Energetic cost of biosynthesis is a missing link between growth and longevity in mammals.

The comparative studies of aging have established a negative correlation between Gompertz postnatal growth constant and maximum lifespan across mammalian species, but the underlying physiological mechanism remains unclear. This study shows that the Gompertz growth constant can be decomposed into two energetic components, mass-specific metabolic rate and the energetic cost of biosynthesis, and that after controlling the former as a confounder, the negative correlation between growth constant and lifespan still exists due to a 100-fold variation in the latter, revealing that the energetic cost of biosynthesis is a link between growth and longevity in mammals. Previously, the energetic cost of biosynthesis has been thought to be a constant across species and therefore was not considered a contributor to the variation in any life history traits, such as growth and lifespan. This study employs a recently proposed model based on energy conservation to explain the physiological effect of the variation in this energetic cost on the aging process and illustrates its role in linking growth and lifespan. The conventional life history theory suggested a tradeoff between growth and somatic maintenance, but the findings in this study suggest that allocating more energy to biosynthesis may enhance the somatic maintenance and extend lifespan and, hence, reveal a more complex nature of the tradeoff.

Comparison of Energy Budget of Cockroach Nymph (Hemimetabolous) and Hornworm (Holometabolous) under Food Restriction.

Animals with different life histories budget their intake energy differently when food availability is low. It has been shown previously that hornworm (larva of Manduca sexta), a holometabolous insect species with a short development stage, prioritizes growth at the price of metabolism under food restriction, but it is unclear how hemimetabolous insect species with a relatively long development period budget their intake energy under food scarcity. Here, we use orange head cockroaches (Eublaberus posticus) to investigate this question. We found that for both species under food restriction, rates of metabolism and growth were suppressed, but the degree of reduction was more severe in growth than that of metabolism for cockroaches. Under both free-feeding and food restriction conditions, hornworms allocated a larger fraction of assimilated energy to growth than to metabolism, and cockroaches were the opposite. More importantly, when food availability was low, the fraction of assimilated energy allocated to growth was reduced by 120% in cockroaches, and the energy from growth was channeled to compensate for the reduction in metabolism; but, the fraction of assimilated energy allocated to growth was only reduced by 14% in hornworms. These results suggest that, compared to hornworms, cockroaches prioritize metabolism over growth.

Link between Energy Investment in Biosynthesis and Proteostasis: Testing the Cost-Quality Hypothesis in Insects.

The energy requirement for biosynthesis plays an important role in an organism's life history, as it determines growth rate, and tradeoffs with the investment in somatic maintenance. This energetic trait is different between painted lady (Vanessa cardui) and Turkestan cockroach (Blatta lateralis) due to the different life histories. Butterfly caterpillars (holometabolous) grow 30-fold faster, and the energy cost of biosynthesis is 20 times cheaper, compared to cockroach nymphs (hemimetabolous). We hypothesize that physiologically the difference in the energy cost is partially attributed to the differences in protein retention and turnover rate: Species with higher energy cost may have a lower tolerance to errors in newly synthesized protein. Newly synthesized proteins with errors are quickly unfolded and refolded, and/or degraded and resynthesized via the proteasomal system. Thus, much protein output may be given over to replacement of the degraded new proteins, so the overall energy cost on biosynthesis is high. Consequently, the species with a higher energy cost for biosyntheses has better proteostasis and cellular resistance to stress. Our study found that, compared to painted lady caterpillars, the midgut tissue of cockroach nymphs has better cellular viability under oxidative stresses, higher activities of proteasome 20S, and a higher RNA/growth ratio, supporting our hypothesis. This comparative study offers a departure point for better understanding life history tradeoffs between somatic maintenance and biosynthesis.

Safety assessment of oil extracted from lacquer (Toxicodendron vernicifluum (Stokes) F.A. Barkley) seed: acute and subchronic toxicity studies in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Toxicodendron vernicifluum (Stokes) F.A. Barkley (RVS) is an economic tree species and widely distributed in East Asia. Wood parts and raw lacquers of RVS have been used in coatings, herbal medicines or food supplements, and the leaves, flowers, roots, and fruits of RVS are also widely used in medicine traditionally. Lacquer seed oil (LSO) has potential health benefits and has not previously been evaluated for safety. AIM OF THE STUDY: The aim of the present study was to investigate the toxicological potential of LSO by acute and subchronic toxicity tests. MATERIALS AND METHODS: The characterization of fatty acids of the LSO was carried out by gas chromatography. In the acute toxicity study, LSO was administered at single doses of 5000 or 10000 mg/kg by oral gavage. The subchronic toxicity study was conducted by daily oral administration of LSO at doses of 1250, 2500 and 5000 mg/kg/day for 30 consecutive days. The animals were evaluated for clinical observations, body weight, organ weight, feed consumption, biochemical and hematological parameters, and liver, lung, and kidney histology. RESULTS: There were no mortality and toxic changes were observed in acute toxicity study. The results of subchronic toxicity showed no toxicologically significant changes in clinical observations, body weight, organ weight, biochemical or hematological parameters. Histopathologic results indicated slight hepatic steatosis and inflammatory infiltration in the rats of 5000 mg/kg/day LSO treated group. However, the histopathologic observation was not confirmed by hepatic biochemical analysis. CONCLUSIONS: These results suggested that the LD50 of LSO is over 10000 mg/kg and LSO is non-toxic for SD rats in acute toxicity study. The no observed adverse effect level (NOAEL) of LSO in rats is considered to be 5000 mg/kg/day, and liver is the potential target organ of LSO for 30-day subchronic toxicity study.

