Tai Chi, yoga, Pilates, whole body vibration, electrical stimulation of muscle, and the Alexander Technique were considered alternative/ unconventional. A PubMed and Medline search for human data using combinations and synonyms of osteoporosis, sarcopenia and obesity, and each exercise was then conducted. Results Tai Chi, yoga, and Pilates, in addition to whole body vibration, electrical stimulation of muscle, and the Alexander Technique are all considered low impact. Tai Chi, yoga, and Pilates not only physically support the body, but also increase balance and quality of life. The devices showed promise in reducing or preventing muscle atrophy in older people that are unable to perform conventional exercises. Conclusion Any exercise, conventional or otherwise, especially in sedentary older people, at risk of, or diagnosed with osteosarcopenic obesity may be better than none. Exercise prescriptions should suit the patient and the desired outcomes; the patient should not be forced to fit an exercise prescription, so all potential forms of exercise should be considered.

Background: Aging, chronic inflammation and/or many chronic conditions may result in loss of bone, loss of muscle and increased adiposity, manifested either overtly (overweight) or furtively as fat infiltration into bone and muscle. This combined condition has been identified as osteosarcopenic obesity. Micronutrients are required, not just to prevent deficiency diseases, but for optimal health and metabolic homeostasis. Further, micronutrients have multifunctional roles in the body. However, it is unknown if the micronutrient intake of the Western diet contributes to bone and muscle loss, increased adiposity, and ultimately osteosarcopenic obesity. Objective: The aim of this review is to examine the micronutrient intake using US National Health and Nutrition Examination Survey (NHANES) data, and explore if the insufficiencies, or excesses present contribute to the development of osteosarcopenic obesity in aging. Method: First NHANES food intake data from 2002-2012 were obtained and transposed to Microsoft Excel for analysis. A literature search of PubMed and Medline for human data using combinations and synonyms of osteoporosis, sarcopenia and obesity, and each mineral and vitamin indicated as insufficient by NHANES. Results: NHANES data suggested phosphorus, calcium, magnesium, potassium, iron, and vitamins B6/B12/C/A/D/E and K were candidates for further evaluation. 170 articles were included. Conclusion: While chronic single/multiple micronutrient insufficiency/excess is not studied in clinical trials, NHANES data suggest that they have existed for at least a decade. Examining the status and roles of those nutrients may be important to understanding the health issues associated with Western-type diets, including development of osteosarcopenic obesity.

As therapeutic uses of high-LET radiation become more prevalent and human space exploration continues to be a focus of NASA, it is important to understand the biological effects of high-LET radiation and the role of genetics in sensitivity to high-LET radiation. To study genetic susceptibility to radiation, we used mice deficient in Atm activity (AtmΔSRI). ATM is important in DNA repair, apoptosis and cell cycle regulation. Although homozygous mutations in ATM are rare, the prevalence of ATM heterozygosity is estimated to be 1% and results in an increased cancer risk. We found that the effects of 1 Gy 1 GeV/nucleon 56Fe particles on life span and tumorigenesis are genotype- and sex-specific. Significant effects of 1 Gy 1 GeV/nucleon 56Fe particles on incidence of non-cancer end points were seen; however, 2 Gy 1 GeV/nucleon 56Fe particles significantly affected neuromotor ability. Our results represent an extensive investigation into the late effects of high-LET radiation exposure in a sex- and ge...

Transgenic mouse models of human cancers represent one of the most promising approaches to elucidate clinically relevant mechanisms of action and provide insights into the treatment efficacy of new antitumor drugs. The use of Trp53 transgenic mice (Trp53 knockout [Trp53(-/-)] mice) for these kinds of studies is, so far, restricted by limitations in detecting developing tumors and the lack of noninvasive tools for monitoring tumor growth, progression, and treatment response.We hypothesized that quantitative small-animal PET with (18)F-FDG was able to detect the onset and location of tumor development, follow tumor progression, and monitor response to chemotherapy. To test these hypotheses, C57BL/6J Trp53(-/-) mice underwent longitudinal small-animal PET during lymphoma development and gemcitabine treatment. Trp53 wild-type (Trp53(+/+)) mice were used as controls, and histology after full necropsy served as the gold standard.In Trp53(+/+) mice, the thymic standardized uptake value (SUV) did not exceed 1.0 g/mL, with decreasing (18)F-FDG uptake over time. Conversely, all Trp53(-/-) mice that developed thymic lymphoma showed increasing thymic glucose metabolism, with a mean SUV doubling time of 9.0 wk (range, 6.0-17.5 wk). Using an SUV of 3.0 g/mL as a criterion provided a sensitivity of 78% and a specificity of 100% for the detection of thymic lymphoma. Treatment monitoring with (18)F-FDG PET correctly identified all histologic responses and relapses to gemcitabine.(18)F-FDG small-animal PET can be used to visualize onset and progression of thymic lymphomas in Trp53(-/-) mice and monitor response to chemotherapy. Thus, (18)F-FDG small-animal PET provides an in vivo means to assess intervention studies in the Trp53 transgenic mouse model.

