Engineered cardiac transcription factor restores vision and reduces frailty in aging mice
A genome-scale screen in retinal cells identified NKX2-5 variants that conferred oxidative resilience and improved physical function without detectable toxicity.
bioRxiv · Lu YRR et al. · Paper published 30 Sep 2026
In a new preprint, researchers tested retinal pigment epithelium cells and aging mice to discover genes that confer resistance to oxidative damage. Using an unbiased, genome-scale open reading frame screen, the team identified nine protective factors, including antioxidant genes and a regulator of epithelial-to-mesenchymal transition. Three candidates reduced transcriptomic age, notably the cardiac transcription factor NKX2-5. Domain dissection revealed that its homeodomain was dispensable, enabling the development of an engineered variant, NKX2-5ΔHD, which retained protective activity with no detectable toxicity over 14 months. Subretinal delivery of NKX2-5ΔHD restored electrophysiological and visual function in middle-aged mice, while systemic administration improved grip strength and lowered frailty scores in late-aged mice.
Why it matters
The findings show that unbiased gain-of-function screening can identify resilience factors from non-retinal lineages that mitigate oxidative damage and tissue decline during aging.
Caveats
The study was conducted exclusively in cell cultures and mice, and the results appear in a preprint that has not yet completed peer review.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
A genome-scale ORF screen for resilience factors that protect the RPE and restore vision in aged mice
Lu YRR, Shen H, Kajderowicz K et al.
bioRxiv · 30 Sep 2026 · Preprint, not yet peer-reviewed
- Relevance
- Core geroscience
- News value
- Important
- Evidence
- Animals
- Status
- Preprint
Latest stories
Gastrodia elata polysaccharide extends worm lifespan and mitigates age-related deficits in mice
The treatment reduced oxidative stress, suppressed inflammation, and remodeled the gut microbiome in naturally aging mice while prolonging survival in nematodes.
Food science & nutrition · Shi H et al.
Simulated microgravity increases transcriptomic age in human organoids
Culturing human neural, cardiac, and tonsil models in rotating-wall vessels for 24 hours also shifted contraction dynamics and immune gene expression.
bioRxiv · Mu W-C et al.
Rank normalization resolves distinct proteome degradation pathways in cultured cells
A percentile-based normalization method reveals substrate preferences between proteasomal and lysosomal clearance systems in cultured cells.
bioRxiv · Gao Z et al.
Melissic acid reduces senescence in human stem cells via cAMP signaling
A screen of 800 natural compounds identified a phytochemical that activates autophagy and restores cell-cycle activity in models of cellular exhaustion.
Frontiers in pharmacology · Yang K et al.