Newsletter #216 - How Spermidine Fights Aging 🥦🍞
Hey friends! This week, I decided to take a look at some of the research on dietary polyamines, because we really don't talk about them much but they seem to be pretty awesome. Polyamines are organic compounds that play a wide range of important physiological roles within the body. They are also found in plants, where they perform similarly vital functions, and consuming plants that contain these polyamines has been shown to be associated with an array of health benefits.
The most interesting polyamine, from a nutritional standpoint, is spermidine. Spermidine, as the name not-so-subtly suggests, was originally isolated from sperm but it has since been identified in a wide range of plant-based foods.
Spermidine has been identified as a potential caloric restriction mimetic, meaning that it activates some of the same molecular pathways (and perhaps, the same metabolic effects) that are associated with fasting and calorie-restricted diets. The primary molecular mechanism seems to be through helping to induce protective autophagy, which is the process through which cells clean up damaged proteins and organelles. As we age, autophagy tends to decline, which in turn leads to deterioration in cellular and tissue function, so there is immense interest in finding ways to regulate this process. This is particularly true with respect to mitochondrial autophagy, or mitophagy, since mitochondria generate the energy that we need for various chemical processes.
This Week's Research Highlights
🌱 Spermidine is associated with reduced mortality from any cause.
A number of studies animal models have shown that spermidine prolongs lifespan and seems to prevent the onset of age-related disease. Specifically, mice that consume a diet supplemented with spermidine show an increase in longevity of up to 25% which is pretty darn impressive. But how does that translate to people? To see how spermidine content in the diet associates with mortality in humans, researchers analyzed data from an Italian cohort living in South Tyrol. Diet was assessed through repeated food frequency questionnaires, and the subjects were followed for about 20 years. Out of 146 different nutrients that were studied here, spermidine showed the strongest statistical impact on all-cause mortality. Compared to those in the bottom third of spermidine intake, those in the highest tertile of intake had a ~39% lower risk of dying from any cause over the course of the study, after adjusting for various potential confounders, including indexes of a healthy diet. According to the researchers, the difference in mortality between the top and bottom thirds of spermidine intake was tantamount to a 5.7 year difference in chronological age.
🫀 Spermidine may improve cardiovascular function and decrease risk of CVD mortality.
Cardiovascular disease tends to accompany aging for a few different reasons. Alterations in the structure and function of the heart itself play a major role. As the heart ages, the wall of the left ventricle tends to get thicker, and the tissue becomes stiffer, making it harder for the ventricles to fill completely and leading to all kinds of problems. To explore how spermidine could affect age-related hypertrophy and diastolic dysfunction, researchers took groups of mice and fed some of them water with spermidine added in as a supplement, while others just got plain water (controls). Those that were fed spermidine had significantly longer median lifespans than controls, even when they weren’t administered the spermidine until relatively late in their lives. When the researchers examined the cardiac tissue of the elderly rodents, they observed that spermidine had reversed age-associated remodeling of their hearts, to the point of more closely resembling the organs of middle-aged mice. When they zoomed in even closer and analyzed the individual heart cells, they found that spermidine appeared to have promoted mitophagy in these cells (leading to more and better functioning mitochondria), and reversed age-induced decline in mitochondrial respiratory function. Finally, to see how this might play out in humans, the researchers took a look at dietary data from the South Tyrol cohort cited in the previous study, and noticed that those in the highest spermidine intake group had a 40% lower risk of fatal heart failure, as well as lower risk of other cardiovascular diseases.
🧠 Spermidine may improve cognitive function and reduce risk of cognitive impairment.