Quantitative Assessment of Finger Movement Profile in a Visual-Motor Task Based on a Tablet Computer: The Application in Parkinson's Disease.

BACKGROUND/OBJECTIVE: Easily applicable, quantitative assessment of movement is widely needed in various clinical settings, especially in the evaluation of Parkinson's disease (PD). METHODS: We developed a highly repeatable tablet computer-based finger movement assessment system (FMAS) to record finger movement profile in a visual-motor task both in PD (n = 217) and healthy participants (n = 221). RESULTS: We found age-related declines in finger movement performance among the healthy participants but not in PD patients with the FMAS. Significant differences in movement time (MT) and latency/MT ratio but not in latency were observed in PD patients as compared with healthy subjects (P < 0.000). Meanwhile, we identified the latency/MT ratio as the optimal parameter to differentiate PD from age-matched healthy subjects in an age-independent manner (cut-off 1.08 with corresponding AUC = 0.861). In addition, a significant correlation was found between finger movement parameters and the Hoehn and Yahr scale (H-Y scale), UPDRS III score and the duration of the disease in PD patients (P < 0.01). CONCLUSION: It was suggested that the tablet computer-based evaluation of finger movement provided an easily applicable quantitative method to assess the conditions of PD patients.

Transurethral resection of the prostate achieves favorable outcomes in stroke patients with symptomatic benign prostate hyperplasia.

OBJECTIVES: To evaluate the surgical outcomes of stroke patients with symptomatic benign prostatic hyperplasia (BPH) who underwent transurethral resection of the prostate (TURP) and compare the clinical outcomes between patients with stroke and those without stroke receiving this procedure. METHODS: This retrospective cohort study analyzed claims data collected during the period of 1997-2012 from Taiwan National Health Insurance Research Database. We enrolled 6625 patients who had persistent lower urinary tract symptoms and underwent TURP for BPH. They were categorized into a stroke (n = 577) and nonstroke (n = 6048) group. Patient characteristics, postoperative clinical outcomes, medication records, and medical expenses were compared. RESULTS: Compared with the stroke group patients, those in the nonstroke group were younger, had fewer comorbidities, and more favorable postoperative clinical outcomes. Nevertheless, TURP achieved favorable outcomes in stroke patients with symptomatic BPH. In the stroke group, the rate of urinary tract infection (UTI) decreased from 34.7% during 1 year preoperatively to 29.8% during 1 year postoperatively (p = .05). The rate of urinary retention (UR) also decreased from 55.5% during 1 year preoperatively to 22.5% during 1 year postoperatively (p = .05). TURP reduced the overall medical expenses of patients with stroke. Annual patient medical expense during 1 year preoperatively, 1 year postoperatively, 2 years postoperatively, and 3 years postoperatively was NT$659,000, NT$646,000, NT$560,000, and NT$599,000, respectively. CONCLUSIONS: In patients with stroke, TURP reduces the risks of UTI and UR and annual total medical expense.

Is diabetes mellitus associated with clinical outcomes in aging males treated with transurethral resection of prostate for bladder outlet obstruction: implications from Taiwan Nationwide Population-Based Cohort Study.

PURPOSE: We assessed the lower urinary tract symptoms (LUTSs) and clinical outcomes between diabetes mellitus (DM) patients and non-diabetic (non-DM) patients receiving transurethral resection of prostate (TUR-P). METHODS: This analysis was a retrospective cohort study using 13 years (2000-2012) of claims data from Taiwan's National Health Insurance Research Database (NHIRD). A total of 4,887 patients who had persistent LUTSs and underwent TUR-P for prostate enlargement (benign prostate enlargement [BPE]) were enrolled and divided into two groups: DM and non-DM groups. The patients' characteristics, postoperative clinical outcomes, and the medication records after TUR-P were compared. Chi-square test was used for categorical variables and independent samples t-test for continuous variables. Multivariable logistic regression analysis was used to compare the risk of postoperative outcomes. Finally, we estimated the medication-free survival rate after TUR-P using Kaplan-Meier method and compared it between study groups using log-rank test. RESULTS: DM group patients had a higher prevalence of comorbidities. Postoperatively, the DM group had lower rates of urinary tract infection (UTI; odds ratio [OR], 0.78; P=0.009) and higher rates of urinary retention requiring catheterization (OR, 1.35; P=0.01) within 1 month after TUR-P. A higher proportion of patients with DM took anti-muscarinics (OR, 1.23; P=0.032) within the first 3 months and α-blockers (OR, 1.18; P=0.049) during 3-12 months after receiving TUR-P. Overall, the DM group patients had a worse postoperative medication-free survival compared to that of non-DM group patients (95% confidence interval [95% CI], 1.14; P=0.005). CONCLUSION: DM patients require higher rates of continuing medication after TUR-P, especially anti-muscarinics in 3 months postoperatively and alpha-blocker after 3 months postoperatively. DM patients also had higher incidence of urine retention after surgery. DM patients had relatively poor treatment outcomes compared to DM-free patients.

