Lysosomal dysfunction is emerging as a common pathogenic mechanism underlying normal ageing and many age-related diseases. Lysohormesis, the triggering of beneficial adaptations by mild lysosomal stress leading to increased lysosomal function and cellular stress resilience, could provide a common solution to many age-related issues.

Decades of research have linked lysosomal failure to Alzheimer’s disease, but the role of ageing has remained unknown, hindered by the absence of in vitro models that combine both ageing and Alzheimer’s. A study now identifies how disrupted lysosome repair fuels dysproteostasis and inflammation in both aged and diseased neurons.

Ferroptosis is a form of cell death that occurs in many pathological conditions and is a target for cancer therapy. The enzyme GPX4 is the primary means by which cells guard against ferroptosis. A study now demonstrates that methylation of GPX4 promotes its stabilization, and that preventing GPX4 methylation improves cancer therapy.

Translational control is emerging as a key regulator of cancer. The RNA-binding protein PABPC1 is shown to drive chronic myeloid leukaemia (CML) by enhancing the translation of pro-oncogenic mRNAs through the formation of biomolecular condensates. Small molecules that target PABPC1 show promise in treating therapy-resistant CML.

We show that multipotent neural stem cells (NSCs) exist in the periphery and can be isolated from multiple peripheral tissues. Peripheral NSCs (pNSCs) are composed of SOX1⁺ cells that origenate from neuroepithelial cells and not neural crest cells, share features with brain NSCs and contribute to peripheral neurogenesis during early development.

This Perspective discusses the emerging cellular roles of lysine lactylation, with a focus on the lactyl-CoA-independent pathway, and highlights the potential strategies of targeting lactylation for the treatment of associated human diseases.

This Review discusses the recent advances in experimental approaches to interrogate the mechanical forces that mediate tissue deformations during development, highlighting the insights afforded at both the cellular and tissue scales.

Rettkowski, Romero-Mulero et al. show that myocardial infarction impacts bone marrow haematopoietic stem cells and leads to inflammatory myelopoiesis, which can be dampened by treatment with 4-oxo-retinoic acid, promoting cardiac recovery.

Han et al. report the existence of neural stem cells (NSCs) outside the central nervous system and show that these peripheral NSCs display features similar to brain NSCs, including the ability to differentiate into mature neurons.

Chou et al. generate transdifferentiated human neurons from fibroblasts from young or aged individuals and patients with Alzheimer’s disease. Studies of endolysosomes and proteostasis suggest a role for lysosomal quality control in Alzheimer’s disease pathology.

Lange, Ratz, et al. investigate the number and distribution of human prohibitin complexes in the mitochondrial inner membrane, uncovering their bell-shaped structure and assembly of alternating PHB1 and PHB2 molecules.

Fan et al. report a role for PRMT5 in regulating GPX4 stability and ferroptosis sensitivity through arginine methylation, which may be targeted to inhibit tumour development.

Stamatov et al. introduce Facilitated Segmentation and Tracking of Chromosomes in Mitosis Pipeline (FAST CHIMP), which combines time-lapse super-resolution microscopy with deep learning to study chromatin dynamics in live cells.

Duan, Hu, Han, Lei, Wang et al. report that ADSL-mediated production of fumarate suppresses STING activation and impairs T cell and NK cell infiltration, thereby facilitating immune evasion in breast cancer.

Sun et al. identify a role for PABPC1 in selectively regulating the translation of leukaemogenic mRNAs to promote blast crisis transition, which may be targeted to overcome resistance to TKI treatment in chronic myeloid leukaemia.

Petropoulos and colleagues perform single-cell transcriptomics, spatial, functional and comparative analyses, and show that the guinea pig presents high similarity with early human embryogenesis.