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Longevity Daily: 21st August, 2020

Posted on 21 August 2020

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Everyday our team of researchers in Oxford are inundated with scientific, and medical research articles that have the potential to improve health, wellbeing, and longevity. In this blog we highlight a few of them that caught our attention today.

Methylmalonic acid (MMA) and cancer. MMA is produced during digestion of proteins and fats. Gomes et al.2 report that levels of MMA are elevated in the blood of people over the age of 60, compared with those under 30. The group provides evidence that large lipid structures help MMA to enter cancer cells from older blood vessels. Through unknown pathways, MMA promotes expression of the proteins TGF-β2 and SOX4. In turn, SOX4 drives global gene-expression changes that enable cells to take on the characteristics of metastatic cells, which spread cancer around the body.
  1. Why does the risk of cancer increase as we age?
  2. Can our gut microbiome impact our cancer treatment outcomes?
    • Key takeaway(s): During the study the researchers were able to identify changes in the microbiome over time in kidney cancer patients receiving immunotherapy treatment. They found that the patients who had the greatest variety of gut microorganism were more likely to receive benefit from their cancer immunotherapy treatment. The researchers think that this finding may encourage cancer doctors to prescribe foods that increase patient’s gut microbiome variety, such as high-fiber diet, and vegetables rich in complex carbohydrates.

  3. Telomerase gene therapy successful as treatment for idiopathic pulmonary fibrosis (IPF), in mice
    • Why is this important: IPF is a disease that results in the scarring of lung tissue, damaging the ability of victims to breathe. IPF affects almost 3 million people globally, with a median time from diagnosis to death as 2-4 years. The biggest factor in IPF is age.
    • What did the researchers do: Mice were treated with AAV9-Tert, telomerase activation gene therapy, or a control injection, to determine if the gene therapy is an effective treatment for IPF. The researchers found that mice treated with AAV9-Tert showed significantly increased levels of ATII and club cells, indicating rejuvenation of the lung tissue. Biomarkers for DNA damage, senescence and the impairment of surfactant activity were also decreased in mice with the gene therapy.
    • Key takeaway(s): This study demonstrates that telomerase activation gene therapy effectively prevents the degeneration of lung tissue associated with physiological ageing in mice. This furthers our understanding of the interaction of telomere length with disease, and reinforces the case for TERT as a potential therapeutic target for IPF in the future.

  4. A novel biomarker of MMP-cleaved prolargin is elevated in patients with psoriatic arthritis
    • Why is this important: Psoriatic arthritis is a long-term inflammatory arthritis that occurs in people affected by the autoimmune disease psoriasis. The exact causes are still unknown, but a number of genetic associations have been identified and no specific diagnostic test is available for confirming the malady. Psoriatic arthritis gets significantly worse with time, but early intervention and treatment can slow down the disease onset and bone damage.
    • What did the researchers do: In this study, they produced monoclonal antibodies to conduct novel ELISA test detecting a MMP-generated prolargin fragment
    • Key takeaway(s): Novel assay was robust and specific to a target sequence.
      The prolargin fragment was present in blood serum and plasma
      The fragment was upregulated in patients affected by psoriatic arthritis compared to a control group

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