Resveratrol and PQQ
In a recent post a reader asked if a claim can be made that resveratrol and PQQ are direct opposites of each other. He cited the literature that points to pyrroloquinoline quinone’s role in early growth and the claims made that Resveratrol activates sirtuins in the absence of growth factors. The idea being that the longevity gene FOXO3 localizes in the nucleus and activates key longevity genes. He posited that research indicates pyrroloquinoline quinone might cluster around bone marrow, therefor making the leap that the mitochondria are probably bigger, whereas resveratrol mitochondria are smaller and more pervasive in muscle fiber. Although these propositions are interesting. As a constructive criticism, the propositions do go beyond what is currently know about both compounds. For example, the data regarding cell signaling and PQQ is far from complete (e.g., it rests on less than a dozen of somewhat focused, albeit rather promising studies, done over the past ~6 years). Although mechanistic studies on resveratrol at the cellular level now extend well over a decade, there are still many details to resolve. As an example, the role of sirtuins in multiple metabolic and age-related pathways has been established and a link to resveratrol has been made, but whether resveratrol is a direct activator of such pathways (in contrast to an indirect modulator) remains unclear and the mechanisms remain poorly defined. In this regard, studies focusing on the sirtuins and PQQ have not been done, so it is difficult to make that direct comparison. Where comparisons can be made involve factors, such as PGC1-alpha (peroxisome proliferator-activated receptor gamma co activator 1-alpha) or TFAM (transcription factor A, mitochondrial), several of the many factors important to mitochondriogenesis and the programmed turnover of mitochondria, often referred to as apoptosis. The control of mitochondrial amount, shape, and size in cells is the result of a careful balance between both synthesis and degradation (apoptosis). This point is important to appreciate. In addition to the many compounds that may be involved, which act as co-activators and activators, there is the coordination of dozens of cell signaling pathways that help to maintain the balance. Regarding mitochondrial size, what data that are available suggest that there is no change in mitochondrial size in response to changes in PQQ dietary status (Pyrroloquinoline Quinone Modulates Mitochondrial Quantity and Function in Mice), although mitochondrial amount and number are affected. In the PQQ papers, “growth factor” is use generically to mean a naturally occurring substance capable of the stimulating, proliferation and/or differentiation of cells. It does not infer or routinely imply a change in a given cellular organelle’s size, such as mitochondria. Moreover, the reports to date do not support that the effects of resveratrol or PQQ are particular organ specific. Rather, markedly different cell types respond to PQQ and resveratrol exposure, often at the descriptive level, with a similar effect (e.g. an increase in mitochondrial amount or protection from ischemia).