A step toward precision gerontology: Lifespan effects of calorie and protein restriction are consistent with predicted impacts on entropy generation.

Understanding aging is a key biological goal. Precision gerontology aims to predict how long individuals will live under different treatment scenarios. Calorie and protein restriction (CR and PR) extend lifespan in many species. Using data from C57BL/6 male mice under graded CR or PR, we introduce a computational thermodynamic model for entropy generation, which predicted the impact of the manipulations on lifespan. Daily entropy generation decreased significantly with increasing CR level, but not PR. Our predictions indicated the lifespan of CR mice should increase by 13 to 56% with 10 to 40% CR, relative to ad libitum-fed animals. This prediction was broadly consistent with the empirical observation of the lifespan impacts of CR in rodents. Modeling entropy fluxes may be a future strategy to identify antiaging interventions.

Thermodynamic Assessment of the Effects of Intermittent Fasting and Fatty Liver Disease Diets on Longevity.

Organisms uptake energy from their diet and maintain a highly organized structure by importing energy and exporting entropy. A fraction of the generated entropy is accumulated in their bodies, thus causing ageing. Hayflick's entropic age concept suggests that the lifespan of organisms is determined by the amount of entropy they generate. Organisms die after reaching their lifespan entropy generation limit. On the basis of the lifespan entropy generation concept, this study suggests that an intermittent fasting diet, which means skipping some meals without increasing the calories uptake in the other courses, may increase longevity. More than 1.32 million people died in 2017 because of chronic liver diseases, and a quarter of the world's population has non-alcoholic fatty liver disease. There are no specific dietary guidelines available for the treatment of non-alcoholic fatty liver diseases but shifting to a healthier diet is recommended as the primary treatment. A healthy obese person may generate 119.9 kJ/kg K per year of entropy and generate a total of 4796 kJ/kg K entropy in the first 40 years of life. If obese persons continue to consume the same diet, they may have 94 years of life expectancy. After age 40, Child-Pugh Score A, B, and C NAFLD patients may generate 126.2, 149.9, and 272.5 kJ/kg K year of entropy and have 92, 84, and 64 years of life expectancy, respectively. If they were to make a major recommended shift in their diet, the life expectancy of Child-Pugh Score A, B, and C patients may increase by 29, 32, and 43 years, respectively.

Thermodynamic assessment of allocation of energy and exergy of the nutrients for the life processes during pregnancy.

Thermodynamic analyses are performed to quantify allocation of the nutritional energy and exergy to most of the life processes by pregnant mice. In these analyses, 'internal work performance' is calculated for the first time in the literature for metabolism during pregnancy and found substantially higher than the 'external work performance'. Variation of the daily entropy generation rates and the daily internal work performance rates during the course of pregnancy showed a highly similar phasic behaviour. With the progression of the pregnancy, external work performance decreased and second law efficiency increased significantly. On the 13th day of pregnancy, net energy extracted from the food at the cellular energy metabolism subsystem was 15·0 kJ; approximately 3 kJ of it was employed for daily internal work performance, 0·8 kJ was allocated to daily external work performance and 0·8 kJ was stored in the adipose tissue without entering into the cellular energy metabolism subsystem. Heat generation in association with internal and external work performance was 9·1 and 2·2 kJ, respectively. Energy, pertinent to the first law, and exergy (useful energy), pertinent to the second law, balances are described graphically, and comparison of these plots showed that the total exergy of the nutrients allocated to internal and external work performance and heat generation is substantially smaller in magnitude when compared with those of energy balance.

Assessment of entropy accumulation in human subjects when exposed to low energy availability.

