Resilience: Biological Basis and Clinical Significance - A Perspective Report from the International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force.

The Resilience is a construct receiving growing attention from the scientific community in geriatrics and gerontology. Older adults show extremely heterogeneous (and often unpredictable) responses to stressors. Such heterogeneity can (at least partly) be explained by differences in resilience (i.e., the capacity of the organism to cope with stressors). The International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force met in Boston (MA,USA) on April 20, 2022 to discuss the biological and clinical significance of resilience in older adults. The identification of persons with low resilience and the prompt intervention in this at-risk population may be critical to develop and implement preventive strategies against adverse events. Unfortunately, to date, it is still challenging to capture resilience, especially due to its dynamic nature encompassing biological, clinical, subjective, and socioeconomic factors. Opportunities to dynamically measure resilience were discussed during the ICFSR Task Force meeting, emphasizing potential biomarkers and areas of intervention. This article reports the results of the meeting and may serve to support future actions in the field.

Identifying Biomarkers for Biological Age: Geroscience and the ICFSR Task Force.

The International Conference on Frailty and Sarcopenia Research Task Force met in March 2020, in the shadow of the COVID-19 pandemic, to discuss strategies for advancing the interdisciplinary field of geroscience. Geroscience explores biological mechanisms of aging as targets for intervention that may delay the physiological consequences of aging, maintain function, and prevent frailty and disability. Priorities for clinical practice and research include identifying and validating a range of biomarkers of the hallmarks of aging. Potential biomarkers discussed included markers of mitochondrial dysfunction, proteostasis, stem cell dysfunction, nutrient sensing, genomic instability, telomere dysfunction, cellular senescence, and epigenetic changes. The FRAILOMICS initiative is exploring many of these through various omics studies. Translating this knowledge into new therapies is being addressed by the U.S. National Institute on Aging Translational Gerontology Branch. Research gaps identified by the Task Force include the need for improved cellular and animal models as well as more reliable and sensitive measures.

Establishment of normative biometric data for body composition based on computed tomography in a North American cohort.

BACKGROUND & AIMS: Accurate and reproducible biomarkers are required to allow a more personalized approach to patient care. Body composition is one such biomarker affecting outcomes in a range of surgical and oncological conditions. The aim of this study is to determine the age and sex specific distribution of body composition data, based on information gathered from computed tomography (CT). METHODS: This prospective study used healthy subjects from the medical records linkage of the Rochester Epidemiology Project, based in Minnesota, USA. Each patient had a CT scan without intravenous contrast performed between 1999 and 2001. Quantification was performed using previously validated semi-automated in-house developed software for body composition analysis. Subcutaneous adipose tissue area, visceral adipose tissue area, intermuscular adipose tissue area and skeletal muscle area were measured and indexed to subject height. Generalized Additive Models for Location, Scale and Shape were used to assess the location, scale, and shape of each variable across age, stratified by sex. Z-scores specific to sex were assessed for each of the parameters analyzed. Age-specific z-scores were calculated using the formula: Z = (Index Variable - µ)/σ or Z = (√ (Index Variable) - µ)/σ. RESULTS: There were 692 subjects enrolled in the study. The fitted model equation was offered for each variable with values presented for µ and σ. Modelling with penalized splines was performed for VAT index, IMAT index and total adipose tissue index. Scatterplots of each variable were produced with lines of Z-scores as a visual representation. CONCLUSION: This study offers comparative data to allow comparison amongst multiple populations. This will form an important reference for future research and clinical practice.

Building muscle, browning fat and preventing obesity by inhibiting myostatin.

The obesity epidemic is an overwhelming global health concern. Interventions to improve body weight and composition aim to restore balance between nutrient intake and energy expenditure. Myostatin, a powerful negative regulator of skeletal muscle mass, has emerged as a potential therapeutic target for obesity and type 2 diabetes mellitus because of the prominent role skeletal muscle plays in metabolic rate and insulin-mediated glucose disposal. In fact, inhibition of myostatin by genetic manipulation or pharmacological means leads to a hypermuscular and very lean build in mice. The resistance of myostatin-null mice to diet-induced obesity, fat mass accumulation and metabolic dysfunction has been presumed to be a result of their large skeletal muscle mass; however, in this issue of Diabetologia, Zhang et al. (doi: 10.1007/s00125-011-2304-4 ) provide evidence that myostatin inhibition also significantly impacts the phenotype of white adipose tissue (WAT). The authors reveal elevated expression of key metabolic genes of fatty acid transport and oxidation and, intriguingly, the presence of brown adipose tissue-like cells in WAT of myostatin-null mice. They also show that pharmacological inhibition of myostatin replicates several of the protective benefits conveyed by its genetic inactivation. Herein, these data, areas in need of further investigation and the evidence that implicates myostatin as a target for obesity and type 2 diabetes mellitus are discussed.