The 2015 US dietary guidelines advise the importance of good dietary patterns for health, which includes all nutrients. Micronutrients are rarely, if ever, consumed separately, they are not tissue specific in their actions and at the molecular level they are multitaskers. Metabolism functions within a seemingly random cellular milieu however ratios are important, for example, the ratio of adenosine triphosphate to adenosine monophosphate, or oxidized to reduced glutathione. Health status is determined by simple ratios, such as the waist hip ratio, or ratio of fat mass to lean mass. Some nutrient ratios exist and remain controversial such as the omega-6/omega-3 fatty acid ratio and the sodium/potassium ratio. Therefore, examining ratios of micronutrients may convey more information about how diet and health outcomes are related. Summarized micronutrient intake data, from food only, from the National Health and Nutrition Examination Survey, were used to generate initial ratios. Overall, in this preliminary analysis dietary ratios of micronutrients showed some differences between intakes and recommendations. Principles outlined here could be used in nutritional epidemiology and in basic nutritional research, rather than focusing on individual nutrient intakes. This paper presents the concept of micronutrient ratios to encourage change in the way nutrients are regarded.

We determined the prevalence of osteosarcopenic obesity (loss of bone and muscle coexistent with increased adiposity) in overweight/obese postmenopausal women and compared their functionality to obese-only women. Results showed that osteosarcopenic obese women were outperformed by obese-only women in handgrip strength and walking/balance abilities indicating their higher risk for mobility impairments. Osteosarcopenic obesity (OSO) is a recently defined triad of osteopenia/osteoporosis, sarcopenia, and adiposity. We identified women with OSO in overweight/obese postmenopausal women and evaluated their functionality comparing them with obese-only (OB) women. Additionally, women with osteopenic/osteoporotic obesity (OO), but no sarcopenia, and those with sarcopenic obesity (SO), but no osteopenia/osteoporosis, were identified and compared. We hypothesized that OSO women will have the lowest scores for each of the functionality measures. Participants (n = 258; % body fat ≥35) were assessed using a Lunar iDXA instrument for bone and body composition. Sarcopenia was determined from negative residuals of linear regression modeled on appendicular lean mass, height, and body fat, using 20th percentile as a cutoff. Participants with T-scores of L1–L4 vertebrae and/or total femur

The overconsumption of n-6 polyunsaturated fatty acids (PUFA), resulting in a high ratio of n-6 to n-3 PUFA, may contribute to the increased pathogenesis of obesity and osteoporosis by promoting low-grade chronic inflammation (LGCI). As evidence suggests, both obesity and osteoporosis are linked on a cellular and systemic basis. This review will analyze if a relationship exists between LGCI, fat, bone, and n-3 PUFA. During the life cycle, inflammation increases, fat mass accumulates, and bone mass declines, thus suggesting that a connection exists. This review will begin by examining how the current American diet and dietary guidelines may fall short of providing an anti-inflammatory dose of the n-3 PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). It will then define LGCI and outline the evidence for a relationship between fat and bone. Inflammation as it pertains to obesity and osteoporosis and how EPA and DHA can alleviate the associated inflammation will be discussed, followed by some preliminary evidence to show how mesenchymal stem cell (MSC) lineage commitment may be altered by inflammation to favor adipogenesis. Our hypothesis is that n-3 PUFA positively influence obesity and osteoporosis by reducing LGCI, ultimately leading to a beneficial shift in MSC lineage commitment. This hypothesis essentially relates the need for more focused research in several areas such as determining age and lifestyle factors that promote the shift in MSC commitment and if current intakes of EPA and DHA are optimal for fat and bone.

Osteopontin (OPN) is a major noncollagenous protein of bone that is frequently up-regulated in tumors, where it enhances tumor growth. OPN-deficient mice are resistant to stimulated bone resorption, including that occurring after ovariectomy. Using a new syngeneic model of bone metastasis (r3T), we examined whether OPN-deficient mice are similarly resistant to bone loss resulting from osteolytic tumor growth. Transformed mammary epithelial cells, r3T, which express parathyroid hormone-related protein but not receptor activator of nuclear factor-kappaB ligand, were injected via the intracardiac route into both wild-type and OPN-/- mice. We measured tumor burden in the bone by quantitative polymerase chain reaction assay and evaluated bone loss by X-ray and microCT. Unexpectedly, bone loss was similar in OPN-/- and wild-type mice bearing similar-sized tumors. Osteoclast number was comparable in both genotypes, and the expression of bone sialoprotein was similar in tumor-bearing bones of both genotypes, excluding two potential mechanisms of overriding the defect. Taken together, these results indicate that in the absence of OPN, the bone loss associated with tumor growth at the bone site proceeds rapidly despite the osteoclast defects documented in OPN-/- mice, suggesting that the mechanism of bone loss due to tumor growth differs from that occurring in other pathologies.