# The pursuit of understanding human longevity

**Authors:** Pawel Kordowitzki, Kejun Ying

PMC · DOI: 10.1038/s41514-026-00339-z · NPJ Aging · 2026-02-05

## TL;DR

The paper explores how people can live past 100 years by combining genetic, metabolic, and lifestyle factors.

## Contribution

It highlights that extreme age and poor health are not inherently linked, emphasizing multifactorial resilience.

## Key findings

- Longevity involves protective genetics and efficient metabolism.
- Low inflammation and healthy lifestyle choices contribute to living longer.
- Centenarians and Blue Zones show the synergy of biological and environmental factors.

## Abstract

Precise recommendations for humans to reach more than 100 years remain elusive. A recent multiomics study revealed that extreme age and poor health are not inherently linked. Longevity stems from a multifactorial resilience that involves protective genetics, efficient metabolism, low inflammation, and favorable lifestyle choices. Insights from centenarians and Blue Zones suggest that healthy aging is rooted in the synergistic interplay of biological, environmental, and above mentioned factors.

## Full-text entities

- **Genes:** HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, RFX5 (regulatory factor X5) [NCBI Gene 5993] {aka MHC2D3, MHC2D5}, FGF21 (fibroblast growth factor 21) [NCBI Gene 26291], IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, RELA (RELA proto-oncogene, NF-kB subunit) [NCBI Gene 5970] {aka AIF3BL3, CMCU, NFKB3, p65}, STAT1 (signal transducer and activator of transcription 1) [NCBI Gene 6772] {aka CANDF7, IMD31A, IMD31B, IMD31C, ISGF-3, STAT91}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, STAT2 (signal transducer and activator of transcription 2) [NCBI Gene 6773] {aka IMD44, ISGF-3, P113, PTORCH3, STAT113}, PRKAA1 (protein kinase AMP-activated catalytic subunit alpha 1) [NCBI Gene 5562] {aka AMPK, AMPK alpha 1, AMPKa1}
- **Diseases:** chronic diseases (MESH:D002908), injuries (MESH:D014947), cardiovascular diseases (MESH:D002318), inflammation (MESH:D007249), infections (MESH:D007239), neurodegenerative disorders (MESH:D019636), cancer (MESH:D009369), infectious diseases (MESH:D003141)
- **Chemicals:** NAD + (MESH:D009243), alcohol (MESH:D000438), lipid (MESH:D008055), methionine (MESH:D008715), sugary (-), sodium (MESH:D012964)
- **Species:** Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Nicotiana tabacum (American tobacco, species) [taxon 4097], Homo sapiens (human, species) [taxon 9606], gut metagenome (species) [taxon 749906], Bifidobacterium (genus) [taxon 1678]
- **Mutations:** rs2069837

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12876948/full.md

## References

2 references — full list in the complete paper: https://tomesphere.com/paper/PMC12876948/full.md

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Source: https://tomesphere.com/paper/PMC12876948