Senotypes define the diverse landscape of senescent cells.

Authors

Marissa J Schafer, Nathan Basisty, Ann V Hertzel, Alexandra N Rindone, Jennifer H Elisseeff, Vidyani Suryadevara, Constantin Aliferis, Paul D Robbins, Laura J Niedernhofer, Karl N Miller, Peter D Adams, Vilas Menon, Hemali Phatnani, Joao F Passos, Birgit Schilling, Simon Melov, Nicola Neretti, Darren J Baker

Published in

Nature aging. Jul 29, 2026. Epub Jul 29, 2026.

Abstract

Cellular senescence was initially defined in vitro as a stable cell-cycle arrest that occurs after repeated replication, but it is now recognized as a heterogeneous state shaped by cell type, species, senescence-inducing stress, tissue microenvironment and time. To organize this complexity, we propose the term 'senotype' to classify senescent cells by their inputs, molecular features and functional effects. We outline a practical framework incorporating: (1) cell identity and context; (2) inducing mechanism; (3) temporal stage; (4) multimodal molecular and structural features; and (5) physiological or pathological functions. Experimentally defined senotypes can serve as references for interpreting tissue-derived senotypes, where parameters may be incomplete. Senotypes should be anchored in combinations of core hallmarks (that is, durable cell-cycle arrest, altered secretory profiles, macromolecular or organelle damage, disrupted homeostasis) rather than single markers. Advances in single-cell, spatial, proteomic and computational methods enable rigorous senotype characterization, improving consistency and accelerating development of targeted senotherapeutics.

PMID:
42527677
Bibliographic data and abstract were imported from PubMed on 30 Jul 2026.

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