Senolytic-Resistant Senescent Cells Have a Distinct SASP Profile and Functional Impact: The Path to Developing Senosensitizers.

The senescent cell (SC) fate is linked to aging, multiple disorders and diseases, and physical dysfunction. Senolytics, agents that selectively eliminate 30-70% of SCs, act by transiently disabling the senescent cell anti-apoptotic pathways (SCAPs), which defend those SCs that are pro-apoptotic and pro-inflammatory from their own senescence-associated secretory phenotype (SASP). Consistent with this, a JAK/STAT inhibitor, Ruxolitinib, which attenuates the pro-inflammatory SASP of senescent human preadipocytes, caused them to become "senolytic-resistant".

Associations among Human Milk Polyunsaturated Fatty Acids and Infant Sleep Patterns: A Cross-Sectional Study.

Background: Infant sleep is critical for cognitive, emotional, and long-term health outcomes. Although diet-sleep relationships are established, limited research has explored how polyunsaturated fatty acids (PUFAs) in human milk (HM) relate to infant sleep.

Objectives: This study aims to examine associations between PUFAs in HM and sleep patterns in 2-mo-old infants exclusively fed with HM.

"Shaking the ladder" reveals how analytic choices can influence associations in nutrition epidemiology: beef intake and coronary heart disease as a case study.

Nutrition epidemiological models involve many analytic decisions, such as defining exposures, selecting which covariates to include, or configuring variables in different ways. We explored the impact of analytical decisions on conclusions in nutrition epidemiology using self-reported beef intake and incident coronary heart disease as a case study. We used REasons for Geographic and Racial Differences in Stroke (REGARDS) data, and selected covariates and their configurations from published literature to recapitulate common models used to assess associations between meat intake and health outcomes.

Food noise: definition, measurement, and future research directions.

The term food noise has been recently popularized by individuals managing their weight or adhering to specific diets for health reasons. Anecdotal evidence from patients and clinical observations suggests that food noise involves constant preoccupation with food-related decisions-such as which foods to eat, caloric intake, macronutrient balance, and meal timing-which can become intrusive and unpleasant. Food noise also appears to affect cognitive burden and quality of life, and is being cited as one reason weight-loss attempts fail.

Effectiveness of a digital weight management program on diet quality: a randomized controlled trial.

Background: The effect of behavioral commercial weight programs (CP) on weight loss is clear, yet their effects on diet quality are less studied.

Objectives: This study aims to evaluate the relative effectiveness of a digital CP on diet quality compared with standard nutritional guidance (SNG) over 6 months.

Methods: This randomized controlled trial (clinicaltrials.

Adjusting for covariates representing potential confounders, mediators, or competing predictors in the presence of measurement error: Dispelling a potential misapprehension and insights for optimal study design with nutritional epidemiology examples.

Background: Variables such as dietary intake are measured with error yet frequently used in observational epidemiology. Although this limitation is sometimes noted, these variables are still often modeled as covariates without formal correction or sincere dialogue about measurement unreliability potentially weakening the validity of statistical conclusions. Further, larger sample sizes increase power (bias) to detect spurious correlations.

"Non-Markovian" and "directional" errors inhibit scientific self-correction and can lead fields of study astray: an illustration using gardening and obesity-related outcomes.

Herein we coin the terms non-Markovian error and biased Markovian error to describe categories of scientific errors for which general progress within a field of study may be unlikely to result in scientific self-correction. We provide examples of such errors and show their impact on studies about gardening and obesity.

The harms of high protein intake: conjectured, postulated, claimed, and presumed, but shown?

High-protein (HP) diets and protein-supplemented foods and beverages have become increasingly popular in adults due to potential benefits relating to appetite, energy intake, body weight, and body composition, and questions have been posed regarding whether current dietary recommendations for protein are too low. At the same time, health concerns relating to high-protein diets have been widespread in the literature for >60 y. However, the conjectured harms of HP diets, which remain prevalent in the lay and sometimes academic literature, are often without strong scientific evidence or may actually be contradicted to a reasonable degree of certainty by scientific evidence.

