Longevity Daily: 25th 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. The Impact of Our Genetics on Our Frailty, and Our Longevity
   • Why is this important: Historically, frailty has been synonymous with old age. Until recently many doctors would report frailty as a cause of death for most elderly patients. Today we understand that frailty is caused due to the process of biological ageing, and stems from dysfunction in multiple biological pathways. Frailty is associated with low energy levels, and it increases risk of suffering from disabilities. By delaying frailty we could increase our healthspan, which is defined as the years of life free from disability and disease.
   • What did the researchers do: In this review paper researchers from Albert Einstein College of Medicine, in New York assessed the biological processes associated with aging which cause frailty. They also compared this degenerative process with the protection provided to long-lived individuals (100 years or older) mainly due to their genetic inheritance.
   • Key takeaway(s): The researchers found 2 genes, APOE and FOXO3, that were consistently associated with longevity. APOE has been implicated in providing protection from Alzheimer’s disease, and cardiovascular diseases. While FOXO3 is known for its role in sensing insulin, and regulating growth. Across multiple studies the researchers found that people with a higher risk of frailty have dysfunctional genes and genetic loci associated with inflammation, cholesterol transport, and programmed cell death.
     
     
2. Can Improving Our Oral Health Improve Our Longevity, and Avoid Frailty?
   • Why is this important: In the previous post we learnt that frailty is caused due to the degenerative biological process of aging, and it significantly increases our risk of suffering from disabilities. For those of us who are not lucky enough to be born with longevity promoting genes how do we prevent becoming frail?
   • What did the researchers do: In this review paper researchers from Japan analysed the relationship between oral health and frailty, and its impact on longevity. Previous studies have shown that decline in oral health is accompanied by decline in mental and physical function, but these studies didn’t present a quantitative relationship.
   • Key takeaway(s): The researchers showed a clear relationship between the number of teeths, dentures, oral function, and gum disorder with frailty and longevity. Decreased overall oral function is an important risk factor for malnutrition, and significant loss of muscle. The researchers suggest that to prevent frailty, and improve longevity with not only need to ensure that older people have most of their teeth, but that they also have all other aspects of oral health.
     
     
3. Does non-coding genetic material contribute to Alzheimer’s disease?
   • Why is this important: Non-coding RNAs are templates produced from DNA that are not translated into proteins. Once thought of as ‘junk’, some small non-coding RNAs appear to be important regulators of complex biological processes, including aging. It has been hypothesised that alterations in these molecules could play a role in age related neurodegenerative diseases such as Alzheimer’s, but this has yet to be confirmed.
   • What did the researchers do: Researchers in this study analysed small RNAs in the brains of deceased Alzheimer’s patients and compared them with normal controls.
   • Key takeaway(s): Small non-coding RNAs are altered in Alzheimer’s disease relative to controls. Most of the alterations found were present in both Alzheimer’s disease and Alzheimers with vascular dementia. The researchers therefore suggest that small non-coding RNAs may be linked to the pathology of Alzheimer’s disease.
     
     
4. What are senolytic/senotherapeutic drugs and why are they important in aging?
   • Why is this important: As we age, our cells are becoming senescent as well, which creates a burden on organs, contributing to age-related diseases. News class of drugs, called senolytics, were demonstrated to prolong healthspan and improve stem cell function in rodents. However, there aren’t a lot of them and new screening techniques for their identification are required.
   • What did the researchers do: In this article, researchers developed a screening platform to rapidly identify drugs that target senescent cells. The platform is based on Ercc1 −/− murine embryonic fibroblasts with reduced DNA repair capacity, which means that cells ‘age’ at much faster rate.
   • Key takeaway(s): The platform was effective in screening a small library of drugs, which led to the identification of two inhibitors of HSP90 chaperone family, that have a senolytic activity in mouse and human cells.

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