Genomic instability
Hallmark of aging61 papers13 findings
Human cohorts and cell models link genomic instability to age, genetic variants, and somatic mutations, whilst mouse studies show that gene knockouts induce it. Reviews describe transposable element reactivation, oxidative stress, and associations with senescence and atherosclerosis.
- Humans7
- Animals11
- Model organisms4
- Cells13
Interventions
3NPM1 knockdown
upin human cells1
1 study
NPM1 knockdown
upin human cells1
NPM1 knockdown increases genomic instability in human cells.
Cellsunder Progerin expressiondepletion
Nucleoli buffer displaced heterochromatin to limit premature aging programs in cells · bioRxiv · 1 Oct 2026 · Preprint
Leptin
downin pig cells1
1 study
Leptin
downin pig cells1
Leptin decreases genomic instability in pig cells.
Cellsunder heat stressSertoli cellmales
Leptin mitigates heat stress-induced senescence in porcine Sertoli cells through modulation of ATM-p53, ERK1/2, and AMPK-mTORC1 signaling · Journal of animal science · 26 Sep 2026
AGTR2 knockout
upin mice1
1 study
AGTR2 knockout
upin mice1
AGTR2 knockout induces genomic instability in mice.
Animals
Lack of the AT2R receptor accelerates cardiac senescence and fibrosis in aging mice · Clinical science (London, England : 1979) · 25 Sep 2026
Effects
1Cellular senescence
upin reviews1
1 study
Cellular senescence
upin reviews1
Genomic instability induces cellular senescence.
“When these protective mechanisms fail, persistent DNA damage can promote apoptosis or senescence, alter inflammatory signaling and extracellular communication”
Reviewwhen protective mechanisms failmacrophage
Genomic Stress and DNA Repair During Macrophage Differentiation and Inflammatory Activation · International journal of molecular sciences · 17 Sep 2026
Upstream
4Transposable elements
upin humans1
1 study
Transposable elements
upin humans1
transposable elements increase genomic instability in humans.
Reviewupon reactivation during aging, chronic inflammation, and cancer
The regulatory and therapeutic potential of transposable elements in cancer and inflammatory diseases · Pharmacology & therapeutics · 25 Sep 2026
Somatic single nucleotide variants
upin human cells1
1 study
Somatic single nucleotide variants
upin human cells1
Somatic single nucleotide variants increase genomic instability in human cells (>12-fold).
Cellsat end of life compared to mouse neuronscerebral cortical neuron
Human neurons accumulate far more mutations over lifespan than shorter-lived mammals · bioRxiv : the preprint server for biology · 24 Sep 2026 · Preprint
Oxidative stress and ROS signalling
upin reviews1
1 study
Oxidative stress and ROS signalling
upin reviews1
Oxidative stress and ROS signalling induces genomic instability.
“Excessive ROS/RNS trigger irreversible DNA damage and metabolic disorders, leading to inflammation and apoptosis.”
Reviewexcessive ROS/RNS
Oxidative Stress in Animals: A Systematic Analysis from Signaling Pathways to Biological Effects · Life (Basel, Switzerland) · 11 Sep 2026
TE activity
upin humans1
1 study
TE activity
upin humans1
TE activity increases genomic instability in humans.
“TE activity contributes to genomic instability and has been implicated in aging, cancer, neurological disorders, chromatin organization, and epigenetic regulation.”
Review
Active Human Transposable Elements: Long-Read Sequencing Technologies, Computational Analysis, and Implications for Human Disease · Biomolecules · 27 Aug 2026
Associations
5DNMT3A knockout
upin silico1
1 study
DNMT3A knockout
upin silico1
DNMT3A knockout is associated with genomic instability in silico.
In silicoin lymphomas
TET enzyme deficiency drives the selection of specific aneuploid cells in mice · bioRxiv · 1 Oct 2026 · Preprint
Tet2/3 deletion
upin mice1
1 study
Tet2/3 deletion
upin mice1
Tet2/3 deletion is associated with genomic instability in mice.
Animalsfollowing transplantation into recipient miceinvariant natural killer T cell
TET enzyme deficiency drives the selection of specific aneuploid cells in mice · bioRxiv · 1 Oct 2026 · Preprint
Age
downin humans1
1 study
Age
downin humans1
Age is associated with genomic instability in humans.
Humansage at death in FTLD-TDP type Csuperior temporal gyrus
Single-neuron sequencing reveals widespread low-frequency somatic mutations in dementia brains · bioRxiv : the preprint server for biology · 22 Sep 2026 · Preprint
PMF1
mixedin humans1
1 study
PMF1
mixedin humans1
PMF1 is associated with genomic instability in humans.
Humansmissense variantleukocyte
Inherited genetic variants influence age-associated mosaic chromosomal errors in human blood · medRxiv : the preprint server for health sciences · 9 Sep 2026 · Preprint
Atherosclerosis
upin humans1
1 study
Atherosclerosis
upin humans1
Genomic instability is associated with atherosclerosis in humans.
Reviewclonal evolution in tissue microenvironmentatherosclerotic plaque
Inherited and somatic components in the pathogenetics of common diseases · Vavilovskii zhurnal genetiki i selektsii · 1 Sep 2026
Latest
61Single-neuron sequencing reveals widespread low-frequency somatic mutations in dementia brains
Human neurons from frontotemporal lobar degeneration patients showed ultra-low-frequency TARDBP variants that were less abundant in individuals who died at older ages.
bioRxiv : the preprint server for biology · Bidhan V et al.
Human neurons accumulate far more mutations over lifespan than shorter-lived mammals
Cortical neurons gain mutations at similar yearly rates across six species, leaving aged humans with uniquely high mutational burdens and transcriptomic dysregulation.
bioRxiv : the preprint server for biology · Caglayan E et al.
Human lymph node fibroblasts show cellular aging features before rheumatoid arthritis onset
Fibroblasts from individuals at risk for rheumatoid arthritis exhibit impaired adipogenic differentiation and downregulated DNA repair and cell cycle pathways.
RMD open · Jiménez-Martínez M et al.
Aging impairs blastema formation and tissue regeneration in Cladonema jellyfish
Older jellyfish medusae exhibit cell loss, heightened DNA damage, and defective wound closure that limit complex tentacle regrowth.
Aging cell · Kanehisa R et al.
TET enzyme deficiency drives the selection of specific aneuploid cells in mice
Loss of DNA methylation regulators accelerates clonal expansion by enriching rare pre-existing chromosomal gains such as chromosome 17 trisomy.
bioRxiv · López-Moyado IF et al.
Proteomic organ clocks predict mortality but trail established physiological and epigenetic biomarkers
In an older Scottish cohort, epigenetic age and brain volume outmatched plasma proteomic organ clocks for predicting long-term all-cause mortality.
Aging cell · Pyrgioti M et al.
Inhibiting CHK2 improves oocyte quality and reduces ovarian inflammation in aged mice
A multi-omic analysis shows that defective luteal resolution and CHK2-driven inflammation drive ovarian aging, but drug inhibition restores oocyte maturation.
bioRxiv · Yang L et al.
Nucleoli buffer displaced heterochromatin to limit premature aging programs in cells
In cells expressing progerin, the nucleolus sequesters released lamina-associated domains to preserve gene repression and prevent worsening DNA damage.
bioRxiv · Mungo C et al.
Somatic blood mutations associate with accelerated frailty and functional decline in humans
In a preprint analyzing over 730,000 adults, researchers linked clonal hematopoiesis to faster physical decline mediated by T-cell changes.
medRxiv · Zhao K et al.