Economic Evaluation Study (Cheer Compliant) Laser Prostatectomy for Benign Prostatic Hyperplasia: Outcomes and Cost-effectiveness.

To determine which surgical treatment for lower urinary tract symptoms, which is suggestive of benign prostatic hyperplasia (BPH), is more cost-effective and yields a better patient's preference. Treatment outcome, cost, and perioperative complications to assess the treatment effectiveness of using laser prostatectomy as a treatment for BPH were investigated in this study.This retrospective study included 100 patients who underwent transurethral resection of prostate (TUR-P) and another 100 patients who received high-powered 120 W (GreenLight HPS) laser prostatectomy between 2005 and 2011.International Prostate Symptom Score and uroflow parameters were collected before the surgery and the uroflow and postvoiding residual volumes were evaluated before treatment and at 3, 6, 12, and 24 months after treatment. The results of 100 treatments after HPS laser prostatectomy were compared with the results of 100 patients who received TUR-P from the same surgeon. Complication rates and admission costs were analyzed.From 2005 to 2011, 200 consecutive patients underwent endoscopic surgery. Study participants were men with BPH with mean age of 71.3 years old. The peak flow rate went from 8.47 to 15.83 mL/s for 3 months after laser prostatectomy. Laser therapy groups showed better improvement in symptom score, shortened length of stay, and quality of life score when compared with those of TUR-P procedures. The estimated cost for laser prostatectomy was high when compared with cost of any other TUR-P procedural option at Chang Gung Hospital (P = 0.001). All admission charges were similar except for the cost of the laser equipment and accessories (mainly the laser fiber) (P = 0.001). Due to this cost of equipment, it increased the total admission charges for the laser group and therefore made the cost for the laser group higher than that of the TUR-P group.Perioperative complications, such as the need for checking for bleeding, urinary retention rate or urosepsis rate within 30 days after the surgery, held no significant differences between both groups.Compared with alternative treatment options, laser prostatectomy of the prostate is clinically effective but yields a high cost of treatment for symptomatic BPH.

On the complex relationship between energy expenditure and longevity: Reconciling the contradictory empirical results with a simple theoretical model.

The relationship between energy expenditure and longevity has been a central theme in aging studies. Empirical studies have yielded controversial results, which cannot be reconciled by existing theories. In this paper, we present a simple theoretical model based on first principles of energy conservation and allometric scaling laws. The model takes into considerations the energy tradeoffs between life history traits and the efficiency of the energy utilization, and offers quantitative and qualitative explanations for a set of seemingly contradictory empirical results. We show that oxidative metabolism can affect cellular damage and longevity in different ways in animals with different life histories and under different experimental conditions. Qualitative data and the linearity between energy expenditure, cellular damage, and lifespan assumed in previous studies are not sufficient to understand the complexity of the relationships. Our model provides a theoretical framework for quantitative analyses and predictions. The model is supported by a variety of empirical studies, including studies on the cellular damage profile during ontogeny; the intra- and inter-specific correlations between body mass, metabolic rate, and lifespan; and the effects on lifespan of (1) diet restriction and genetic modification of growth hormone, (2) the cold and exercise stresses, and (3) manipulations of antioxidant.

Increasing energetic cost of biosynthesis during growth makes refeeding deleterious.

Diet restriction (DR) enhances animals' health maintenance, but refeeding reverses its beneficial effects. However, to what degree refeeding reverses the beneficial effects of DR remains controversial. Here, I develop a theoretical model for reconciling the results of refeeding studies and understanding the dynamic and reversible mechanism underlying the effects of diet on health from the energetic viewpoint. By illustrating the negative correlation between health maintenance and the energetic cost of growth in animals under different diet regimes, the model explains why, in some cases, refed animals have better health and live longer than freely fed controls. More importantly, the model reveals that, in some species, the energetic cost of synthesizing biomass increases during growth, so the expensive compensatory growth induced by refeeding later in life offsets the benefits of the inexpensive retarded growth induced by diet restriction early in life. Thus, in these species, refeeding drives animals to allocate more energy to growth and less to maintenance and therefore leads to poor health status and shorter life span compared to freely fed controls.