Longevity Daily: 13th 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. According to Cancer Research UK, and the American Cancer Society one in two people will develop cancer at some point in their lives. Indeed cancer is one the most devastating diseases of aging. Now, there may be some good news as well, especially pertaining to lung cancer.
   • Lung cancer is by far the leading cause of cancer death among both men and women, making up almost 25% of all cancer deaths in the US, and globally it is even higher
   • According to a study published today by researchers at the National Cancer Institute mortality rates from the most common lung cancer, non-small cell lung cancer (NSCLC), have fallen sharply in the United States in recent years, due primarily to recent advances in treatment.
   • The researchers found that, in recent years, deaths from NSCLC decreased even faster than the decrease in NSCLC incidence (mainly due to reduction in smoking), and the decrease in deaths was associated with a substantial improvement in survival.
   • NSCLC accounts for 76% of lung cancer in the U.S., and in the last decade new treatments for NSCLC have become available, including those that target genetic changes seen in some NSCLC tumors as well as immune checkpoint inhibitors that help the immune system better attack NSCLC.
   • The researchers note that the accelerating decline in NSCLC mortality that began in 2013 corresponds with the time when clinicians began routinely testing patients for genetic alterations targeted by newly approved drugs.
     
     
2. Historically, frailty has been synonymous with old age. Up until the 1970s when older patients would die in hospital setting in many cases doctors would write ‘frailty’ as their cause of death. Today we understand that frailty is caused due to biological ageing, and stems from imbalance in multiple biological pathways. Frailty is associated with low energy levels, and it increases risk of suffering from disabilities.
   • In this paper researchers, and clinicians from Albert Einstein College of Medicine in New York tried to assess how the process of biological aging causes frailty, and if there is a way we can predict it.
   • They analyzed the proteins in blood plasma from a total of 880 individuals; 448 were offspring of parents with usual survival (OPUS) and 432 were offspring of parents with exceptional longevity (OPEL).
   • The study identified a number of proteins that were positively as well as negatively associated with frailty. The proteins positively associated with frailty are FABP, FABPA, and leptin, and these pointed towards lipid metabolism playing a major role in frailty.
   • The top most protein negatively associated with frailty was ANTR2 (anthrax toxin receptor protein 2), also called capillary morphogenesis gene 2 (CMG2), which is characterized by its binding ability to anthrax toxin. It is involved in creation of new blood vessels, and collagen assembly in the connective tissue.
     
     
3. Alpha-synuclein is a protein of unknown function that accumulates in certain neurodegenerative diseases, the most well known being Parkinson’s disease. As exercise appears to protect the brain against Parkinson’s disease, researchers in this study asked whether exercise could affect the epigenetic regulation the gene that encodes alpha-synuclein.
   • They studied methylation, a form of epigenetic modification that can modify gene expression. They found that in the blood, methylation of a specific region of the alpha-synuclein gene increased with age.
   • Physical exercise was associated with lower total and oligomeric alpha synuclein levels in the blood, but did not affect methylation status.
   • Exercise did, however, affect levels of methylation enzymes, and it is possible that other epigenetic mechanisms for the regulation of α-synuclein expression may exist.
     
     
4. We usually associate genetic mutations with negative effects, but the situation is not as simple as it may appear. Laron syndrome is a disorder caused by insensitivity to growth hormones and it’s symptoms include dwarfism, seizures, truncal obesity and sometimes decreased intellectual capacity. However, people affected by this syndrome have resistance to cancer and diabetes type 2, which shows the importance of signalling pathways induced by growth hormone in the proliferation of cancer.
   • Scientists have studied pathway affected by Laron syndrome and have found that mice with growth hormone receptor deficiency exhibit reduced cancer incidence, which can be associated with lower mutation frequency in various tissues
   • Also, it is interesting to see that the lifespan of people affected by Laron syndrome is similar to unaffected people, however, 70% of death causes aren’t age-related and there is a notable lack of cancer mortality.
     
     
5. Telomeres are short nucleotide sequences which cap chromosomal strands, protecting the DNA from degradation. Much like the little plastic bit on the end of your shoelace, telomeres are there to stop the DNA strand from unravelling. Telomere shortening has been heavily associated with ageing and age-related diseases.
   • A meta-analysis, carried out in 2017, including 16,000 participants and spanning 27 different studies, found that there is a significant association between adverse childhood events (ACEs) and telomere length.
   • A study published just 3 days ago looked to test this association as well as observing the mechanism of action underlying these associations.
   • A small, but significant association of ACEs with telomere length was found, with every ACE resulting in a 1% decrease in telomere length.
   • Self-control of the individual was found to mediate the association between ACEs and telomere length, which may prove to be the first stepping stone on the pathway identifying the relationship between ACEs, telomere length and wider health implications.