Department of Microbiology, Biochemistry, and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ 07103.
BioViva USA, Inc., Bainbridge Island, WA 98110.
Proc Natl Acad Sci U S A. 2022 May 17;119(20):e2121499119. doi: 10.1073/pnas.2121499119. Epub 2022 May 10.
As the global elderly population grows, it is socioeconomically and medically critical to provide diverse and effective means of mitigating the impact of aging on human health. Previous studies showed that the adeno-associated virus (AAV) vector induced overexpression of certain proteins, which can suppress or reverse the effects of aging in animal models. In our study, we sought to determine whether the high-capacity cytomegalovirus vector (CMV) can be an effective and safe gene delivery method for two such protective factors: telomerase reverse transcriptase (TERT) and follistatin (FST). We found that the mouse cytomegalovirus (MCMV) carrying exogenous TERT or FST (MCMVTERT or MCMVFST) extended median lifespan by 41.4% and 32.5%, respectively. We report CMV being used successfully as both an intranasal and injectable gene therapy system to extend longevity. Specifically, this treatment significantly improved glucose tolerance, physical performance, as well as preventing body mass loss and alopecia. Further, telomere shortening associated with aging was ameliorated by TERT and mitochondrial structure deterioration was halted in both treatments. Intranasal and injectable preparations performed equally well in safely and efficiently delivering gene therapy to multiple organs, with long-lasting benefits and without carcinogenicity or unwanted side effects. Translating this research to humans could have significant benefits associated with quality of life and an increased health span.
随着全球老年人口的增长,提供多样化且有效的方法来减轻衰老对人类健康的影响在社会经济和医学上都至关重要。先前的研究表明,腺相关病毒 (AAV) 载体诱导某些蛋白质的过表达,可以在动物模型中抑制或逆转衰老的影响。在我们的研究中,我们试图确定大容量巨细胞病毒载体 (CMV) 是否可以成为两种保护因子:端粒酶逆转录酶 (TERT) 和卵泡抑素 (FST) 的有效且安全的基因传递方法。我们发现,携带外源性 TERT 或 FST 的小鼠巨细胞病毒 (MCMV) 分别将中位寿命延长了 41.4%和 32.5%。我们报告称,CMV 成功用作鼻内和注射基因治疗系统以延长寿命。具体而言,这种治疗方法显著改善了葡萄糖耐量、身体表现,以及防止体重减轻和脱发。此外,TERT 改善了与衰老相关的端粒缩短,两种治疗都阻止了线粒体结构恶化。鼻内和注射制剂在安全有效地将基因治疗递送至多个器官方面同样有效,具有持久的益处,且没有致癌性或不良副作用。将这项研究转化为人类可能会带来与生活质量和健康寿命增加相关的重大益处。