Fecal glucocorticoid metabolite and T3 profiles of orphaned elephants differ from non-orphaned elephants in Zambia.

Background: Elephants provide valuable insight into how early-life adverse events (ELAEs) associate with animal health and welfare because they can live to advanced ages, display extensive cognitive and memory capabilities, and rely heavily on social bonds. Although it is known that African savanna elephants that experienced ELAEs, such as being orphaned due to human activities, have altered behavioral outcomes, little is known regarding the physiological consequences associated with those stressors.

Methods: We compared fecal glucocorticoid (fGCM) and thyroid (fT3) metabolites as well as body condition scores (BCS) in rescued and rehabilitated orphaned (early-dry season:  = 20; late-dry season:  = 21 elephants) African savanna elephants in Kafue National Park, Zambia to age- and sex-matched wild non-orphaned controls groups (early-dry season:  = 57; late-dry season:  = 22 elephants) during the early- (May/June) and late- (September/October) dry seasons, respectively.

Improving Statistical Rigor in Animal Aging Research by Addressing Clustering and Nesting Effects: Illustration with the National Institute on Aging's Intervention Testing Program Data.

Clustering effects, such as those introduced by housing animals in shared cages, are often overlooked in preclinical lifespan studies, despite their potential to distort variance estimates and inflate Type I error rates, leading to misleading conclusions. This methodological oversight reduces statistical rigor and may undermine the reliability of findings. To address this gap, the current study examines the impact of accounting for clustering and nesting effects on lifespan analyses by comparing the results of statistical models which both account for and ignore these effects.

The misalignment of incentives in academic publishing and implications for journal reform.

For most researchers, academic publishing serves two goals that are often misaligned-knowledge dissemination and establishing scientific credentials. While both goals can encourage research with significant depth and scope, the latter can also pressure scholars to maximize publication metrics. Commercial publishing companies have capitalized on the centrality of publishing to the scientific enterprises of knowledge dissemination and academic recognition to extract large profits from academia by leveraging unpaid services from reviewers, creating financial barriers to research dissemination, and imposing substantial fees for open access.

Evaluating the Reproducibility and Verifiability of Nutrition Research: A Case Study of Studies Assessing the Relationship Between Potatoes and Colorectal Cancer.

Background: The credibility of nutritional research is dependent on the rigor with which studies are conducted and the ability for independent assessment to be performed. Despite the importance of these, more work is needed in the field of nutrition to buttress the trustworthiness of nutrition research.

Objective: To develop and apply a process for evaluating the rigor, reproducibility, and verifiability of nutritional research, using the relationship between potato consumption and Colorectal cancer (CRC) as a case study.

A hematology-based clock derived from the Study of Longitudinal Aging in Mice to estimate biological age.

Biological clocks and other molecular biomarkers of aging are difficult to implement widely in a clinical setting. In this study, we used routinely collected hematological markers to develop an aging clock to predict blood age and determine whether the difference between predicted age and chronologic age (aging gap) is associated with advanced aging in mice. Data from 2,562 mice of both sexes and three strains were drawn from two longitudinal studies of aging.

Hidden: A Baker's Dozen Ways in Which Research Reporting is Less Transparent than it Could be and Suggestions for Implementing Einstein's Dictum.

The tutelage of our mentors as scientists included the analogy that writing a good scientific paper was an exercise in storytelling that omitted unessential details that did not move the story forward or that detracted from the overall message. However, the advice to not get lost in the details had an important flaw. In science, it is the many details of the data themselves and the methods used to generate and analyze them that give conclusions their probative meaning.

Reproduction has immediate effects on female mortality, but no discernible lasting physiological impacts: A test of the disposable soma theory.

The disposable soma theory (DST) posits that organisms age and die because of a direct trade-off in resource allocation between reproduction and somatic maintenance. DST predicts that investments in reproduction accentuate somatic damage which increase senescence and shortens lifespan. Here, we directly tested DST predictions in breeding and nonbreeding female C57BL/6J mice.

Mapping epidermal and dermal cellular senescence in human skin aging.

