Hallmarks of aging
The hallmarks of aging is a framework published in 2013 by Carlos López-Otín, Maria Blasco, Linda Partridge, Manuel Serrano, and Guido Kroemer that groups the cellular and molecular processes accompanying aging into a short list of named features. The original paper listed nine hallmarks and sorted them into three tiers: primary causes of damage, responses that turn harmful when sustained, and downstream consequences. A 2023 update expanded the list to twelve. The framework functions as an organizing map for aging research and as a checklist for interventions that might affect several age-related diseases at once.12
The original nine
The 2013 paper assigned each hallmark to one of three tiers according to its proposed role in the causal chain.1
| Hallmark | Tier | Process |
|---|---|---|
| Genomic instability | Primary | Accumulation of DNA damage and mutations |
| Telomere attrition | Primary | Shortening of chromosome ends with each replication ([[telomeres |
| Epigenetic alterations | Primary | Changes in DNA methylation and chromatin organization |
| Loss of proteostasis | Primary | Decline in protein folding and clearance |
| Deregulated nutrient sensing | Antagonistic | Altered [[igf-1 |
| Mitochondrial dysfunction | Antagonistic | Reduced mitochondrial function and altered signaling |
| Cellular senescence | Antagonistic | Accumulation of arrested cells ([[cellular-senescence |
| Stem cell exhaustion | Integrative | Reduced regenerative capacity |
| Altered intercellular communication | Integrative | Changed circulating signals and chronic inflammation ([[sasp |
The tiers describe roles in the model. Primary hallmarks generate damage. Antagonistic hallmarks began as protective responses and produce harm when they persist. Integrative hallmarks follow from the first two and explain the organism-level phenotype. The paper argued that the hallmarks interact and that a drug acting on several of them could delay multiple age-related diseases, which made the framework a template for intervention research.1
The 2023 expansion
The 2023 update added disabled macroautophagy, chronic inflammation, and dysbiosis for a total of twelve hallmarks. It also restated three criteria that a hallmark should meet: it appears with age, experimentally accentuating it accelerates aging, and intervening on it decelerates, stops, or reverses aspects of the aging process. The updated paper presented the hallmarks as interconnected with one another and with a parallel set of proposed hallmarks of health.2
Use in research
The framework supplies a shared vocabulary for a field that studies many organisms and cell types. It groups otherwise separate lines of work, which lets a reader place cellular senescence, telomere biology, mTOR signaling, and apoptosis within one outline. The template came from the cancer literature: Hanahan and Weinberg had organized cancer biology into hallmarks in 2000 and 2011, and the aging framework followed that form.
Criticism
Gems and de Magalhães argued in 2021 that the hallmarks of aging describe features that accompany age while the hallmarks of cancer explain how cancer develops. In their reading the aging framework is a checklist of major research areas whose structure can resemble a causal account, and they called for a mechanistic paradigm in its place. The critique targets the framework’s explanatory role, and the individual hallmarks remain active areas of research.3
See also
References
Footnotes
- López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194–1217. doi:10.1016/j.cell.2013.05.039. ↩↩2↩3
- López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: an expanding universe. Cell. 2023;186(2):243–278. doi:10.1016/j.cell.2022.11.001. ↩↩2
- Gems D, de Magalhães JP. The hoverfly and the wasp: a critique of the hallmarks of aging as a paradigm. Ageing Research Reviews. 2021;70:101407. doi:10.1016/j.arr.2021.101407. ↩