Can iPSCs Turn Back Time? Prospects and Pitfalls in Age Reversal

Aging is characterized by the progressive loss of cellular function, the accumulation of epigenetic and transcriptional changes, and a decline in tissue homeostasis. Induced pluripotent stem cells (iPSCs), derived from somatic cells through expression of Yamanaka factors (OCT4, SOX2, KLF4, MYC; OSKM), undergo epigenetic rejuvenation, effectively resetting their biological age. Partial reprogramming, characterized by the transient or cyclic expression of reprogramming factors, has emerged as a promising method to reverse aging hallmarks without erasing cellular identity. This study aims to synthesize findings from studies on iPSC-based age reversal, covering mechanisms, therapeutic potential, challenges, and translational hurdles. While partial reprogramming can restore youthful gene expression, DNA methylation patterns, and mitochondrial function, and reduce senescence markers, major safety concerns remain, including genomic instability, tumorigenesis, and incomplete control over identity retention. The field is rapidly progressing, yet fundamental questions about long-term safety, efficacy, and optimal protocols must be resolved before clinical translation.