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Unlocking the Fountain Of Youth

By Tom Seest

Can Anti Aging Gene Therapy Turn Back the Clock?

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Scientists and the public tend to be suspicious of science that interferes with life itself, so Elizabeth Parrish, CEO of BioViva, came under heavy fire when she claimed that gene therapy had reversed her biological age.
Some have used CRISPR, an innovative DNA cutting system developed naturally by bacteria to attack viruses and to identify genes associated with aging and senescence.

Can Anti Aging Gene Therapy Turn Back the Clock?

Can Anti Aging Gene Therapy Turn Back the Clock?

Can Yamanaka Factors Reverse Aging?

As egg cells divide to create new animals, their contents undergo transformation to become embryonic stem cells capable of producing every other type of cell in the body. Scientists had long believed this transformation process to involve numerous factors; so when Shinya Yamanaka and Kazutoshi Takahashi demonstrated in 2006 that adult mouse skin cells could be reprogramed to become embryonic stem cells using four specific genes called Yamanaka factors – creating what has come to be known as Induced Pluripotent Stem Cells or iPSCs).
Yamanaka factors regulate a development signaling network that maintains pluripotency of embryonic stem cells and may induce it in differentiated cells. This network includes approximately 12 essential developmental pathways. Yamanaka factors bind to promoter regions of genes to control expression; additionally, they can repress some pathways while activating others – this indicates they possess a complex and dynamic regulatory circuit capable of self-regulation, interconnectivity, and feed-forward regulation.
Researchers have successfully used Yamanaka factors to reprogram aged fibroblasts from human donors into an immature state and observed them revert back to normal gene expression, telomere length, and mitochondrial function – supporting the idea that they can rejuvenate cells by undoing age-related defects.
Jean-Marc Lemaitre and his colleagues conducted further tests of this hypothesis by reincorporating Yamanaka factors back into iPSCs while adding two additional pluripotency genes – NANOG and LIN28 – into an “immature restorer” mixture that partially restored cells back to an immature state, then injecting this mixture into mice; animals survived longer after receiving injections from this mixture than control animals, with patterns of DNA methylation restored that were shut off by Yamanaka factors being reinstated back into these cells as well.
Rejuvenate Bio, based in San Diego, is developing an anti-aging gene therapy using Yamanaka factors in people. They injected their mixture into older mice and saw an average lifespan increase from 9 weeks in control groups to 18 weeks when injected with their mixture – partially restoring patterns of DNA methylation associated with young animals. Although results are promising, further testing in larger mammals must occur before this approach can reach clinical trials.

Can Yamanaka Factors Reverse Aging?

Can Yamanaka Factors Reverse Aging?

What Makes Sirtuin Genes the Key to Slowing Aging?

Sirtuins are a family of genes that have been shown to play an essential role in increasing animal lifespan and protecting them against age-related health conditions such as deregulated metabolism and cancer. Sirtuin genes consist of seven proteins known as histone deacetylases that require NAD+ for activation – relatively recent discoveries that have already generated much discussion due to their potential as longevity-promoting agents.
Sirtuins play an essential role in maintaining genome stability and controlling gene expression by deacetylating histone proteins and other epigenetic enzymes with their unique process known as deacetylation, also known as sirtuin-mediated deacetylation. Deacetylation ensures genome stability while simultaneously managing gene expression.
Mammalian sirtuin genes code for seven proteins with various functions, substrate affinities, and subcellular compartmentalization properties. Of these seven, SIRT6 stands out as being particularly well studied; it serves as both histone deacetylase and NAD-dependent protein kinase activity that may contribute to cell senescence and aging processes.
SIRT6 activity may encourage autophagy, the process in which cells consume their own waste products to generate energy for growth and reproduction. Autophagy helps cells stay fit by clearing away resources used for excessive growth or reproduction and freeing up resources that could otherwise be allocated toward DNA repair processes and other necessary cellular functions.
Sirtuins have many important functions. One key one is limiting oxidative stress. Additionally, they help to regulate cell cycle regulation and stop cancer cells from proliferating by activating genes associated with stress resistance, metabolism, and apoptosis. Furthermore, sirtuins promote FoxO transcription factors, which are factors associated with longevity.
The idea that protein therapies could extend human life remains controversial. While studies have demonstrated the efficacy of calorie restriction (CR) and sirtuins in prolonging yeast lifespan, other experiments have not discovered an increase in SIRT2 activity due to CR in either flies or worms; whether these differences stem from genetic or environmental causes is still uncertain.

