Over the past 150 years, the average human life expectancy has doubled, however, the increase in average life expectancy is actually almost entirely attributable to the use of antibiotics and vaccines, advances in public health such as clean water, and increased food production. That is to say, the increase in the average human life expectancy is actually due to the prevention of premature death. Therefore, how to slow down aging and prolong healthy life is still a very challenging topic in the field of biomedicine.
As we all know, telomeres and aging have an inseparable relationship, cells in the process of division, telomeres continue to shorten, once telomeres shortened to a certain extent, the cells will enter the aging state and die. Telomerase reverse transcriptase activates telomerase, which in turn prolongs telomeres. Animal model studies have shown that TERT has great potential for extending healthy lifespans and reversing aging.
The folliclestatin gene encodes a secreted protein expressed in almost all mammalian tissues, and in muscle, FST acts as a negative regulator of myostatin. Previous animal model experiments have shown that FST can significantly increase muscle mass and improve muscle function in older mice.
These studies all support TERT and FST as candidate targets for gene therapies that improve healthy lifespan.
Recently, Zhu Hua of Rutgers University, Elizabeth Parrish, CEO of anti-aging company BioViva, and George Church of Harvard University, as co-corresponding authors, published a research paper entitled": New intranasal and injectable gene therapy for healthy life extension in the Proceedings of the National Academy of Sciences.
The study showed that the use of cytomegalovirus as a gene delivery vector, through intranasal inhalation or injection, TERT gene therapy or FST gene therapy in mice can significantly improve healthy aging-related biomarkers, extend the life of mice by about 40%, and there are no side effects such as increasing carcinogenicity.
If this research is translated into humans in the future, it is expected to greatly alleviate the pressure and negative effects of population aging.
The study's three co-corresponding authors: Hua Zhu (left), George Church (center), and Elizabeth Parrish (right)
As the global ageing levels increase, providing diverse and effective ways to mitigate the impacts of ageing on human health is critical, both socio-economically and medically.
As more longevity-related genes are discovered, exploring high-volume gene therapy vectors that can deliver multiple genes at the same time has important prospects and significance. Unlike adeno-associated viruses, lentiviruses, or other commonly used gene therapy delivery vectors, CMV has a larger genome and a unique ability to integrate multiple genes.
In addition, CMV does not integrate its DNA into the host genome during the infection cycle, reducing the risk of insertion mutagenesis. Moreover, 90% of humans are already infected or carry CMV, and they usually have no symptoms in healthy adults. Clinical trials have also confirmed the safety of human cytomegalovirus as a gene therapy delivery vector.
Mouse CMV is very similar to human CMV, including viral pathogenesis, homology, viral protein function, viral gene expression and viral replication.
In this paper, the research team used mouse CYTOV as a delivery vector and has determined whether CMV vectors can be used as safe and effective delivery vectors for TERT gene therapy and FST gene therapy, and whether these two gene therapies are safe and effective.
In this study, they found that mouse CYTOMEcs were used as a delivery vector, administered by injection or intranasal inhalation. The experimental results showed that after the administration of these two modes of administration, the TERT and TST proteins peaked on day 7, after which it began to decline slowly, returning to its initial level on day 25. This suggests that both modes of administration can efficiently deliver and express the protein of interest in vivo.
The treatment results showed that the median lifespan of mice in the blank control group, mouse cmV intranasal inhalation control group, and mouse CMV injection control group was 26.7 months, 26.5 months, and 26.4 months, respectively. The median lifespans of mice in the TERT gene therapy group and the FST gene therapy group were 37.5 months and 35.1 months, respectively. The longest lifespan of mice in the TERT gene therapy group reached 41.2 months, and the maximum lifespan of mice in the FST gene therapy group reached 38.0 months.
That said, TERT gene therapy and FST gene therapy extended the median lifespan of mice by 41.4% and 32.5%, respectively.
The study also showed that cmV-delivered isotherapies were comparable in efficacy, whether inhaled intranasally or injected. This indicates that the expression of the gene of interest is not affected by different delivery methods resulting from different vector interactions with the immune system.
In addition to life extension, these two gene therapies have significantly improved glucose tolerance, bodily functioning, and preventing weight loss and hair loss. In addition, TERT gene therapy improved aging-related telomere shortening, and both gene therapies inhibited mitochondrial structural damage.
Both injection administration and intranasal inhalation delivery are safe and effective in delivering the same excellent gene therapy effects to multiple organs with lasting benefits, with no carcinogenic and other unwanted side effects found.
This study demonstrates that two gene therapies with CMV as delivery vectors can significantly prolong life and promote positive metabolism and bodily functions. The research team said further research could shed light on the ability and effectiveness of CMV as a delivery vector.
The research team concluded by saying that applying this research to humans is expected to have a significant impact on human quality of life and healthy longevity.
In fact, elizabeth Parrish, co-corresponding author of the paper and CEO of anti-aging company BioViva, performed both gene therapies on herself as early as September 2015 by injecting herself into TERT gene therapy and FST gene therapy delivered by adeno-associated virus (AAV), elizabeth Parrish in March 2016 He said that his white blood cell telomere length had increased from 6.71 kb before treatment to 7.33 kb, and said that this was equivalent to 20 years younger. But the reliability of this data and whether it actually contributes to life extensions has not been proven.