Senescence - also called cellular degeneration, is considered the trademark for aging. As we get older, genes that maintain cellular health and vitality are down-regulated.
At the same time, genes that promote disease and senescence become over-expressed. This brings in a multitude of illnesses:
cardiovascular diseases, cancer, and neurodegenerative disorders like Alzheimer's, among others.
Nowadays, promising life extension technologies are being investigated, with potential for preventing many diseases, adding decades to the human life span, and restoring youthful function to an aging body. Gene therapy - the therapeutic delivery of genes to treat or prevent disease - is one of them.
Gene therapy is designed to introduce genetic material into cells to compensate for abnormal genes or to make a beneficial protein. If a mutated gene causes a necessary protein to be faulty or missing, gene therapy may be able to introduce a normal copy of the gene to restore the function of the protein. Moreover, the genome function could be reprogrammed through this unique technology, in an attempt to prevent/limit disease and senescence. A gene cannot be inserted directly into a cell. Instead, a carrier called a vector is genetically engineered to successfully deliver the gene. The vector can be injected directly into a specific tissue in the body, where it is taken up by individual cells .
The first attempt at modifying human genome was performed in 1980 by Martin Cline, however the first successful nuclear gene transfer in humans, approved by the National Institutes of Health (NIH), was performed in 1989. Up until present, over 2300 clinical trials have been conducted and the number is expected to significantly grow in the future .
One of the biggest discoveries in the field of gene therapy, was attributed to the Japanese researcher Shinya Yamanaka - awarded with the Nobel Prize in 2012. He identified four genes, which he called the "Yamanaka factors", that, when triggered, could convert any adult cell into induced pluripotent stem cells (iPSCs). The method, called cellular reprogramming, was a breakthrough because iPSCs can divide indefinitely and become any cell type. That means they behave like embryonic stem cells. In 2016, scientists at the Salk Institute were able to turn back "the cellular clock" by triggering, through gene therapy, the "Yamanaka factors". They found that applying this "cellular reprogramming" for brief periods of time not only rejuvenated human cells in a petri dish, but it also reversed the effects of aging in live mice with progeria - a rare genetic disease that causes adolescent mice and human children to age rapidly. They were able to regenerate damaged tissues and organs in the progeria-affected animals and extended their lifespan by 30% . Activating the Yamanaka factors triggers rapid cell division - beneficial in growing embryos and cellular regeneration - however it has the downside of promoting tumor growth. In fact, when the Salk Institute team gave the mice the treatment continually, some developed tumors and died. The good news is that they eventually found a sweet spot: treating the mice two days a week led to significant health benefits with no indication of tumor development. Taking into consideration the positive results, the team is optimistic about starting human trials soon .
Another cutting-edge genome editing technique, called CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats), enabled scientists to precisely program or "edit" DNA genes. CRISPR offers a new way to rapidly transform senescent cells to regain youthful function and structure, possibly allowing youthful health to be systemically restored. CRISPR was originally developed in nature by bacteria as a way to destroy the DNA of viruses that frequently attack them. This served as a model and scientists adapted the natural version of CRISPR in order to enable the reprogramming of cellular DNA to get rid of unfavorable genetic changes. Dr. George Church - a pioneer in the area of genome engineering and development of gene editing tools - has already been able to reverse aging in human cells using CRISPR technology, and expects the first clinical trials of this technology for anti-age purpose to begin within as little as one year . CRISPR has already been tested in humans, as a potential way to cure non-small cell lung cancer, and several other trials are expected in 2017 [6,7]. As key features of aging are powerfully controlled by how genes are activated or inactivated in the body, CRISPR technology is a critically important breakthrough in the fields of genetics and age-reversal.
In 2017, promising anti-aging results have been shown by a study of the compound Astaxanthin by researchers at the University of Hawaii, in partnership with the life sciences company Cardax Inc. The Astaxanthin compound CDX-085, developed by Cardax, showed the ability to significantly increase the expression of the FOXO3 gene, which was previously proved to play a key role in longevity. A nearly 90% increase in the activation of the so-called "longevity gene" was observed in the mice fed with CDX-085. Vassilis L. Syrmos, the vice-president of Cardax, declared that this study proves that very promising results that may help mitigate the effects of aging in humans can be achieved in the future .
In his best-seller book, The Selfish Gene, Richard Dawkins describes an interesting approach to life-extension - "fooling genes" into thinking the body is younger. Dawkins attributes inspiration for this idea to Sir Peter Medawar, a British biologist whose theory about senescence served as the basis for all modern theories for the evolution of senescence and aging. Our bodies are composed of genes that activate at different times throughout our lifetimes - some when we are young and others when we are older. According to Dawkins' theory, these genes are activated by environmental factors, and the changes caused by the activation of these genes can be lethal. It is a statistical certainty that as we grow older, we possess more lethal genes than in early life. Therefore, to extend life, a potential strategy would be to prevent these genes from switching on. As to how this can be achieved in the future, the biologist strongly believes that we should start by "identifying changes in the internal chemical environment of a body that take place during aging... and by simulating the superficial chemical properties of a young body" .
Millions of dollars have been invested in finding a cure for the age-related degeneration that has traditionally been thought of as inevitable. Now, it's finally yielded results, and gene therapy is one of the most promising. There are still some challenges that researchers must overcome before it will be a practical approach to treating disease, such as targeting genes to specific cells, to avoid potential side effects and ensuring that the new genes are precisely controlled by the body. However, scientists are confident that with the aid of today's technology we will be able to successfully overcome those challenges soon.
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