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Unlocking the Fountain Of Youth

By Tom Seest

Can We Reverse Aging with Genetic Engineering?

At GettingOlderNews, we help people who want to learn more about aging and anti-aging.

Scientists have dedicated themselves to slowing or even reversing the aging process for years now. Their studies have uncovered two separate pathways through which cells age over time.
Researchers used the CRISPR gene-editing tool to extract DNA from human cells that simulate aging and diseases like Werner syndrome and Hutchinson-Gilford progeria syndrome. They identified genes whose deficiency alleviated cellular senescence and were associated with longevity.

Can We Reverse Aging with Genetic Engineering?

Can We Reverse Aging with Genetic Engineering?

What Secrets Does the Klotho Gene Hold?

The Klotho gene encodes a multifunctional regulator of calcium, phosphate, and vitamin D metabolism, and it functions as an unidentified hormone with unknown receptors. Furthermore, Klotho has also been implicated in cardiovascular diseases and cancer development; mutations of this gene result in increased aging and health decline in mice, while overexpressing Klotho extends life span and delays age-related decline.
Klotho (or Clotho), one of the Moirai or Three Fates who spins the thread of life and determines when mortals are born, how long they live, and when they die, is also the name of a gene associated with longevity and lifespan. Lifespans in all living things experience an inexorable process called cellular senescence that occurs as cells reach the end of their lifespan and no longer produce productively – leading to the accumulation of damaged cell structures, inflammation, pro-apoptotic signals, as well as loss of support from other cells.
Cellular senescence is a highly controlled response that requires activating multiple signaling pathways. As part of their response, senescent cells reduce nutrient intake while secreting various cytokines and factors that interfere with stem cell and progenitor function and promote the proliferation of other senescent cells; furthermore, these signals may even trigger further spread of cellular senescence to previously normal cells.
Multiple factors inhibit Klotho expression, such as angiotensin II and iron. Iron induces oxidative stress that suppresses transcription; however, this oxidative stress can be mitigated with the aid of chelating agents such as pyridoxine.
At Klotho gene levels, researchers have discovered a series of point mutations that decrease protein expression. One such mutation is a G to A transition in exon 2; another change affects binding between a-Klotho and FGFR1c receptors; finally, the KL-VS mutation alters homodimerization patterns of the protein, which could have an impactful change on mineral metabolism.

What Secrets Does the Klotho Gene Hold?

What Secrets Does the Klotho Gene Hold?

Can Targeting Wnt5a Reverse Aging Effects?

Wnt5a, one of the Wnt family of genes, plays an essential role in cell differentiation regulation. The gene encodes for a protein with two N-terminal domains, a C-terminal domain, and a peptide linker region; human Wnt5a’s gene can be found on Chromosome 3p14-p21 with 93% sequence similarity to mouse Wnt5a and is further translated to produce a 400kDa precursor protein which is then processed by secretase for further cleavage into mature Wnt5A/Wnt5B proteins which are then further processed further phosphorylated through different transcription factor control mechanisms.
Wnt5a peptide fragments bind to Fz2 receptors to inhibit b-catenin-dependent signaling, similar to how Wnt3a does (Supplementary Figure S12). Although in HeLaS3 cells coexpressing FLAG-Fz2 and LRP6-GFP simultaneously, Wnt5a competed with Fz2 for binding at CRDs on LRP6, but only Wnt5a bound there (Supplementary Figure S12). Furthermore, Wnt5a fragments caused the internalization of Fz2, but this was insufficient to block signaling via this route (Supplementary Figure S12).
Recent research demonstrated that CTCs from patients with prostate cancer tend to contain high concentrations of the Wnt5a gene, an essential regulator of noncanonical Wnt signaling that promotes cell proliferation and tumor progression. Notably, cancer patients who progress during treatment with an androgen receptor inhibitor often exhibit increased activation of noncanonical Wnt pathways; the inhibitor CASIN may help mitigate this effect by targeting the Cdc42-Wnt5a axis.
Previous studies have demonstrated that Wnt5a deletion leads to obesity and hypertrophy in mice fed a high-fat diet (HFD), while our current research shows this phenotype is also linked to adipose tissue fibrosis and inflammation. Our observations reveal this is caused by an activating loop between Wnt5a and TGF-b; targeting either YAP/TAZ or GSK-3 phosphatase can attenuate it pharmacologically, thus suggesting the Wnt5a-Cdc42 axis as an attractive target for anti-aging therapeutics as an early indicator of metabolic syndrome or age-related disease.

