Questions from Dr. John and the answers from Prof. Robert in the BFT debate

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  drjohn

  JULY 29, 2014 AT 5:01 PM · REPLY

  Welcome to the debate, it is a pleasure to have you here.

  Now to start I need to explain to our readers that this discussion involves evolving theory in the realm of cell biology that even the average PhD would have difficulty understanding unless they are actively involved in researching these topics. Once we set the stage I will endeavor to focus in on what we call the translational research. Basic facts & hypotheses are translated to prototypes and products, and are tested for clinical utility in a way that affirms or dismisses the underlying theories. At the end of the day we realize that what interests most folks is insight into things that work, and why they work. Theory without tangible application interests scientists, not consumers.

  The hyptotheses we are talking about here have to do with mitochondria, the energy factories present within cells of all types. It turns out the mitochondria are very important determinants of cell fate (cell death or survival from stress or injury), and thus are a center of focus for theories of aging. Now, it may be important to point out that whole organism aging and skin aging (or the appearance of same) at times may diverge, and thus manipulations of one don’t necessarily correlate with changes in the other. In simple human terms,living to 110 does not mean your skin will look young at 50. In some ways, the opposite may be true. So, we need to carefully dissect theories and experiments that have to do with theories of aging, mitochondrial energetics and ROS, tissue survival, etc, to make sure at the end of the day that the chain matches up.

  As clinicians we often think backwards. Start with the problem and potential solution, then track backwards to find physiologic explanations that make sense. Let’s start with some basic questions for Dr. Ko from which we can work backwards.

  1. What is the clinical evidence that Glissandra effects anti-aging benefits on skin? How are they documented?
  2. How is the active delivered? What vehicle? In what doses? Continuous vs discontinuous? How deeply does it penetrate?
  3. How is Glissandrin transported into cells to affect mitochondrial functions? By which known mechanism?
  4. What cell populations in skin is it affecting?
  5. If there is ROS signaling – what is the signal cascade? What other well known biochemicals are affected?
  6. As with other mitochondrial stressors is there a shift toward anaerobic glycolysis?

  Thanks in advance.

Professor Robert Ko

August 2, 2014

Dr. John, please find below my answers to your questions.

Respectfully, Robert

1. What is the clinical evidence that Glissandra effects anti-aging benefits on skin? How are they documented?

已經證明，以防止在體內和在體外通過太陽能光照射引起的氧化損害。

lol - okay even us scientists need to have a sense of humour!

Seriously though, Glissandra has been shown to protect against oxidative damage induced by solar light irradiation both in vivo and in vitro.

Two clinical trials using Visual anti-aging assessments were conducted. The duration of the studies were 8 weeks. Data collected were tabulated and analyzed.

North American Trial

Visual anti-aging assessments from 35 subjects of diverse ethnicities, with ages ranging from mid 20’s to late 60’s, from both genders.

South East Asia Trial

Visual anti-aging assessments from 28 subjects of Asian ethnicity with 17 subjects with age <45, 8 subjects with age 45-55, 3 subjects with age 55-65, from both genders.

Both studies documented dramatic effects on various signs of skin aging from end users.

2. How is the active delivered? What vehicle? In what doses? Continuous vs discontinuous? How deeply does it penetrate?

The active is delivered by passive diffusion. The active is lipophilic, and is readily absorbed by skin.

3. How is Glissandrin transported into cells to affect mitochondrial functions? By which known mechanism?

Glissandrin is readily transported via diffusion into the cytoplasm and then mitochondria . The active compound is metabolized by cytochrome P-450 enzymes (in both cytosolic and mitochondrial compartments), with resultant generation of signaling ROS which in turn activate the MAPK/Nrf2 pathway. The consequent increased expression of antioxidant genes can enhance the mitochondrial antioxidant capacity and thus the mitochondrial ATP generation.

4. What cell populations in skin is it affecting?

As the active compound of Glissandra is bioavailable to all tissues in the body, it is reasonable to assume that Glissandrin is bioavailable to all types of skin cells.

5. If there is ROS signaling – what is the signal cascade? What other well known biochemicals are affected?

The signaling cascade involves the redox-sensitive MAPK/Nrf2 pathway. The activation of Nrf2 increases the expression of antioxidant genes such as enzymes in the glutathione antioxidant systems and superoxide dismutase, etc.

6. As with other mitochondrial stressors is there a shift toward anaerobic glycolysis?

Glissandra differs from other metabolic stressors in that it won't increase the cellular energy demand and thus a shift toward anaerobic glycolysis.