Background & aims: Adequate energy availability is essential for the body to maintain its physiological functions and achieve optimal health, especially among athletes. Unfortunately, low energy availability (LEA) is common among athletes, and it has been associated with impairments in health and performance. In contrast, an energy-restricted diet has been linked to longevity, but it is unclear how LEA affects athletes' lifespans. The goal of the present study was to assess the impact of LEA thermodynamically on the lifespan of athletes. Methods: Data from seven healthy young endurance-trained athletes (24 ± 4 years) who underwent short-term low energy availability (125 (kJ/day) per kg FFM) once with low protein content (LEA-LP; 0.8 g/kg) and with high protein content (LEA-HP; 125 (kJ/day) per kg FFM, 1.7 g/kg), as well as a control diet (CON; 230 (kJ/day) per kg FFM, 1.7 g/kg), were used in the calculations. The athletes followed each diet for five days and expended 67.5 (kJ/day) per kg FFM. entropy generation-based thermodynamic calculations were performed based on the metabolic activity of the athletes, which was determined from oxygen consumption and carbon dioxide production rates. Results: Low energy availability was successfully induced during LEA-LP (62 ± 8 (kJ/day) per kg FFM; 95%Cl: 53-70) and LEA-HP (64 ± 8 (kJ/day) per kg FFM; 95%Cl: 56-71) diets. Despite of achieving energy deficit of -6658 ± 2110 kJ/day (95%Cl: 8609-(-) 4707) (LEA-LP), -5781 ± 623 (95%Cl: 26591-(-)4707) (LEA-HP) and excessive energy of 772 ± 1915 (95%Cl: 845-2388) (CON) statistical analyses revealed no significant differences in lifespan estimations among diets (CON: 72 ± 8 years (95%Cl: 65-79), LEA-LP: 74 ± 7 years (95%Cl: 68-80), and LEA-HP: 73 ± 11 (95%Cl: 62-83)). Conclusions: This study suggests valuable insights into the intricate relationship between energy availability, entropy generation, and lifespan among athletes. Whereas entropy generation levels and the lifespan of athletes remained stable depending on diets, the distinguished differences in energy deficiency and energy availability underline the need for a profounder investigation of underlying physiological mechanisms to improve the health and performance of athletes.

Kinetic assessment of iontophoretic delivery efficiency of niosomal tetracycline hydrochloride incorporated in electroconductive gel.

The purpose of this study was to conduct the kinetic assessment of iontophoretic delivery of niosomal tetracycline-HCl formulated in an electroconductive gel. Tween-80 and Span-80 were used to obtain tetracycline-HCl niosomes with an average diameter of 101.9 ± 3.3 nm, a polydispersity index of 0.247 ± 0.004, a zeta potential of - 34.1 mV, and an entrapment efficiency of 70.08 ± 0.16%. Four different gel preparations, two of which contained niosomal tetracycline-HCl, were transdermally delivered using Franz diffusion cells under the trigger effect of iontophoresis, applied at 0.2, 0.5, and 1 mA/cm2 current density. The control group was the passive diffusion results of the preparation made using a tetracycline-HCl-based drug marketed in Turkey. The control group was compared with the groups that contained (a) tetracycline-HCl in an electroconductive gel, (b) the niosomal tetracycline-HCl formulation in water, and (c) the niosomal tetracycline-HCl formulation in the electroconductive gel. The group with the niosomal formulation in the electroconductive gel displayed the highest increase in iontophoretic transdermal delivery relative to the control group, displaying a 2-, 2.1-, and 2.2-fold increase, respectively, by current density. The experimental results of transdermal delivery using the synergistic effect of niosomal formulation in electroconductive gel and the trigger effect of iontophoresis appeared to divert slightly from zero-order kinetics, demonstrating a statistically significant increase in the rate of controlled transdermal drug delivery. Considering that about 20% of the formulation is transdermally delivered in the first half-hour, the iontophoretic transdermal delivery of niosomal tetracycline-HCl can be efficiently used in local iontophoretic therapy.

Improvement of the safety of the red pepper spice with FMEA and post processing EWMA quality control charts.

Although there are numerous decades-old studies drawing attention to the presence of aflatoxins in spices, and particularly in red pepper spice, the problem has not been eradicated. In the present study, information presented in the literature, about production method of red pepper spice, its contamination with aflatoxin, and the uncertainty about the data are assessed to find out the points where improvement may be achieved. Failure Mode and Effect Analysis (FMEA) are performed to assess the risk. The highest total risk attributable to chemical plus physical plus biological causes is associated with the washing stage (RPN=363), which is followed by the receiving (RPN=342) and the storage (RPN=342) stages. The highest risk attributable to biological causes (RPN=180) is associated with microbial growth and aflatoxin production due to insufficient control of drying conditions. The highest chemical risk (RPN=144) is found for the presence of unintentional food additives, such as pesticides, herbicides, hormones, and heavy metals in fresh red pepper fruits. EWMA (exponentially weighted average) charts are employed to monitor aflatoxin production during storage. They successfully distinguished between the batches, which turned to be unsafe. Risk associated with unintentional additives may be reduced by using certified additives only. Better drying control will definitely reduce the risk associated with the drying process. Codex Alimentarius plan has worldwide acceptance for assessing safety of the nuts. Risk of accepting the batches contaminated with aflatoxin may be eliminated by applying the Codex Alimentarius sampling plan before putting the dry pulverized red pepper into the storage facility.

