This hypothesis proposes that the functional outcome of senescent cells in tissue repair hinges on their NAD+‑dependent SASP composition, and that indiscriminate senolytic clearance removes a reversible, pro‑regenerative state before it can't be rescued by metabolic rejuvenation. In young or metabolically competent tissues, transient senescent fibroblasts and immune cells upregulate NAD+ biosynthesis, which fuels SIRT1‑mediated deacetylation of NF‑κB and shifts the secretome from a chronic, inflammatory profile to a transient, PDGF‑AA‑rich, pro‑regenerative SASP that accelerates reepithelialization, promotes myofibroblast differentiation, and limits fibrosis12. When NAD+ levels fall—as occurs in aged or diseased microenvironments—SIRT1 activity drops, NF‑κB remains hyperacetylated, and the SASP skews toward sustained IL‑6, IL‑8, and MMP secretion that impairs stem cell function and fosters fibrosis34. Critically, this NAD+‑SASP axis it's reversible: pharmacological NAD+ precursors (e.g., NR, NMN) or genetic overexpression of NAMPT restore the youthful secretome in cultured senescent fibroblasts and senescent T cells, enabling them to recruit macrophages via CCL2 and to secrete VEGF‑A that supports angiogenesis56. Consequently, senolytic agents administered before NAD+ replenishment eliminate cells that they're able to coax back into a reparative phenotype, whereas senolytics given after metabolic rescue selectively clear only those senescent cells that have failed to re‑engage the regenerative program, preserving the beneficial cohort. Testable predictions: (1) In a murine excisional wound model, NAD+ boosting prior to senolytic treatment will increase the proportion of p21^high/p16^low senescent fibroblasts expressing PDGF‑AA and decrease fibrosis compared with senolytic alone; (2) Single‑cell RNA‑seq of wound‑derived senescent cells will reveal a NAD+‑responsive SASP module that correlates with macrophage recruitment markers and predicts healing speed; (3) Genetic ablation of NAMPT in senescent fibroblasts will block the shift to a PDGF‑AA‑enriched SASP despite NAD+ supplementation, resulting in delayed reepithelialization and persistent inflammation. Falsification would occur if NAD+ augmentation fails to alter SASP composition or if senolytic timing shows no difference in regenerative outcomes, indicating that senescent cell function is independent of NAD+‑SIRT1 signaling. This reframes senolytics from a blunt depletion tool to a context‑dependent clearance strategy that preserves metabolically competent, repair‑promoting senescent cells while removing truly deleterious ones.