Can Targeting Wnt5a Reverse Aging Effects?

Can Targeting Wnt5a Reverse Aging Effects?

Can CRISPR Unlock the Fountain of Youth?

CRISPR is an innovative gene editing technology with the potential to revive extinct species and treat chronic illnesses. It was inspired by natural adaptations found in bacteria and other single-celled organisms’ DNA, making this tool possible. Clustered Regularly Interspaced Short Palindromic Repeats, or CRISPR for short, help cells fight off viruses by matching and cutting viral DNA that enters them. Scientists have devised a way to use CRISPR sequences in any cell to cut DNA; their system uses Cas enzymes together with guide RNA to locate target DNA in genomes before instructing Cas to cut at that specific site. CRISPR systems can also be programmed to add or replace specific sequences of DNA within a cell’s genome as needed.
Gene editing technology can be used to treat various diseases, such as cancer. Recently, scientists employed it to correct a mutation that led to hypertrophic cardiomyopathy, specifically adding synthetic genes to T cells that specialize in killing cancerous cells with immune cell killing mechanisms like T-lymphocytes armed with antibodies; this gave T cells more “claw-like proteins” that helped them identify and kill cancerous cells more efficiently than before – eventually hoping to test this approach in human clinical trials later this year.
CRISPR technology continues to find applications in medicine. For instance, researchers are exploring its use in making plants resistant to specific pests and diseases, potentially leading to higher-quality foods that thrive even under adverse conditions as well as helping farmers grow crops in smaller spaces.
CRISPR technology has also been utilized for medical research purposes, with researchers who created a CRISPR-based virus to eradicate Ebola using this tool to quickly create their vaccine within three weeks.
Scientists are employing this tool to screen for potential drug targets, recently using it to find candidates within the castration-resistant prostate cancer gene JMJD1C and others that promote or suppress cellular senescence, which contributes to aging and age-related illnesses.

Can CRISPR Unlock the Fountain of Youth?

Can CRISPR Unlock the Fountain of Youth?

How Can Yamanaka Factors Revolutionize Anti Aging?

One of the biggest obstacles in aging research is understanding exactly how stem cells transform into nerve or bone cells, but using CRISPR; scientists can study their genomes to gain more information on this transformation. This allows researchers to develop safe techniques to treat many adverse consequences associated with aging, one example being kneed: during young adults’ knee development, chondrocytes secrete collagen that forms meniscus-like tissues between bones called menisci; however, as we age, these cells become unable to produce enough force-absorbing collagen and this results in brittleness within joints – something researchers hope CRISPR will reverse.
Shinya Yamanaka and his team demonstrated in 2006 that somatic cells can be transformed into pluripotent stem cells through overexpressing four transcription factors (commonly referred to as “Yamanaka factors”): Oct3, Sox2, Klf4 and c-Myc (commonly known as OSKM genes). These reprogramming factors also play an essential role in inducing induced pluripotent stem cells from adult mouse fibroblasts.
These results have led to several studies which demonstrate how reprogramming can reverse some hallmarks of aging in mice, suggesting it may also reverse symptoms associated with human aging – although experts not involved in the work caution against premature claims of reversing it.
Researchers must first gain an understanding of epigenetic reprogramming, the process by which genes can be activated or deactivated, before looking for ways to block this process in order to extend a person’s lifespan.
Another approach involves identifying senescent cells – cells which have stopped repairing themselves or dividing – so scientists can isolate and reprogram them back to a more youthful state using Yamanaka factors. This process could enable researchers to reset our cellular clock and ensure we live longer and healthier lives as a society.
Replacing senescent cells could open up new opportunities for regenerative medicine and anti-age therapies, but its application remains experimental. Rejuvenate Bioscientists are exploring this technique and have shown it can reverse the effects of aging in mice. They plan to test this approach on people, though this process will likely be lengthy.

How Can Yamanaka Factors Revolutionize Anti Aging?

How Can Yamanaka Factors Revolutionize Anti Aging?

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