How does exercise affect energy metabolism? An in silico approach for cardiac muscle.

We explored an in silico model of muscle energy metabolism and demonstrated its theoretical plausibility. Results indicate that energy metabolism triggered by activation can capture the muscle condition, rest, or exercise, and can respond accordingly adjusting the rates of their respiration and energy utilization for efficient use of the nutrients. Our study demonstrated during exercise higher respiratory activity causes a substantial increase in exergy release with an increase in exergy destruction, and entropy generation rate. The thermodynamic analysis showed that at the resting state when the exergy destruction rate was 0.66 W/kg and the respiratory metabolism energetic efficiency was 36% and exergetic efficiency was 32%; whereas, when the exergy destroyed was 1.24 W/kg, the energetic efficiency was 58% and exergetic efficiency was 50% during exercise. The efficiency results suggest the ability of the system to regulate itself in response to higher work demand and become more efficient in terms of converting energy coming from nutrients to useable energy when the circulating medium has sufficient energy precursor.

Diet-dependent entropic assessment of athletes' lifespan.

Life expectancies of the athletes depend on the sports they are doing. The entropic age concept, which was found successful in the previous nutrition studies, will be employed to assess the relation between the athletes' longevity and nutrition. Depending on their caloric needs, diets are designed for each group of athletes based on the most recent guidelines while they are pursuing their careers and for the post-retirement period, and then the metabolic entropy generation was worked out for each group. Their expected lifespans, based on attaining the lifespan entropy limit, were calculated. Thermodynamic assessment appeared to be in agreement with the observations. There may be a significant improvement in the athletes' longevity if they shift to a retirement diet after the age of 50. The expected average longevity for male athletes was 56 years for cyclists, 66 years for weightlifters, 75 years for rugby players and 92 years for golfers. If they should start consuming the retirement diet after 50 years of age, the longevity of the cyclists may increase for 7 years, and those of weightlifters, rugby players and golfers may increase for 22, 30 and 8 years, respectively.

Why women may live longer than men do? A telomere-length regulated and diet-based entropic assessment.

BACKGROUND & AIMS: Empirical analyses of the data available around the word concluded that women have longer life span now, when compared to the men. Available literature unfortunately could not offer full answers to this observation. The "entropic age" concept suggests that ageing related changes in the body, such as loss of molecular functions and overwhelming of the maintenance systems, may be explained in terms of entropy generation. METHODS: Telomere-length regulated entropic assessment based on metabolic activity with four different diets carried out. RESULTS: Estimates of the life expectancy of the women on all of these diets is longer than those of the men. Faster shortening of the telomere lengths in men was the major reason of the shorter life expectancy. The highest and the lowest life expectancy for women were estimated with Mediterranean and the vegetarian diets, respectively; men were estimated to have the longest life span with the vegetarian diet and the shortest life span with the ketogenic diet. CONCLUSIONS: A higher rate of metabolism causes higher entropy generation and hints correlations that can be helpful in future ageing research. Faster shortening of the telomere lengths in men was the major reason of the estimation of the shorter life span for men.

How to Decide on Modeling Details: Risk and Benefit Assessment.

Mathematical models based on thermodynamic, kinetic, heat, and mass transfer analysis are central to this chapter. Microbial growth, death, enzyme inactivation models, and the modeling of material properties, including those pertinent to conduction and convection heating, mass transfer, such as diffusion and convective mass transfer, and thermodynamic properties, such as specific heat, enthalpy, and Gibbs free energy of formation and specific chemical exergy are also needed in this task. The origins, simplifying assumptions, and uses of model equations are discussed in this chapter, together with their benefits. The simplified forms of these models are sometimes referred to as "laws," such as "the first law of thermodynamics" or "Fick's second law." Starting to modeling a study with such "laws" without considering the conditions under which they are valid runs the risk of ending up with erronous conclusions. On the other hand, models started with fundamental concepts and simplified with appropriate considerations may offer explanations for the phenomena which may not be obtained just with measurements or unprocessed experimental data. The discussion presented here is strengthened with case studies and references to the literature.

