Senescence articles from across Nature Portfolio

Meguro et al. show an accumulation of p16^high senescent fibroblasts in the aging bladder that serves as a cancer-permissive niche and promotes tumor growth by secreting CXCL12. Inhibition of senescence or CXCL12 signaling suppresses bladder tumor growth.

Inhibition of S6 kinase 1 (S6K1) extends lifespan in mice, but the underlying mechanisms are not fully understood. Here Gallage et al. show that reduction of S6K signaling diminishes inflammation in the aged mouse liver via suppression of the senescence-associated secretory phenotype.

Transcription factors are regarded as desirable targets for drug discovery. Here novel chemical compounds that delay flower petal aging were identified by a cell-free high-throughput screening system targeting EPHEMERAL1, a NAC transcription factor.

Here the authors discovered that senescent cells increase protein synthesis through eIF5A regulation, involving polyamine metabolism and p53 pathways, crucial for immune surveillance and mitochondrial protein production in aging and cancer contexts.

The identification of senescent cells is a long-standing unresolved challenge, owing to their intrinsic heterogeneity and the lack of universal markers. In this Comment, we discuss the recent advent of machine-learning-based approaches to identifying senescent cells by using unbiased, multiparameter morphological assessments, and how these tools can assist future senescence research.

As we age, our cells acquire DNA mutations, resulting in cell-to-cell genomic heterogeneity. We characterized the landscape of mitochondrial DNA (mtDNA) heterogeneity in healthy human cells. Our observations provide deeper insight into the frequency of new mitochondrial mutations and the mechanisms that propagate low-level mutations in mtDNA over a lifetime.

A study from Ortega-Molina and colleagues uses mouse models with mildly elevated mTOR activity to investigate the stepwise process by which increased nutrient signaling affects healthy aging. These findings show how initial parenchymal damage caused by mTOR activity is followed by secondary myeloid inflammation, a multistage process that culminates in organ deterioration and reduced lifespan.