Cellular Fragility Syndrome May Explain Accelerated Aging In Young People

C15:0 deficiency syndrome

“The discovery of a nutritional C15:0 deficiency syndrome is the culmination of over a decade of rigorous studies,” shared Dr. Stephanie Venn-Watson, the lead author and co-founder of Seraphina Therapeutics. “As a hopeful inspiration to fellow and future scientists, this shows that there are still simple and impactful discoveries to be made that can meaningfully improve global health.”

Previously having low levels of C15:0 has been shown to increase the risk of developing heart disease, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). Around the World, levels of C15:0 have been declining. This decline is due to the avoidance of whole-fat dairy products which has been worsening with each generation. The U.S. Department of Agriculture describes this trend as “difficult to reverse” which is unfortunate because C15:0 is a stable odd-chain saturated fatty acid that is primarily found in whole dairy fat as well as some types of plants and fish. 

The study

The recent study describes how levels of C15:0 within cell membranes can result in ferroptosis (a type of cell death) which has been linked to accelerated aging, NAFLD, heart disease, and type 2 diabetes. Occurrences of these diseases have been steadily increasing, especially among younger adults, and the cause of ferroptosis was a mystery. However, in this study, Dr. Venn-Watson provides evidence to explain how nutritional C15:0 deficiencies can cause cellular fragility and ferroptosis. 

“A somewhat mysterious type of cell death, called ferroptosis, showed up as our C15:0 levels have been declining,” said Dr. Venn-Watson. “We have demonstrated not only that low C15:0 can lead to ferroptosis and its downstream complications, but that replenishing these levels directly halts all core components of this new cell killer.”

What they found

According to the researchers, increasing the level of C15:0 through diet or supplementation was found to reverse all core components of ferroptosis by stabilizing cell membranes, halting liver iron deposition, repairing mitochondria, and decreasing reactive oxygen species (ROS). C15:0 supplementation was observed to lower the levels of glucose, cholesterol, and triglycerides as well as repair liver function and improve red blood cell health in all relevant models. Based on these findings, the lack of a nutrient causes a condition, and replenishing it reverses the condition demonstrating hallmarks of a nutritional deficiency. 

Promoting longevity

Many people today will have C15:0 levels at around 0.2% of total fatty acids. Studies support maintaining circulating levels between 0.2% and 0.4% to protect against Cellular Fragility Syndrome, however, evidence suggests that higher levels can further support longevity and long-term heart health.

A study published in PLOS Medicine following over 4,000 participants for 16 years showed that those with C15:0 levels between 0.40% and 0.55% had the lowest risk of developing heart disease. 

The Blue Zone of Sardinia

Another study published in GeroScience following people living in the Blue Zone of Sardinia, Italy found that the longevity warriors had C15:0 levels three times higher than that of the general population of people living in a low longevity zone. The people in this Blue Zone tend to replace meat with cheeses made from the local mountainous grazing goats and sheep which is high in C15:0 content. 

The Blue Zone of Sardinia boasts the highest percentage of men in the World who live to be at least 100 years old, and this rate of centenarians has been attributed to fewer deaths from heart disease. C15:0 is known to promote longevity, and it has been shown to possess more cellular benefits than most leading longevity-enhancing molecules such as acarbose, rapamycin, and metformin. 

“There are two big benefits of a discovered nutritional deficiency syndrome,” shared Dr. Venn-Watson. “The first is that C15:0 can be measured to identify people who have low levels. The second is that we can drive meaningful changes in our diets and global nutritional guidelines to help replenish population-wide C15:0 levels and fix these deficiencies.”

Accompanying video: https://www.youtube.com/watch?v=k1yRoeAeI68&t=2s