General Template for the FMEA Applications in Primary Food Processing.

Data on the hazards involved in the primary steps of processing cereals, fruit and vegetables, milk and milk products, meat and meat products, and fats and oils are compiled with a wide-ranging literature survey. After determining the common factors from these data, a general FMEA template is offered, and its use is explained with a case study on pasteurized milk production.

Formation and stabilization of nanoemulsion-based vitamin E delivery systems using natural biopolymers: Whey protein isolate and gum arabic.

Natural biopolymers, whey protein isolate (WPI) and gum arabic (GA), were used to fabricate emulsion-based delivery systems for vitamin E-acetate. Stable delivery systems could be formed when vitamin E-acetate was mixed with sufficient orange oil prior to high pressure homogenization. WPI (d32=0.11 µm, 1% emulsifier) was better than GA (d32=0.38 µm, 10% emulsifier) at producing small droplets at low emulsifier concentrations. However, WPI-stabilized nanoemulsions were unstable to flocculation near the protein isoelectric point (pH 5.0), at high ionic strength (>100mM), and at elevated temperatures (>60 °C), whereas GA-stabilized emulsions were stable. This difference was attributed to differences in emulsifier stabilization mechanisms: WPI by electrostatic repulsion; GA by steric repulsion. These results provide useful information about the emulsifying and stabilizing capacities of natural biopolymers for forming food-grade vitamin-enriched delivery systems.

Nanoemulsion delivery systems for oil-soluble vitamins: Influence of carrier oil type on lipid digestion and vitamin D3 bioaccessibility.

The influence of carrier oil type on the bioaccessibility of vitamin D3 encapsulated within oil-in-water nanoemulsions prepared using a natural surfactant (quillaja saponin) was studied using a simulated gastrointestinal tract (GIT) model: mouth; stomach; small intestine. The rate of free fatty acid release during lipid digestion decreased in the following order: medium chain triglycerides (MCT) > corn oil ≈ fish oil > orange oil > mineral oil. Conversely, the measured bioaccessibility of vitamin D3 decreased in the following order: corn oil ≈ fish oil > orange oil > mineral oil > MCT. These results show that carrier oil type has a considerable impact on lipid digestion and vitamin bioaccessibility, which was attributed to differences in the release of bioactives from lipid droplets, and their solubilization in mixed micelles. Nanoemulsions prepared using long chain triglycerides (corn or fish oil) were most effective at increasing vitamin bioaccessibility.

Astrocyte-neuron lactate shuttle may boost more ATP supply to the neuron under hypoxic conditions--in silico study supported by in vitro expression data.

BACKGROUND: Neuro-glial interactions are important for normal functioning of the brain as well as brain energy metabolism. There are two major working models--in the classical view, both neurons and astrocytes can utilize glucose as the energy source through oxidative metabolism, whereas in the astrocyte-neuron lactate shuttle hypothesis (ANLSH) it is the astrocyte which can consume glucose through anaerobic glycolysis to pyruvate and then to lactate, and this lactate is secreted to the extracellular space to be taken up by the neuron for further oxidative degradation. RESULTS: In this computational study, we have included hypoxia-induced genetic regulation of these enzymes and transporters, and analyzed whether the ANLSH model can provide an advantage to either cell type in terms of supplying the energy demand. We have based this module on our own experimental analysis of hypoxia-dependent regulation of transcription of key metabolic enzymes. Using this experimentation-supported in silico modeling, we show that under both normoxic and hypoxic conditions in a given time period ANLSH model does indeed provide the neuron with more ATP than in the classical view. CONCLUSIONS: Although the ANLSH is energetically more favorable for the neuron, it is not the case for the astrocyte in the long term. Considering the fact that astrocytes are more resilient to hypoxia, we would propose that there is likely a switch between the two models, based on the energy demand of the neuron, so as to maintain the survival of the neuron under hypoxic or glucose-and-oxygen-deprived conditions.