Along with other parts of the body, aging generally leads to a progressive deterioration of memory and other cognitive functions. This has been linked at least in part to mitochondrial dysfunction. Neuronal mitochondria are dynamic organelles that are constantly dividing and fusing inside their cells. Over time, they get chunkier due to repeated fusion, and gradually lose functionality due to a failure of mitochondrial quality control. Restoration of autophagy, in theory, should target these damaged mitochondria and replace them with functional components, thus improving cellular health and brain performance. To test whether spermidine could help with that, researchers performed a series of experiments in animal models administering spermidine. They found that giving spermidine to older mice for six months resulted in improvements in spatial learning tasks. When they examined the brains of these rodents, they found that spermidine had crossed the blood-brain barrier and was detectable in brain tissue after just a week of supplementation. When the researchers then examined a fruit fly aging model, they found that spermidine supplementation boosted mitochondrial respiration in neuronal tissues, and this effect was proven to be dependent on mitophagy (fruit flies with mutations that interfere with mitophagy did not show improvements in mitochondrial function or in cognition in response to spermidine) Then, much like the previous two studies, these researchers looked at the South Tyrol data, but this time examining the cognitive function of these participants. Sure enough, higher spermidine intake was associated with lower risk of cognitive impairment in a dose-dependent manner.
Random Trivia & Weird New
🔬 In 1846, Pennsylvania scientist Joseph Leidy was the first person to solve a murder mystery using microscopy.
A murder suspect in Philadelphia was found to have blood on his clothes and hatchet, which he claimed was from chickens that he had been slaughtering at the time of the crime.
Leidy, then working under the coroner of Philadelphia, examined the blood with his microscope and observed that the blood cells did not have nuclei. Why is this such a big giveaway? Well, the red blood cells of birds do contain nuclei, suggesting that this could not possibly be chicken blood, as the suspect had claimed. Human blood, however, is anucleate (likely because the absence of a nucleus leaves more room for oxygen-carrying hemoglobin). Having been exposed, the accused subsequently confessed.
Interesting example of how the advancement of science and technology influences so many aspects of human civilization. In another era, before the development of the light microscope, perhaps this guy would have gotten away with his crime?
Podcasts We Loved This Week
- Danny Lennon and Alan Flanagan: Are vegetables detrimental to health? Via Sigma Nutrition Radio.
- Eric Rawson: Creatine for brain health and physical performance. Via The Proof Podcast.
Products We Are Enjoying
Most people get the bulk of their dietary spermidine from cereals, legumes, and soy products. However, cruciferous vegetables are also a very good source. And young versions of these vegetables (meaning sprouts and microgreens) may be particularly rich in these compounds, because polyamines play a key role in growth and development of germinating plants (probably a major reason it was originally found in sperm now that I think about it).
I did some digging out of curiosity, and noticed that one analysis found that daikon radish sprouts contained 423 mg/kg of spermidine, which would place it right up there at the top among the best sources in the diet.
I decided to try sprouting them, and was pleasantly surprised at the results. It’s insanely easy to do: just stick them in a mason jar with a mesh lid at an angle and rinse them 3-4 times daily, and you’ll have beautiful sprouts before the end of the week. Very hard to mess up - definitely more forgiving than broccoli sprouts. They do have an interesting spicy taste that takes some getting used to, but they’re quite palatable when mixed in soups and salads.
humanOS Catalog Feature of the Week
How-to Guide - Mediterranean Diet
When we talk about the Mediterranean diet and what makes it healthy, we usually think of olive oil, red wine, and some other hallmarks of Greek/Italian cuisine. Interestingly, it has also been suggested that polyamines may also play a role in this association. The traditional Mediterranean diet happens to be quite rich in spermidine, containing 2-3 times as much as the standard American diet, and as the research described above suggests, spermidine seems to be pretty good for you.
In this reference sheet, we go over the fundamental principles of the Mediterranean diet, what components of the diet make it healthy, and what sorts of foods and beverages you should consume in order to achieve the best possible version of this dietary pattern based on the current scientific literature. Great if you’re looking for a basic, efficient guide to how to Mediterraneanize your eating habits. For a little bit of a deeper dive, you can refer to our Mediterranean Program, which delves into the background of the Mediterranean diet as well as the clinical research.
Thanks for reading, enjoy the weekend, and we'll see y'all next week!