Evidence brief · intervention
Gene therapy
Based on the provided sources, mesenchymal stem cells (MSCs) are recognized as promising vehicles for gene therapy, tissue engineering, and immunotherapy due to their multilineage potential, ease of genetic modification, and immunosuppressive properties [6]. Because MSCs exist at very low frequencies in their native niches, successful clinical application requires significant *in vitro* expansion [5, 6]. However, long-term culture can induce cellular senescence(definition) [5], presenting a technical challenge for producing the vast quantities of cells required for therapies [6].
In the broader context of aging interventions, gene therapy targeting fundamental aging mechanisms has shown preclinical efficacy. Specifically, telomerase gene therapy utilizing adeno-associated virus vectors administered to adult (1-year-old) and old (2-year-old) mice successfully delayed aging phenotypes and increased longevity without increasing the incidence of cancer [7]. Similarly, expression of the catalytic component of human telomerase (hTERT) extends the replicative life span of normal human somatic cells, such as endothelial cells, beyond normal senescence(definition) without causing neoplastic transformation [8].
The consensus across the literature highlights that stem cell technologies and telomerase-based genetic interventions hold strong potential for regenerative medicine and aging deceleration [3, 7, 8]. Nevertheless, open questions remain regarding how to optimize large-scale production without triggering in vitro senescence(definition) [5, 6], and how to fully reconcile interventions that manipulate fundamental longevity pathways with long-term safety profiles in humans. The strength of evidence ranges from well-established *in vitro* cellular mechanics and robust animal-model longevity trials [7, 8] to ongoing translational investigations in regenerative medicine [3].
Sources
- [1] Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver
- [2] Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow
- [3] Stem cell-based therapy for human diseases
- [4] Endoplasmic reticulum stress: molecular mechanism and therapeutic targets
- [5] Aging of mesenchymal stem cell in vitro
- [6] Characterization of the Optimal Culture Conditions for Clinical Scale Production of Human Mesenchymal Stem Cells
- [7] Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer
- [8] Human Endothelial Cell Life Extension by Telomerase Expression
- [9] A Generalised Epigenetic Clock Reveals Therapeutic Vulnerabilities Linked to Ageing in Cancer Cells
- [10] RECENT UNDERSTANDING OF EPIGENETIC AGING, REJUVENATION, AND LONGEVITY PRINCIPLES FOR REVERSE AGING