Spontaneous preterm birth (sPTB), affecting ~15 million infants annually, may be better understood as accelerated gestational aging rather than purely an infectious or inflammatory event. This narrative review synthesizes evidence that impaired mitochondrial oxidative phosphorylation, excess reactive oxygen species, and premature cellular senescence across the placenta, fetal membranes, decidua, cervix, and myometrium collectively activate labor pathways weeks or months before term. Key mechanistic nodes include disrupted mitophagy, ferroptosis, NAD⁺ depletion, inflammasome activation, and extracellular vesicle signaling — all converging through DAMPs and cytokine cascades at the maternal-fetal interface.
The "accelerated aging" framing is genuinely useful because it unifies previously siloed observations — oxidative stress, telomere shortening, p21/p53-driven senescence — under one biological clock model, and it directly imports a growing therapeutic toolkit from geroscience. Senolytics (e.g., dasatinib/quercetin), mitochondrial-targeted antioxidants (MitoQ), and NAD⁺ precursors are already in human trials for aging-related conditions, giving this reframing immediate translational traction. However, significant limitations apply: this is a narrative, not systematic, review, meaning selection bias in cited evidence is possible. Most mechanistic data derive from animal models or ex vivo tissue studies; causal human evidence is sparse. sPTB remains heterogeneous, and no single biomarker reliably predicts it. Incremental rather than paradigm-shifting for now, but the conceptual consolidation meaningfully narrows the target space for precision interventions.
