Miliotou Eleni, de Lázaro Irene
Department of Biomedical Engineering, NYU Tandon School of Engineering, New York University, New York, New York, USA.
Cardiovascular Research Center, Leon H. Charney Division of Cardiology, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA.
Cells Tissues Organs. 2024;213(6):538-550. doi: 10.1159/000539415. Epub 2024 May 20.
With the elderly population projected to double by 2050, there is an urgent need to address the increasing prevalence of age-related debilitating diseases and ultimately minimize discrepancies between the rising lifespan and stagnant health span. Cellular reprogramming by overexpression of Oct3/4, Klf4, Sox2, and cMyc (OKSM) transcription factors is gaining attention in this context thanks to demonstrated rejuvenating effects in human cell cultures and live mice, many of which can be uncoupled from dedifferentiation and loss of cell identity.
Here, we review current evidence of the impact of cell reprogramming on established aging hallmarks and the underlying mechanisms that mediate these effects. We also provide a critical assessment of the challenges in translating these findings and, overall, cell reprogramming technologies into clinically translatable antiaging interventions.
Cellular reprogramming has the potential to reverse at least partially some key hallmarks of aging. However, further research is necessary to determine the biological significance and duration of such changes and to ensure the safety of cell reprogramming as a rejuvenation approach. With this review, we hope to stimulate new research directions in the quest to extend health span effectively.
预计到2050年老年人口将翻倍，迫切需要应对与年龄相关的衰弱性疾病患病率不断上升的问题，并最终尽量减少不断延长的寿命与停滞不前的健康寿命之间的差距。在这种背景下，通过过表达Oct3/4、Klf4、Sox2和cMyc（OKSM）转录因子进行细胞重编程受到关注，这得益于其在人类细胞培养物和活体小鼠中显示出的年轻化作用，其中许多作用可以与去分化和细胞身份丧失脱钩。
在这里，我们综述了细胞重编程对既定衰老标志的影响以及介导这些作用的潜在机制的现有证据。我们还对将这些发现以及总体上细胞重编程技术转化为临床可转化的抗衰老干预措施所面临的挑战进行了批判性评估。
细胞重编程有可能至少部分逆转一些衰老的关键标志。然而，有必要进行进一步研究以确定这些变化的生物学意义和持续时间，并确保细胞重编程作为一种年轻化方法的安全性。通过本综述，我们希望在有效延长健康寿命的探索中激发新的研究方向。
