Longevity Daily: 31st 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. Can eating a bit less increase our lifespan, and improve our health?
   • Why is this important: Since 1935, many laboratory studies in animals have show that restricting the number of calories in an animal’s daily diet can improve their health and in many cases help them live longer lives. Although calorie restriction has been shown to extend the lifespan of a wide variety of animals such as yeast, flies, worms, mice, and rats, it has been hard to study calorie restrictions benefits in humans.
   • What did the researchers do: In a seminal study called the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE), the US National Institutes of Health recruited 34 people to reduce their overall calorie intake by 15% for 2 years. The CALERIE study also recruited 19 control subject who could eat as they normally would. The study collected weekly blood, bone, urine, internal body temperature, and from time to time study participant spent 24 hrs in metabolic chamber to measure their metabolic rates.
   • Key takeaway(s): After 2 years, the calorie restricted people lost average of 8.7 kgs (19.18 lbs) in weight, while the non-calorie restricted people gained about 1.8 kgs (~4 lbs). The study also showed that the calorie restricted people reduced their metabolic rate by 80 to 120 Calories per day. The researchers hypothesized that longterm slower metabolism could lead to improved health, and longevity via reduction in inflammation, and reduced damage from free-radicals.
     
     
2. What is the fast(est) way to improve our health and live long?
   • Why is this important: From the study mentioned above we learnt that we can lose weight, and become healthier by eat 15% less for two or more years. But most of us do not have the will power, or patience to keep up our calorie restricted diet for years. Is there a faster way to gain all the benefits of calorie restriction?
   • What did the researchers do: Researchers from Italy, Germany and the US studied 71 participants for about 2 years on a fasting mimicking diet. The participants did only 5 consecutive days of fasting mimicking diet each month for 3 months, and the rest of the time they ate normally. The fasting mimicking diet provided between 700 to 1000 Calories per day, and all the necessary vitamins, macro- and micronutrients.
   • Key takeaway(s): The researchers found right after completing three-months of just 5-day fasting mimicking diets the participants lost weight, reduced fat, lowered their blood pressure, and decreased harmful growth factors in their blood. A longer term analysis of these participants showed that just by doing a few 5-day fasting mimicking diets a years people might be able to lose weight, reducing their blood pressure, reduce their blood sugar levels, reduce their cholesterol levels, and reduce their markers for harmful inflammation.
     
     
3. Can microbes in the gut contribute to brain aging?
   • Why is this important: We know that cognitive decline during aging is partly caused by increased inflammation in the brain. We also know that bacteria in the gut can have a profound effect on both the immune system and the central nervous system. The gut microbiome may therefore modulate cognitive decline.
   • What did the researchers do: Here, researchers investigated the role a molecule produced by gut microbes, called trimethylamine N-oxide (TMAO), in modulating inflammation and cognitive function in the aging brain.
   • Key takeaway(s): In humans, higher levels of TMAO correlated with poorer cognitive performance. In mice, TMAO levels increased with age and were associated with higher brain inflammation, and mice that were given TMAO in their food had more inflammation and poorer cognitive function. The study suggests TMAO might be a promising target for preventing cognitive decline.
     
     
4. CRISPR gene therapy prevents obesity and metabolic syndrome caused by a high calorie diet in mice
   • Why is this important: In adults, adipose tissue consists largely of regular white adipose tissue (WAT), which is adept at storing calories. It is the expansion of these WAT cells, due to a high calorie diet, which is one of the causes of obesity, type 2 diabetes and high blood pressure, otherwise known as metabolic syndrome. Unlike WAT, mitochondria-packed, brown adipose tissue (BAT) burns more energy, meaning less calories are hoarded, and the risk of obesity, and therefore metabolic syndrome, is reduced. Finding a way to convert WAT to express a metabolic phenotype more closely resembling BAT would be a very promising way in which to battle obesity and metabolic disease. This is exactly what this study aimed to do.
   • What did the researchers do: Researchers utilised CRISPR-Cas9 gene editing technology to engineer the WAT of mice to over-express uncoupling protein 1 (UCP1). UCP1 plays a major role in the metabolic phenotype of brown adipose tissue. Genetically engineering WAT cells to over-express UCP1 results in WAT acquiring the thermogenic characteristics of BAT.
   • Key takeaway(s): Obese mice which received this treatment presented improvements in glucose tolerance, insulin sensitivity and increased energy expenditure. This data shows promising evidence for the CRISPR-engineered cell therapy being a potential therapy to combat obesity and metabolic syndrome.

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