Tsukasa Yoshida

Total daily energy expenditure ("total expenditure") reflects daily energy needs and is a critical variable in human health and physiology, but its trajectory over the life course is poorly studied. We analyzed a large, diverse database of total expenditure measured by the doubly labeled water method for males and females aged 8 days to 95 years. Total expenditure increased with fat-free mass in a power-law manner, with four distinct life stages. Fat-free mass-adjusted expenditure accelerates rapidly in neonates to ~50% above adult values at ~1 year; declines slowly to adult levels by ~20 years; remains stable in adulthood (20 to 60 years), even during pregnancy; then declines in older adults. These changes shed light on human development and aging and should help shape nutrition and health strategies across the life span.

BACKGROUND: It is well known that loss of muscle mass (quantitative change) is a major change that occurs with aging. Qualitative changes in skeletal muscle, such as increased intramuscular fat, also occur as one ages. Enhanced echo intensity (EI) on ultrasonography images of skeletal muscle is believed to reflect muscle quality. Recent studies evaluating the quality of skeletal muscle using computer-aided gray scale analysis showed that EI is associated with muscle strength independently of age or muscle size in middle-aged and elderly women. The aim of the present study was to investigate whether muscle quality based on EI is associated with muscle strength independently of muscle size for elderly men. METHODS: A total of 184 elderly men (65-91 years) living independently in Kyoto, Japan, participated in this study. The EI, muscle thickness (MT), and subcutaneous fat thickness (FT) of the anterior compartment of the right thigh were determined by assessing ultrasonography images. The maximum isometric torque of knee extension at a knee angle of 90° was measured. RESULTS: The EI showed a significant negative correlation with muscle strength (r = -0.333, P < 0.001). Multivariate regression analysis revealed that the MT and EI of the knee extensor muscle were independently associated with maximum isometric knee extension strength. Even when partial correlation analysis was performed with age, height, weight, and FT as control variables, EI was still significantly correlated with muscle strength. CONCLUSION: The results of this study indicate that aging-related changes in muscle quality contribute to diminishing muscle strength. Ultrasonography is a low-cost, easily accessible, and safe method suitable for the assessment of EI as an index of muscle quality.

Abstract Purpose: Patients with pancreatic neuroendocrine neoplasm grade-3 (PanNEN-G3) show variable responses to platinum-based chemotherapy. Recent studies indicated that PanNEN-G3 includes well-differentiated neuroendocrine tumor with G3 (NET-G3). Here, we examined the clinicopathologic and molecular features of PanNEN-G3 and assessed the responsiveness to chemotherapy and survival. Experimental Design: A total of 100 patients with PanNEN-G3 were collected from 31 institutions, and after central review characteristics of each histologic subtype [NET-G3 vs. pancreatic neuroendocrine carcinoma (NEC-G3)] were analyzed, including clinical, radiological, and molecular features. Factors that correlate with response to chemotherapy and survival were assessed. Results: Seventy patients analyzed included 21 NETs-G3 (30%) and 49 NECs-G3 (70%). NET-G3 showed lower Ki67-labeling index (LI; median 28.5%), no abnormal Rb expression (0%), and no mutated KRAS (0%), whereas NEC-G3 showed higher Ki67-LI (median 80.0%), Rb loss (54.5%), and KRAS mutations (48.7%). Chemotherapy response rate (RR), platinum-based chemotherapy RR, and prognosis differed significantly between NET-G3 and NEC-G3. Chemotherapeutic outcomes were worse in NET-G3 (P &amp;lt; 0.001). When we stratified PanNEN-G3 with Rb and KRAS, PanNENs-G3 with Rb loss and those with mutated KRAS showed significantly higher RRs to platinum-based chemotherapy than those without (Rb loss, 80% vs. normal Rb, 24%, P = 0.006; mutated KRAS, 77% versus wild type, 23%, P = 0.023). Rb was a predictive marker of response to platinum-based chemotherapy even in NEC-G3 (P = 0.035). Conclusions: NET-G3 and NEC-G3 showed distinct clinicopathologic characteristics. Notably, NET-G3 does not respond to platinum-based chemotherapy. Rb and KRAS are promising predictors of response to platinum-based chemotherapy for PanNEN-G3, and Rb for NEC-G3. Clin Cancer Res; 23(16); 4625–32. ©2017 AACR.

over this size range that agrees well with indirect calorimetry (average difference 0.64%; SD = 12.2%). We propose adoption of these equations in future studies.

Understanding the impacts of activity on energy balance is crucial. Increasing levels of activity may bring diminishing returns in energy expenditure because of compensatory responses in non-activity energy expenditures.1Pontzer H. Durazo-Arvizu R. Dugas L.R. Plange-Rhule J. Bovet P. Forrester T.E. Lambert E.V. Cooper R.S. Schoeller D.A. Luke A. Constrained total energy expenditure and metabolic adaptation to physical activity in adult humans.Curr. Biol. 2016; 26: 410-417Abstract Full Text Full Text PDF PubMed Scopus (145) Google Scholar, 2Halsey L.G. The mystery of energy compensation.arXiv. 2021; (arXiv:2107.13418)https://arxiv.org/abs/2107.13418Google Scholar, 3Halsey L.G. Green J.A. Twiss S.D. Arnold W. Burthe S.J. Butler P.J. Cooke S.J. Grémillet D. Ruf T. Hicks O. Flexibility, variability and constraint in energy management patterns across vertebrate taxa revealed by long-term heart rate measurements.Funct. Ecol. 2019; 33: 260-272Crossref Scopus (23) Google Scholar This suggestion has profound implications for both the evolution of metabolism and human health. It implies that a long-term increase in activity does not directly translate into an increase in total energy expenditure (TEE) because other components of TEE may decrease in response—energy compensation. We used the largest dataset compiled on adult TEE and basal energy expenditure (BEE) (n = 1,754) of people living normal lives to find that energy compensation by a typical human averages 28% due to reduced BEE; this suggests that only 72% of the extra calories we burn from additional activity translates into extra calories burned that day. Moreover, the degree of energy compensation varied considerably between people of different body compositions. This association between compensation and adiposity could be due to among-individual differences in compensation: people who compensate more may be more likely to accumulate body fat. Alternatively, the process might occur within individuals: as we get fatter, our body might compensate more strongly for the calories burned during activity, making losing fat progressively more difficult. Determining the causality of the relationship between energy compensation and adiposity will be key to improving public health strategies regarding obesity.