Dietary Spermidine Boosts Cognition in Bugs and Rodents

F.The supply of the organic compound spermidine to mice and fruit flies increased the mitochondrial activity in the brain of the animals and thus their cognitive abilities. This is evident from an article in Cell Reports published April 13th on People.

“Overall, I think spermidine is probably one of the most promising molecules for research on aging in general. . . and here they focus on recognition, ”says Valter Longo, gerontologist of the University of Southern California, who was not involved in the work. The most compelling data come from flies and mice, he says, because the human data is only correlative. But he adds, “The good news is that a diet high in spermidine seems like a good one. It sure isn’t bad for you ”in terms of realization.

Spermidine is a natural compound found in a wide variety of foods such as wheat germ and aged cheese, although it was originally identified in semen. The compound promotes autophagy – a type of cellular self-cleaning process – and both spermidine and autophagy levels appear to decrease in the body’s cells as animals, including humans, age.

Previous studies in laboratory animals have shown all possible benefits of spermidine, from increasing life expectancy, to fortifying heart and immune cells, to preserving memory as we age.

“Other groups have studied the effects of spermidine injections. . . about behavioral and cognitive phenotypes, but we wanted to improve translatability for future applications, so we focused on a nutritional approach, ”study co-authors Frank Madeo and Stephan Sigrist write in an email to The Scientist. Both Madeo, who studies aging at the University of Graz in Austria, and Sigrist, a neuroscientist at the Free University in Germany, are involved in The Longevity Labs, a company that sells spermidine supplements.

Madeo and Sigrist were already involved in a pilot clinical study in which 14 elderly people were given spermidine daily for three months. The results of this placebo-controlled study showed a slight improvement in memory in the group that took spermidine. The researchers’ new work supports these preliminary experimental results and addresses the physiological and cognitive effects of the compound.

For example, old mice given spermidine in their drinking water for six months were found to perform better than control mice on learning and memory tests (by associating a light stimulus with access to a reward and by getting to the location water), the team observed that the compound crossed the blood-brain barrier and steadily accumulated in the brain over a period of weeks. In the animals ‘hippocampi – a region of the brain associated with learning and memory – the team found that the compound promotes cellular respiration, significantly increases brain cells’ energy levels, and promotes modification of a protein called eIF5A, a translation factor that makes one Master autophagy regulator.

Similarly, compared to controls, flies fed spermidine showed improved memory and increased brain cell breathing, both of which were dependent on autophagy. And the treated insects showed the eIF5A modification, which Madeo and Sigrist’s team detailed in a second article on cell reports, also published this week. The modification, known as hypusination, involves the addition of hypusin, an unusual amino acid – so unusual that eIF5A is the only known protein it contains.

“It’s pretty convincing that they can show the same thing in mice and flies,” says immunologist Katja Simon from Oxford University, who was not involved in the study. On hypusinating eIF5A, which Simon’s team had previously reported promotes rejuvenation of immune cells in spermidine-fed mice, she added, “It was gratifying to see that they could see this in the brain [too]. Simon is a paid consultant for Oxford Healthspan, a company that sells a spermidine nutritional supplement but has no financial stake in the company.

In addition to the mouse and fly studies, the team also examined epidemiological data in humans. They examined cognitive test scores and nutritional reports from more than 800 older adults, and calculated participants’ spermidine intake using nutritional questionnaires. Five years after the start of the study (1990), the estimated spermidine intake correlated positively with the cognitive test results, with a higher intake also reducing the likelihood of cognitive impairment.

Overall, the work suggests that spermidine in food may aid improved cognition later in life, and points to the need for larger clinical trials to investigate the effects of spermidine on cognitive decline, according to Longo.

Although critical clinical evidence of spermidine’s cognitive benefits is lacking, Oxford Healthspan and The Longevity Labs are selling spermidine supplements for around $ 100 for a month. High amounts of this molecule can also be obtained cheaper by consuming wheat germ, ripe cheddar, soybeans, mushrooms, and other foods in which it is abundant.

S. Schroeder et al., “Dietary Spermidine Improves Cognitive Function”. Cell Rep, doi: 10.1016 / j.celrep.2021.108985, 2021.

YT. Liang et al., “Enhanced dietary hypusination of eIF5A protects against premature brain aging and mitochondrial dysfunction.” Cell Rep, doi: 10.1016 / j.celrep.2021.108941, 2021.