The 12 hallmarks of aging, mapped
The 2023 hallmark set, mapped to the network’s mechanism sites — honestly, with the gaps shown.
Descriptive, not prescriptive
The hallmarks are the field’s organizing scheme for the biology of aging. This map uses them to explain how the network is structured — which mechanism gets which site. It does not claim the network “targets aging,” and mapping a hallmark to a site is not a claim that anything slows or reverses it.
| # | Hallmark of aging | Mechanism site |
|---|---|---|
| 1 | Genomic instability Accumulating DNA damage and mutations across the nuclear and mitochondrial genome over a lifetime. | no dedicated site yet |
| 2 | Telomere attrition Progressive shortening of the protective chromosome-end caps, limiting replicative capacity. | TeloiX — live |
| 3 | Epigenetic alterations Age-associated changes in DNA methylation, histone modification and chromatin remodeling. | no dedicated site yet |
| 4 | Loss of proteostasis Declining protein quality control, chaperone function and clearance of damaged proteins. | no dedicated site yet |
| 5 | Disabled macroautophagy Reduced autophagic turnover of damaged organelles and aggregates (added as a distinct hallmark in 2023). | no dedicated site yet |
| 6 | Deregulated nutrient-sensing Dysregulation of the insulin/IGF-1, mTOR, AMPK and sirtuin nutrient-sensing network. | MtoriX — live |
| 7 | Mitochondrial dysfunction Declining mitochondrial efficiency, altered dynamics and increased reactive-oxygen-species leakage. | MitoiX — live |
| 8 | Cellular senescence Accumulation of growth-arrested cells with a pro-inflammatory secretory phenotype (SASP). | SenesiQ — live |
| 9 | Stem cell exhaustion Decline in the regenerative capacity of tissue-resident stem-cell pools. | no dedicated site yet |
| 10 | Altered intercellular communication Disrupted endocrine, neuronal and immune signaling between cells and tissues. | no dedicated site yet |
| 11 | Chronic inflammation Persistent, low-grade sterile inflammation ('inflammaging') that rises with age. | no dedicated site yet |
| 12 | Dysbiosis Age-associated shifts in the composition and function of the gut and other microbiota. | no dedicated site yet |
Source
Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. “Hallmarks of aging: An expanding universe.” Cell 186:243-278 (2023). DOI 10.1016/j.cell.2022.11.001.
DOI verification: verified_crossref (2026-07-13). Crossref returns DOI 10.1016/j.cell.2022.11.001 = 'Hallmarks of aging: An expanding universe', Cell (Elsevier BV), volume 186, pages 243-278. Title, container, volume and page range confirmed against the primary Crossref record.