It is already known that the function of mitochondria declines with age, while aging is a known risk factor for several common age-related and neurodegenerative disorders. This led to the proposition that secondary mitochondrial dysfunction may lead to degenerative diseases.
New data published in the Journal of Anatomy indicated that spermidine-fed older mice exhibited higher numbers of mitochondria in their left ventricle than control older mice.
In addition, the mitochondria in the spermidine-fed animals were better organized within the heart muscle similar to what is observed in younger mice. However, they were elongated and thin, similar to what was observed in the older control mice, showing that spermidine consumption led to an intermediate stage between the young and old mice.
“It is tempting to speculate that the effect of spermidine on mitochondrial number is causally linked to its cardioprotective effects; however, this requires further analysis,” wrote scientists from Hannover Medical School (Germany), Medical University of Graz (Austria), BioTechMed Graz, and the University of Graz.
“Given the increasingly recognized importance of mitochondrial dynamics in cardiac diseases, it is likely that our observations do have a correlate in mitochondrial dynamics, thus relating them to mitochondrial function and/or quality control.”
Building the science
Spermidine is a polyamine compound that was originally identified in semen (hence the name) but is present in a variety of dietary sources, including wheat germ, soybeans, cheddar cheese, mushrooms, and mango.
As reported earlier this year by NutraIngredients-USA, the compound is receiving increasing attention for its significant promise in limiting the effects of aging. Several other studies gave reported the potential cognitive health benefits in humans, including a paper in 2018 in Cortex, which concluded that spermidine supplementation for three months was associated with “a positive impact on memory performance in older adults with subject cognitive decline”.
Aging is also associated with enlargement of the heart and progressive decline in function, with mitochondrial dysfunction a signature of the aged heart. Because spermidine stimulates both the removal (mitophagy) and creation of new mitochondria (biogenesis), the researchers examined the potential impacts of this compound in the hearts of aged mice.
The researchers divided old mice into two groups: Both groups consumed a standard lab mouse diet with one group receiving spermidine added to its drinking water. Another group of young mice were also included the study to act as another control group.
After six months of intervention, the researchers analyzed the hearts of the animals and found that all the older mice had a larger volume of the left ventricle and more heart muscle cells (cardiomyocytes), compared to the young animals. While the number of mitochondria was similar in both control groups, this number was significantly higher in the older mice fed with spermidine.
“This indicates that cardiac hypertrophy in the presence of spermidine was either associated with the generation of new mitochondria or with an increased mitochondrial fission or a combination of both,” wrote the researchers. “If mitochondrial fission is a requirement for mitochondrial quality control, then enhanced mitochondrial fission may attenuate age-induced mitochondrial dysfunction through fission-associated mitophagy.
“Mitochondrial density per unit of cardiomyocyte/myocardial volume was similar in the spermidine-treated aged and the young mice, indicating a balancing effect of spermidine on mitochondria.”
In addition, spermidine improved alignment of the mitochondria in the older heart, compared to the older control animals, but the shape and size variation of mitochondria was similar in both aged groups.
“In conclusion, mitochondria of the aged mouse left ventricle exhibited changes in number and 3D ultrastructure that is likely the structural correlate of dysfunctional mitochondrial dynamics. Spermidine treatment reduced, at least in part, these morphological changes, indicating a beneficial effect on cardiac mitochondrial alterations associated with aging.”
Source: Journal of Anatomy
Published online ahead of print, 27 December 2021, doi: 10.1111/joa.13618
“Spermidine supplementation influences mitochondrial number and morphology in the heart of aged mice”
Authors: J. Messerer, et al.