The harmonies played by miR-302/367 cluster in pluripotency, reprogramming, and rejuvenation

TL;DR

This paper reviews how the miR-302/367 cluster helps control cell fate, reprogramming, and aging, with potential for treating age-related diseases.

Contribution

The paper highlights the miR-302/367 cluster's dual role in promoting pluripotency and countering aging, with potential for rejuvenation therapies.

Findings

The miR-302/367 cluster suppresses aging markers like p16INK4a and p21 during reprogramming.

It reduces oxidative stress and fibrosis, suggesting therapeutic use in age-related conditions.

Combining miR-302/367 with delivery systems like lipid nanoparticles could enable targeted rejuvenation.

Abstract

The conserved, pluripotency-associated miR-302/367 cluster coordinates cell fate and aging via epigenetic, cell cycle, and signaling regulation. Highly expressed in pluripotent stem cells and silenced during differentiation, it promotes efficient somatic cell reprogramming by suppressing senescence mediators (eg, p16INK4a, p21) and replacing oncogenes such as c-Myc to minimize tumorigenic risks. Beyond pluripotency, the miR-302/367 cluster reduces oxidative stress, mitochondrial dysfunction, and fibrosis, indicating therapeutic potential in age-associated conditions such as neurodegenerative, ocular, and fibrotic diseases. This review summarizes the dual ability of miR-302/367 cluster in promoting cell state transitions and transiently resetting cellular aging to enable healthspan extension. We critically discuss the pivotal role of miR-302/367 cluster in pluripotency and reprogramming while countering aging hallmarks. Finally, we explore how combining single-miRNA therapeutics with clinically viable delivery systems (lipid nanoparticles and extracellular vesicles) can link cellular reprogramming with targeted rejuvenation therapies.

Graphical Abstract

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