Computational identification of natural senotherapeutic compounds that mimic dasatinib based on gene expression data.

The major risk factor for chronic disease is chronological age, and age-related chronic diseases account for the majority of deaths worldwide. Targeting senescent cells that accumulate in disease-related tissues presents a strategy to reduce disease burden and to increase healthspan. The senolytic combination of the tyrosine-kinase inhibitor dasatinib and the flavonol quercetin is frequently used in clinical trials aiming to eliminate senescent cells. Here, our goal was to computationally identify natural senotherapeutic repurposing candidates that may substitute dasatinib based on their similarity in gene expression effects. The natural senolytic piperlongumine (a compound found in long pepper), and the natural senomorphics parthenolide, phloretin and curcumin (found in various edible plants) were identified as potential substitutes of dasatinib. The gene expression changes underlying the repositioning highlight apoptosis-related genes and pathways. The four compounds, and in particular the top-runner piperlongumine, may be combined with quercetin to obtain natural formulas emulating the dasatinib + quercetin formula.

Healthy Aging in Times of Extreme Temperatures: Biomedical Approaches.

Climate extremes and rising energy prices present interconnected global health risks. Technical solutions can be supplemented with biomedical approaches to promote healthy longevity in hot and cold conditions. In summer, reducing basal metabolic rate through mild caloric restriction or CR mimetics, such as resveratrol, can potentially be used to lower body temperature. In winter, activating brown adipose tissue (BAT) for non-shivering thermogenesis and improved metabolic health can help adaptation to colder environments. Catechins found in green tea and in other food could be alternatives to drugs for these purposes. This review examines and discusses the biomedical evidence supporting the use of CR mimetics and BAT activators for health benefits amid increasingly extreme temperatures.

Biomarkers of geroprotection and cardiovascular health: An overview of omics studies and established clinical biomarkers in the context of diet.

The slowdown, inhibition, or reversal of age-related decline (as a composite of disease, dysfunction, and, ultimately, death) by diet or natural compounds can be defined as dietary geroprotection. While there is no single reliable biomarker to judge the effects of dietary geroprotection, biomarker signatures based on omics (epigenetics, gene expression, microbiome composition) are promising candidates. Recently, omic biomarkers started to supplement established clinical ones such as lipid profiles and inflammatory cytokines. In this review, we focus on human data. We first summarize the current take on genetic biomarkers based on epidemiological studies. However, most of the remaining biomarkers that we describe, whether omics-based or clinical, are related to intervention studies. Then, because of their promising potential in the context of dietary geroprotection, we focus on the effects of berry-based interventions, which up to now have been mostly described employing clinical markers. We provide an aggregation and tabulation of all the recent systematic reviews and meta-analyses that we could find related to this topic. Finally, we present evidence for the importance of the "nutribiography," that is, the influence that an individual's history of diet and natural compound consumption can have on the effects of dietary geroprotection.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.1975638.

Transcription Factor Activation Profiles (TFAP) identify compounds promoting differentiation of Acute Myeloid Leukemia cell lines.

Repurposing of drugs for new therapeutic use has received considerable attention for its potential to limit time and cost of drug development. Here we present a new strategy to identify chemicals that are likely to promote a desired phenotype. We used data from the Connectivity Map (CMap) to produce a ranked list of drugs according to their potential to activate transcription factors that mediate myeloid differentiation of leukemic progenitor cells. To validate our strategy, we tested the in vitro differentiation potential of candidate compounds using the HL-60 human cell line as a myeloid differentiation model. Ten out of 22 compounds, which were ranked high in the inferred list, were confirmed to promote significant differentiation of HL-60. These compounds may be considered candidate for differentiation therapy. The method that we have developed is versatile and it can be adapted to different drug repurposing projects.

Ranking Biomarkers of Aging by Citation Profiling and Effort Scoring.

Aging affects most living organisms and includes the processes that reduce health and survival. The chronological and the biological age of individuals can differ remarkably, and there is a lack of reliable biomarkers to monitor the consequences of aging. In this review we give an overview of commonly mentioned and frequently used potential aging-related biomarkers. We were interested in biomarkers of aging in general and in biomarkers related to cellular senescence in particular. To answer the question whether a biological feature is relevant as a potential biomarker of aging or senescence in the scientific community we used the PICO strategy known from evidence-based medicine. We introduced two scoring systems, aimed at reflecting biomarker relevance and measurement effort, which can be used to support study designs in both clinical and research settings.