Cellular senescence suppresses cancer by irreversibly arresting cell proliferation. Senescent cells acquire a pro-inflammatory senescence-associated secretory phenotype. Many genotoxic chemotherapies target proliferating cells non-specifically, often with adverse reactions. In accord with prior work, we show that several chemotherapeutic drugs induce senescence of primary murine and human cells. Using a transgenic mouse that permits tracking and eliminating senescent cells, we show that therapy-induced senescent (TIS) cells persist and contribute to local and systemic inflammation. Eliminating TIS cells reduced several short- and long-term effects of the drugs, including bone marrow suppression, cardiac dysfunction, cancer recurrence and physical activity and strength. Consistent with our findings in mice, the risk of chemotherapy-induced fatigue was significantly greater in humans with increased expression of a senescence marker in T-cells prior to chemotherapy. These findings suggest that senescent cells can cause certain chemotherapy side effects, providing a new target to reduce the toxicity of anti-cancer treatments.

Cellular senescence is a common outcome of various anticancer interventions.Senescence-associated secretory phenotypes (SASPs) have pro-tumorigenic functions.Evidence exists of increased cellular senescence in patients treated for various types of cancer.Therapy-induced senescence can cause cancer metastasis and relapse and several adverse reactions to cancer treatments.Pharmacological interference with detrimental senescence might be considered to improve the efficacy of cancer treatments and improve the life quality of treated patients.

Colobines are a unique group of Old World monkeys that principally eat leaves and seeds rather than fruits and insects. We report the sequencing at 146× coverage, de novo assembly and analyses of the genome of a male golden snub-nosed monkey (Rhinopithecus roxellana) and resequencing at 30× coverage of three related species (Rhinopithecus bieti, Rhinopithecus brelichi and Rhinopithecus strykeri). Comparative analyses showed that Asian colobines have an enhanced ability to derive energy from fatty acids and to degrade xenobiotics. We found evidence for functional evolution in the colobine RNASE1 gene, encoding a key secretory RNase that digests the high concentrations of bacterial RNA derived from symbiotic microflora. Demographic reconstructions indicated that the profile of ancient effective population sizes for R. roxellana more closely resembles that of giant panda rather than its congeners. These findings offer new insights into the dietary adaptations and evolutionary history of colobine primates.Knowledge of the patterns and processes underlying the evolution of alternative dietary strategies in nonhuman primates is critical to understanding hominin evolution, nutritional ecology and applications in biomedicine 1 . Colobines, a group of Old World monkeys, serve as an important model organism for studying the evolution of the primate diet because of their adaptation to folivory: they primarily eat leaves and seeds rather than fruits and insects as their major food source. In their specialized and compartmentalized stomachs, colobines allow symbiotic bacteria in the foregut to ferment structural carbohydrates and then recover nutrients by digesting the bacteria 2 . This strategy is similar to that used by other foregut fermenters found in an evolutionarily distantly related group of mammals (for example, artiodactyls). Although a number of primate genomes have been sequenced thus far, high-quality genome sequence information is absent for Asian and African colobines, a key group for elucidating the evolution and adaptation of primates as a whole. Snub-nosed monkeys (Rhinopithecus species) are a group of endangered colobines, which were once widely distributed in Asia but are now limited to mountain forests in China and Vietnam 3 (Supplementary Fig. 1).The golden snub-nosed monkey (GSM, R. roxellana) is recognized as an iconic endangered species in China for its golden coat, blue facial coloration, snub nose and specialized life history. Among its congeners, the black-white snub-nosed monkey (R. bieti), endemic to the Tibetan plateau, has the highest altitudinal distribution (>4,000 m above sea level) of any nonhuman primate. Given the above features and the fact that Rhinopithecus species consume difficult-to-digest foods that contain tannins (for example, leaves and pine seeds), we expected to identify genetic adaptations that enhance the breakdown of toxins, improve the regulation of energy metabolism and facilitate the digestion of symbiotic microbacteria. RESULTS Genomic sequences and the accumulation of...