So far the discussion has centered on theories of aging, with which I have no particular bone to pick. But this is not the crux of the debate. Glissandra claims that it’s mechanism of action is related to hormesis, a construct that says simply “what doesn’t kill you you makes you stronger”. However, i would be quick to add “what doesn’t kill you quickly may lead to chronic inflammatory disorders and slow death”. It’s all about the timing, dosing, signaling, molecular interactions, etc. In other words, the devil is in the details.Let me also say that I am a believer in hormesis and it’s therapeutic potential as a basic physiologic principle. The best known application may be exercise. It stresses physical systems, but they then recover and are stronger the next time challenged. Simple enough. But consider what would happen if you exercised all the time. I once had a patient who was obsessed with body fat and literally exercised herself to death. Exercise requires both a period of intense activity, and a period of recovery, to be beneficial. So, let me take a leap of logic and presume that this product causes a metabolic stress to the mitochondria of skin cells. But, it is not applied for an hour 3 times a week, it is applied twice daily, every day, assuming a constant rate of diffusion / absorption over that 12 hours from the cream. Toughens skin up (those cells that don’t die from the damage)? But wait – no recovery period. Won’t that just lead to chronic “cell danger response” signaling, and inflammation, with no down time to adapt? Maybe if the product sellers said to use it for a few days a month and then stop ….. at least that would match the paradigm.Also, this theory it does not comport well with what we know about the skin in responding to chronic oxidative stress. The most salient example? UV stress. We experience it daily, chronically, and the damage to skin accumulates over time. Yes, we have adaptive responses (e.g. repairing DNA damage every night, kill off and replace the worst damaged cells, create more melanin as a filter to sunlight). But even sunlight is only for half the day. But the adaptations don’t completely compensate for the stresses. Over time, the the system deteriorates. Skin ages. Too much of this stress and it also gets cancer. As the theory goes, what doesn’t kill you may toughen you. Perhaps the flip side is true – what doesn’t toughen you may end up killing you.I remain open to hormesis as a potentially beneficial mode of action for a dermal therapeutic, but would need to see specific evidence that ties a cyclical cellular stress to an adaptive (anti-inflammatory) response that is ultimately beneficial and does not lead to chronic inflammation and its consequences like disease, cancers, and aging itself.
Dr. John,
Thank you for your thoughtful question.
Glissandra (ie schisandrin B) differs from other conventional hormetic agents in that it has a wide range of effective doses which are non-toxic to normal cells. Schisandrin B is chemically transformed in various cells by cytochrome P-450 enzymes and thus produces signalling reactive oxygen species (ROS) which do not cause pathogenic oxidative stress. Instead, the ROS will elicit a glutathione antioxidant response, particularly in mitochondria, which results in mitohormesis - a process that can be induced by blocking insulin signaling, dietary restriction and physical exercise, which are all shown to be effective to prolong a healthy lifespan. Schisandrin B work in the same way in skin cells. The safeguard of mitochondrial function and antioxidant defense is beneficial to retard the skin aging caused by intrinsic (ROS) and extrinsic factors (solar radiation).
I look forward to our continuing to share more science behind our Glissandra products line.
Robert
structural integrity and functional ability over time. Consequently, cells experience impaired energy production, a decline in normal function, and accelerated free radical generation. This is the phenomenon of cellular aging, which makes the cell more prone to apoptosis, or programmed cell death – much like cell suicide.
ii Vitamins in Aging, Health, and Longevity, David R Thomas; The Division of Geriatric Medicine, Saint Louis University Health Sciences Center, Saint Louis, MO, USA.