Longevity Daily: 18th August, 2020

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.

1. DNA damage is a major hallmark of aging which ultimately leads to cell and tissue damage resulting in diseases of aging, including cancer. We incur more than 100,000 DNA damaging events daily when we stay out in the sun too long, or smoke, or due to pollution, etc.
   • Our cells have a family of enzymes known as DNA polymerases that ensure that our DNA is copied without error during cell division, but over a long period of time things can go wrong.
   • For the first time in the world, using cryo-electron microscopy researchers from the Mount Sinai School of Medicine have been able to image the three-dimensional structure and mechanism of DNA polymerase ζ (zeta) enzyme that protects cells from constant DNA damage.
   • Knowing the three dimensional structure of this key error-checking enzyme will help us develop drugs that can help clean up DNA damage in functional cells.
   • In addition, drugs can be designed to inhibit the DNA polymerase when treating cancers like lung, prostate, and ovarian that often become resistant to chemotherapy after early use in patients.
     
     
2. Along with DNA damage, stem cell exhaustion is another major hallmark of aging. Hematopoietic stem cells (HSCs) are especially important as they are the stem cells that give rise to blood cells. We need to understand what changes occur in them during aging, and be able to detect detrimental changes early.
   • In a recent yet-to-be-peer-reviewed paper researchers from the Netherlands analyzed the active genes in HSCs from mice from various age groups, to understand and map the changes during aging.
   • They found that as mice age their HSCs have overactive regions in their genomes largely consisting of genes involved in cell membrane function, and cell surface molecules.
   • The researchers also identified a gene called Selectin P (SELP) as a marker that can predict the declining functions of HSCs, and this gene can also be used differentiate between old and young HSCs
   • Finally, the researchers show that certain types of drugs that activate our sympathetic nervous system, known as sympathomimetics, can rejuvenate aged HSCs.
     
     
3. Heart disease is one of the largest causes of age-related mortality, and ageing blood vessels are a major driver of heart disease. With age, blood vessels become stiffer and narrower, putting increasing strain on the heart. However, we don’t fully understand the molecular changes that underpin blood vessel aging.
   • In this study, researchers used RNA sequencing to compare gene expression in young and old mouse aortae.
   • Most of the upregulated pathways in old aortae related to immune response, while the most down-regulated pathways involved organisation of the extracellular matrix (ECM), the scaffold that holds cells together.
   • Control of protein folding and stress response pathways were also impaired in aged vessels.
     
     
4. Centenarians are those who live to the longevity milestone of 100 years or more, and are a group which is becoming ever more populated, with advances in biomedical areas of research. However, this cannot be said for the supercentenarians (those who live to 110 years of age). Still only 1 in every 100 centenarians become a super. As if to add insult to injury to the rest of the comparatively rapidly degenerating general population, this elite bunch tend to make it past 100 with a figurative hop, skip and a jump; maintaining reasonable cognitive function and physical ability.
   • A team at the Centre for Supercentenarian Medical Research at Keio University Medical School, in Tokyo, Japan, set out to identify biomarkers associated with exceptional survival to the supercentenarian ages.
   • A major strength of the study was the uniqueness of the cohort. A nation-wide marketing phase recruited 1,427 of the oldest people, including >600 105 year olds and 36 supercentenarians. This is the largest cohort of 105+ year olds to ever be assembled.
   • The most remarkable finding was that “low NT-proBNP levels are statistically associated with a survival advantage to supercentenarian age”. Prof. Arai, one of leaders of the study, suggested that NT-proBNP may be a surrogate marker for hemodynamic stress accompanied with ageing of the cardiovascular and renal systems, and that further investigating this molecular pathway could lead to therapeutic potential.
   • The team also found that the cardiovascular disease-related biomarkers: NT-proBNP, interleukin-6, cystatin C and cholinesterase, were all associated with all-cause mortality.