Microgravity Remodels Longevity Networks in Astronaut PBMCs: Integrated Findings of Telomere Elongation, DNA Repair Responses, and miRNA Suppression

Cam, E.; Demir, O.; Tekirdagli, B.; Bulut, D.; Guzenge, E.; Harputoglu Efendi, S. N.; Yolver, B.; Kolay, K.; Kavakli, I. H.; Karouia, F.; Aydin, B.; Tastan, C.

doi:10.64898/2025.12.20.695716

bioRxiv · 10.64898/2025.12.20.695716

Microgravity Remodels Longevity Networks in Astronaut PBMCs: Integrated Findings of Telomere Elongation, DNA Repair Responses, and miRNA Suppression

Cam, E.·Demir, O.·Tekirdagli, B.·Bulut, D.·Guzenge, E.·Harputoglu Efendi, S. N.·Yolver, B.·Kolay, K.·Kavakli, I. H.·Karouia, F.·Aydin, B.·Tastan, C.

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Abstract

Microgravity provides a unique environment for elucidating the fundamental mechanisms of human aging. In the Microgravity Associated Genetics (MESSAGE) Science Mission--Turkiyes first human space biology experiment--we performed an integrative analysis of telomere dynamics, transcriptomic remodeling, and microRNA regulation in peripheral blood mononuclear cells (PBMCs) collected before launch (L-7day), after suborbital ascent (L+3hrs), and during days 4-10 aboard the International Space Station (ISS). Spaceflight induced a striking early elongation of telomeres, accompanied by transcriptional activation of DNA repair, oxidative stress mitigation, mitochondrial homeostasis, and immune regulatory pathways. Concurrently, microgravity triggered robust suppression of longevity-associated microRNAs, including members of the miR-17-92, miR29, and miR34 families, suggesting coordinated epigenetic reprogramming of genome stability and stress responses. Notably, the adaptor protein gene AP2A1, recently implicated in cellular rejuvenation and mechanotransductive aging processes, emerged as a consistently microgravity-responsive hub, linking cytoskeletal signaling to telomere maintenance and DNA repair networks. Together, these findings reveal that short-duration spaceflight initiates a multi-layered molecular longevity program in human immune cells, characterized by telomere extension, stabilization of genome maintenance pathways, and suppression of aging-associated miRNA regulators. This systems-level view provides foundational insight into how human biology adapts to short-term microgravity exposure and identifies AP2A1-centered networks as promising targets for enhancing astronaut health and performance and ultimately understanding terrestrial aging.

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Cam, E., Demir, O., Tekirdagli, B., Bulut, D., Guzenge, E., Harputoglu Efendi, S. N., Yolver, B., Kolay, K., Kavakli, I. H., Karouia, F., Aydin, B., Tastan, C.. 2025-12-22. Microgravity Remodels Longevity Networks in Astronaut PBMCs: Integrated Findings of Telomere Elongation, DNA Repair Responses, and miRNA Suppression. https://doi.org/10.64898/2025.12.20.695716

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