Single-cell RNA sequencing and spatial transcriptomics enable unprecedented insight into cellular and molecular pathways implicated in human skin aging and regeneration. Senescent cells are individual cells that are irreversibly cell cycle arrested and can accumulate across the human lifespan due to cell-intrinsic and -extrinsic stressors. With an atlas of single-cell RNA-sequencing and spatial transcriptomics, epidermal and dermal senescence and its effects were investigated, with a focus on melanocytes and fibroblasts.

On the pathogenesis of obesity: causal models and missing pieces of the puzzle.

Application of the physical laws of energy and mass conservation at the whole-body level is not necessarily informative about causal mechanisms of weight gain and the development of obesity. The energy balance model (EBM) and the carbohydrate-insulin model (CIM) are two plausible theories, among several others, attempting to explain why obesity develops within an overall common physiological framework of regulation of human energy metabolism. These models have been used to explain the pathogenesis of obesity in individuals as well as the dramatic increases in the prevalence of obesity worldwide over the past half century.

Fetal sex effects on maternal health can now be tested via randomization: A first-in-class illustration in cows on glucoregulatory outcomes.

Background: The maternal-offspring relationship, such as whether fetal sex influences maternal health, is essential to explore to advance prenatal and maternal health. While associations exist between fetal sex and maternal health outcomes, it is unclear whether these reflect a causal relationship.

Objective: To demonstrate that fetal sex can be randomly assigned to test the causal effect of fetal sex on maternal outcomes.

Assessing the state of obesity care: Quality, access, guidelines, and standards.

Background: An international panel of obesity medicine experts from multiple professional organizations examined patterns of obesity care and current obesity treatment guidelines to identify areas requiring updating in response to emerging science and clinical evidence.

Aims: The panel focused on multiple medical health and societal issues influencing effective treatment of obesity and identified several unmet needs in the definition, assessment, and care of obesity.

Methods: The panel was held in Leesburg, Virginia in September 2019.

Guilt by association: Plant-based foods can be incorporated into both healthy and unhealthy plant-based diet indices associated with coronary heart disease.

Background: One approach to test for differential associations between plant foods with health uses a scoring approach: foods categorized into animal or 'healthy' plant-based or 'unhealthy' plant-based groups to construct a plant-based diet index (PDI), healthy PDI (hPDI), and unhealthy PDI (uPDI).

Objective: To evaluate robustness of associations between diet indices and incident coronary heart disease (CHD) risk when recategorizing food groups in indices.

Methods: Using REasons for Geographic and Racial Differences in Stroke (REGARDS) data, we replicated a published use of the scoring approach.

A Bayesian semi-parametric scalar-on-function regression with measurement error using instrumental variables.

Wearable devices such as the ActiGraph are now commonly used in research to monitor or track physical activity. This trend corresponds with the growing need to assess the relationships between physical activity and health outcomes, such as obesity, accurately. Device-based physical activity measures are best treated as functions when assessing their associations with scalar-valued outcomes such as body mass index.

Benefits of calorie restriction in mice are mediated via energy imbalance, not absolute energy or protein intake.

Caloric restriction (CR) results in reduced energy and protein intake, raising questions about protein restriction's contribution to CR longevity benefits. We kept ad libitum (AL)-fed male C57BL/6J mice at 27°C (AL27) and pair-fed (PF) mice at 22°C (22(PF27)). The 22(PF27) group was fed to match AL27 while restricted for calories due to cold-induced metabolism.

Catalyzing communities of research rigour champions.

The biomedical sciences must maintain and enhance a research culture that prioritizes rigour and transparency. The US National Institute of Neurological Disorders and Stroke convened a workshop entitled 'Catalyzing Communities of Research Rigor Champions' that brought together a diverse group of leaders in promoting research rigour and transparency (identified as 'rigour champions') to discuss strategies, barriers and resources for catalyzing technical, cultural and educational changes in the biomedical sciences. This article summarizes 2 days of panels and discussions and provides an overview of critical barriers to research rigour, perspectives behind reform initiatives and considerations for stakeholders across science.