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.

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The highest risk factor for chronic diseases 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.Our goal was the computational identification of senotherapeutic repurposing candidates that potentially eliminate senescent cells, based on their similarity in gene expression effects to dasatinib, a tyrosine-kinase inhibitor that induces apoptosis in certain senescent cell types, and that is frequently used as a senolytic together with quercetin.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 (D+Q) formula that is frequently used in clinical trials targeting senescent cells.

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.

Nutritional interventions in healthy individuals may be particularly informative if high, but not excessive, amounts of specific healthy foods are taken to maximize effects without sacrificing safety. We hypothesized that high amounts of polyphenols taken on single days may eliminate senescent blood cells. We conducted a ten-week parallel-group controlled randomized open trial with an escalation of consumption, up to ~4kg fresh strawberries weekly, plus 200g dried strawberries and 240g capers in olive oil on three single "seno-intervention" days, in 168 healthy elderly people aged 50-80 years. Two primary endpoints, LDL cholesterol and high sensitive CRP, were prespecified. We found a significant decline in LDL cholesterol, and in CRP by ~50% in all groups with seno-intervention days (limited to participants with increased baseline values). LDL levels were reduced by 0.0174 mmol/L for any single 500g-increment in the weekly fresh strawberry intake of the average participant. Gene expression analyses of whole blood suggested improvement of mitochondrial and immunological function, suppression of inflammation (in high-intervention groups), and positive regulation of apoptotic signaling (in the highest-intervention group). Overall, a medium-term nutritional intervention improved lipid and inflammation status, and provided specific hints for apoptotic/senolytic effects.