In Aging Cell, researchers have published detailed information on why the antioxidant pyrroloquinoline quinone (PQQ), which is known to be safe in humans, alleviates age-related disc degeneration in mice.
A return to antioxidants
Oxidative stress was once considered to be the core of aging, a concept that has since been supplanted by more detailed and accurate theories. However, oxidative stress still plays a role in aging and age-related diseases. Intervertebral disc degeneration (IVDD), for example, has oxidative stress [1] and cellular senescence [2] among its causes.
PQQ, a compound that the FDA recognizes as safe in humans, is a water-soluble, vitamin-like compound that naturally occurs in foods and has a strong affinity for the free radicals that lead to oxidative stress [3]. As these researchers have previously investigated its potential use in fighting osteoporosis [4], they moved on to determine whether or not it might be capable of mitigating IVDD.
Antioxidant and anti-senescent
This study was conducted in a population of 24-month-old male mice that were fed a diet containing extra PQQ for the latter half of their lives, comparing them to 12-month-old males and 24-month-old males that had received a normal diet. While this supplement did not entirely alleviate IVDD markers to the levels of the 12-month-old group, it had significant impacts in these animals: the treated mice had larger discs along with chemical biomarkers and cell numbers that were more like those of younger mice.
Biomarkers related to senescent cells and the degradation of the extracellular matrix (ECM) were also positively affected. Both senescent cell populations and the inflammatory chemicals they secrete were reduced, as were signs of overall oxidative damage. There were also signs that the treated mice had fewer cells dying of apoptosis than their age-matched counterparts.
A pathway explored
Looking deeper, the researchers found the biochemical pathways responsible for this difference. A molecular binding model found that PQQ interacts with the Keap-Nrf2 complex in a way that activates Nrf2, which cells naturally produce as an antioxidant [5]. Further analysis revealed that this was the cause of its anti-senescence effects.
This increase in Nrf2 was also found to upregulate Wnt5, a compound that was previously found to have positive effects against IVDD [6]. PQQ did not have this positive effect on cells that can’t express Nrf2, thus demonstrating that this is the actual pathway involved. Further experiments on mice that did not produce Nrf2 demonstrated that these animals suffered from IVDD and other age-related disorders early in life; as expected, PQQ had no effect on these animals.
These results were only conducted on a population of male mice who took it for half of their entire lives. Further experiments by other research teams on other animals are necessary to verify whether or not this sort of long-term exposure to PQQ might be beneficial against IVDD or other age-related diseases in human beings.
Literature
[1] López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2023). Hallmarks of aging: An expanding universe. Cell, 186(2), 243-278.
[2] Novais, E. J., Tran, V. A., Johnston, S. N., Darris, K. R., Roupas, A. J., Sessions, G. A., … & Risbud, M. V. (2021). Long-term treatment with senolytic drugs Dasatinib and Quercetin ameliorates age-dependent intervertebral disc degeneration in mice. Nature Communications, 12(1), 5213.
[3] Akagawa, M., Nakano, M., & Ikemoto, K. (2016). Recent progress in studies on the health benefits of pyrroloquinoline quinone. Bioscience, biotechnology, and biochemistry, 80(1), 13-22.
[4] Li, J., Zhang, J., Xue, Q., Liu, B., Qin, R., Li, Y., … & Yang, R. (2023). Pyrroloquinoline quinone alleviates natural aging‐related osteoporosis via a novel MCM3‐Keap1‐Nrf2 axis‐mediated stress response and Fbn1 upregulation. Aging Cell, 22(9), e13912.
[5] Niture, S. K., Khatri, R., & Jaiswal, A. K. (2014). Regulation of Nrf2—an update. Free Radical Biology and Medicine, 66, 36-44.
[6] Li, Z., Zhang, K., Li, X., Pan, H., Li, S., Chen, F., … & Liu, H. (2018). Wnt5a suppresses inflammation-driven intervertebral disc degeneration via a TNF-α/NF-κB–Wnt5a negative-feedback loop. Osteoarthritis and cartilage, 26(7), 966-977.
View the article at lifespan.io
