Gene therapy

**Consensus and Main Findings** Stem cell technologies, including human pluripotent stem cells (hPSCs) and multipotent mesenchymal stem cells (MSCs), have emerged as key players in regenerative medicine and gene therapy [3]. MSCs are particularly promising for gene therapy and tissue engineering due to their multilineage potential, immunosuppressive abilities, and ease of genetic modification [6]. To meet the high cell numbers required for clinical applications, methods for expanding various stem cell populations—such as adult human liver stem cells and fetal-derived MSCs—are actively investigated [1, 2], though maintaining these cells in culture often requires addressing in vitro senescence and long-term stability [5]. Beyond cell-based modifications, direct genetic interventions targeting fundamental aging mechanisms, such as adeno-associated virus-mediated telomerase gene therapy in adult and old mice, have been demonstrated to delay aging and increase longevity without elevating cancer incidence [7].

**Open Questions** Despite these advances, critical questions remain regarding the optimization and long-term safety of stem cell and gene therapies. For MSCs, the necessity of extensive *in vitro* expansion prior to clinical use introduces challenges related to cellular senescence and altered phenotype [5]. Furthermore, while telomerase gene therapy successfully extends healthspan and lifespan in murine models [7], translating such genetic interventions safely to humans requires resolving complex interactions between genetic modifications, systemic aging hallmarks (such as loss of splicing homeostasis [10] or endoplasmic reticulum stress [4]), and long-term oncogenic risks.