Development, stabilization and the shaping of ageing trajectories

Ageing integrates genetic, epigenetic, developmental and environmental influences across the lifespan, and reflects both damage accumulation and a progressive reduction of homoeostatic and adaptive capacity, narrowing the organism's functional range. These processes reflect the long-term behaviour of systems configured during development. Early-life processes define cellular, structural, endocrine and epigenetic landscapes that shape later-life trajectories, and are modulated by the exposome over time. Beyond the developmental origins of the health and disease framework, development more broadly shapes ageing. Developmental and ageing processes share molecular pathways, and developmental regulatory architectures can be maintained, repurposed or dysregulated later in life. Comparative biology further indicates that lifespan is associated with developmental tempo and long-term maintenance strategies, whereas organisms that retain plasticity and regenerative capacity often display attenuated ageing. Ageing appears linked not simply to development itself, but to the transition from developmental plasticity to stabilization. Ageing becomes more likely when development culminates in highly specialized, structurally stable and weakly renewable systems, which maximize function at the cost of reversibility and repair. This framework is particularly relevant to the brain, where development establishes long-lived, weakly renewable architectures. Ageing thus reflects the interactions between developmental constraints, lifelong environmental exposures and the stabilization of development. This article is part of the theme issue 'Developmental circuits in ageing'.