Spermidine-Rich Foods to Reverse Aging of the Immune System and Heart

Maintaining a robust immune system is critical to successful aging. During a typical flu season, for example, about 90 percent of the deaths occur in people older than 65 years. Vaccines help too, but their efficacy too relies on having a well-functioning immune system.

To sustain enduring protection, we have “memory” immune cells that can live for decades on high alert, providing a long-lasting defense against pathogens we may have only encountered in childhood. Immunity to diseases like chickenpox and measles can last a lifetime thanks to these methuselian antibody-producers.

The longer cells live, though, the more prone they are to accumulate intracellular waste. That’s where autophagy comes in. Yet, as we age, levels of the autophagy-inducer spermidine in our immune cells drop, a decline in autophagy follows, and their ability to function declines. So, if we restored spermidine to youthful levels, might we me able to rejuvenate antibody production? Researchers decided to put it to the test.

White blood cells were obtained from donors aged 65 and older. Replenish spermidine levels and not only was autophagy restored, but antibody production improved, suggesting that spermidine may help “reverse immune aging.” It did not seem to be just a general immune boosting effect (for example, spermidine doesn’t affect antibody production in cells from young donors), but rather an immune rescuing effect through the restoration of earlier spermidine levels. The next step will be to see whether this spermidine-induced revival in immune function translates into disease resistance or survival in a clinical trial.

As we age, our hearts start to fail as well. However, add some spermidine to the drinking water of aged mice—even starting late in life—and structural and functional heart defects can be reversed. In the accompanying editorial “Spermidine to the Rescue for an Aging Heart,” a senior investigator at the National Institute on Aging suggested that since spermidine has no known side effects and is present in many foods, “it could be relatively easy for most people to get the benefits of spermidine through dietary modifications…”.

Spermidine can also shrink the inflammatory cores of atherosclerotic plaque in the arteries of mice fed a diet chock full of sugar and butterfat. These effects were found to be driven by autophagy, perhaps due to the purging of dysfunctional mitochondria from the heart muscle cells and the clearance of cholesterol from the arteries, but spermidine may also help independent of autophagy.

The ability of the endothelial lining of our arteries to generate the “open sesame” molecule nitric oxide declines with age. This interferes with the capacity of our arteries to dilate. Interestingly, nitric oxide is made from arginine, the same amino acid that’s used to make spermidine. So, when we eat spermidine-rich foods, our body has to make less from scratch, freeing up more arginine for nitric oxide production. Perhaps this is why dietary spermidine lowers high blood pressure in rats and reverses arterial aging in mice. To elucidate the mechanism, Boston University researchers scraped endothelial cells from the blood vessels of volunteers.

Adding spermidine to the retrieved endothelial cells restored nitric oxide activity and reversed endothelial cell dysfunction, but these benefits were blocked by autophagy inhibitors. Therefore, autophagy may be critical for healthy human artery function. Yet, comparing the arteries of those in their 60s to those in their 20s, endothelial autophagy indicators appear to deteriorate by about 50 percent. So, do people who eat more spermidine have less cardiovascular disease? Yes. Higher levels of dietary spermidine were found to correlate with reduced blood pressure and a lower combined incidence of heart attack, stroke, and death from vascular disease.