What Makes Sirtuin Genes the Key to Slowing Aging?

What Makes Sirtuin Genes the Key to Slowing Aging?

Can Gene Editing Reverse Aging?

CRISPR is an incredible new tool that enables scientists to efficiently program and edit cellular DNA. First developed in nature by bacteria to neutralize viruses that attacked them, scientists have now adopted CRISPR for use with aging cells so they may regain their youthful structure and function more quickly while eliminating harmful genetic mutations that accelerate aging processes.
Researchers recently used a genome-wide CRISPR/Cas9 screen to identify genes that impact aging. By testing cells exhibiting disease-causing premature aging, they identified KAT7 as one such gene that promotes cell senescence; their findings indicate that inhibiting it could significantly extend human lifespan.
Researchers also demonstrated that inactivation of this gene could slow aging and extend mouse lifespan. They used an intravenously administered lentiviral vector encoding Cas9/sg-KAT7 to treat mice; the treatment reduced liver cell senescence, reduced circulation senescence-associated secretory phenotype factors (SASPs) factors and lengthened healthspan and lifespan in these animals.
This study marks a landmark in anti aging research. Scientists have long attempted to halt aging by treating its symptoms – often too late! Now, however, they’re exploring its root causes in order to prevent disease and frailty before it takes hold.
Church is working on developing a CRISPR-based system that will target single genes and make them “disappear”. This could be accomplished by altering only some of the thousands of genes within our bodies; such an approach could prove more cost effective than traditional vaccines that target whole populations and multiple genes simultaneously.
CRISPR can also be used to correct missense mutations associated with Alzheimer’s disease in proteins such as SOD1 (A272C mutation) and FUS (G1566A), using CRISPR-Cas9 successfully to do so in human fibroblasts and hiPSCs; now researchers plan to implement this technique with human iPSCs derived from patients diagnosed with AD using mitoCas9 protein that targets mitochondria DNA to correct any mutations associated with AD.

Can Gene Editing Reverse Aging?

Can Gene Editing Reverse Aging?

Can Tert Gene Therapy Reverse Aging?

Telomerase enzymes can prevent cell telomere shortening, which leads to cell senescence and eventually death, as produced naturally by stem cells that are responsible for maintaining body tissues and replacing lost cells. Studies have demonstrated that gene therapy reintroducing telomerase enzyme into cells extends lifespan in mice while simultaneously decreasing mitochondrial structure degradation and stopping cell senescence, suggesting that it could provide effective treatments against age-related diseases and slow human aging processes.
The TERT gene encodes the enzyme telomerase, which restores telomeres every time cells divide. However, this protein’s activity is controlled through several complex mechanisms and is susceptible to dysregulation during carcinogenesis and cancer progression. For instance, its promoter contains a binding site for ETS factor ETV5, which regulates transcription according to telomere length (24). A recent study of thyroid tumors concluded that three copies of TERT were associated with increased survival and an improved prognosis (21).
Rejuvenation Technologies has developed an exclusive mRNA construct for targeted delivery of human telomerase (hTERT). This non-integrative AAV vector will quickly initiate telomerase activity within cells, leading to rapid extension of telomere ends and continued cell division.
Additionally, mRNA delivery multiple times within one cell cycle without changing its phenotype ensures that telomere length remains within an acceptable range for proliferation as well as eliminating insertional mutation and off-target effects.
AAV9-Tert treatment results in increased numbers of doublecortin-positive cells in mice’s dentate gyrus and neocortex, suggesting TERT gene therapy could slow neurodegeneration as mice age. If human studies replicated, such results suggest telomerase gene therapy could prevent Alzheimer’s disease and other neurodegenerative disorders in people.
AAV9-Tert has already been proven to extend mouse lifespan by approximately 40% – this result is comparable to that of another anti-ageing compound such as rapamycin. The longevity effect is due to reduced levels of amyloid-beta and tau proteins. These results demonstrate AAV9-Tert’s potential therapeutic applications; further investigation should take place.

Can Tert Gene Therapy Reverse Aging?

Can Tert Gene Therapy Reverse Aging?

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