Monday, January 17, 2011

Grow Taller with Anti-oxidants

This blog has spoken about Reactive Oxygen Species(free radicals) causing DNA damage before with Anti-Oxidants such as Astragalus, Acai Berry, Vitamin E, Phlomis Umbrosa, Melatonin, and Vitamin C all helping to fight off this damage.  As your activities increase more and more you produce more free radicals and thus you need more anti-oxidants.  One way to counteract this is via sleep which reduces the metabolic rate and gives the body the ability to mop up free radicals while not under so much pressure.  The more you increase your activity the more anti-oxidants or sleep you need.  Why are anti-oxidants so important for height increase?

Cell Contact Accelerates Replicative Senescence of Human Mesenchymal Stem Cells Independent of Telomere Shortening and p53 Activation: Roles of Ras and Oxidative Stress.

"Before transplantation, in vitro culture-expansion of MSCs is necessary to get desired cell number. We observed that cell contact accelerated replicative senescence during such process. To confirm the finding as well as to investigate the underlying mechanisms, we cultured both human bone marrow- and umbilical cord blood-derived MSCs under non-contact culture (subculture performed at 60-70% of confluence), or contact culture (cell passage performed at 100% of confluence). It was found that MSCs reached cellular senescence earlier in contact culture, and the doubling time was significantly prolonged. Marked increase of senescence-associated beta-galactosidase positive staining was also observed as a result of cell contact. Cell cycle analysis revealed increased frequency of cell cycle arrest after contact culture. It was noted, however, that the telomere length was not altered during contact-induced acceleration of senescence. Moreover, cell cycle checkpoint regulator P53 expression was not affected by cell contact. Marked increase in intracellular reactive oxygen species (ROS) and a concomitant decrease in the activities of anti-oxidative enzymes were also observed during contact-induced senescence. Importantly, increased p16INK4a following Ras up-regulation was found after contact culture. Taken together, cell contact induced accelerated senescence of MSCs, which is telomere shortening- and p53-independent. ROS accumulation due to defective ROS clearance function together with Ras and p16INK4a up-regulation play an important role in contact-induced senescence of MSCs. Over-confluence should therefore be avoided during in vitro culture-expansion of MSCs in order to maintain their qualities."

The inability to clear out reactive oxygen species resulted in cellular senescence.  If you look at HGH growth plates(the pictures are on page 4), you can see that growth plates without HGH are densely packed together whereas without HGH, the number of cells are about the same but they are further spread apart.  Therefore, increasing the amount of Extracellular Matrix within the growth plate may be a way to increase height be reducing cellular contact and therefore slowing down senescence.  Note that LSJL increases ECM.  Also, things like Hyaluronic Acid inhibits MMP-13 which degrades Extracellular Matrix.

So three methods of counteracting cell-contact based growth plate chondrocyte senescence:

1) Beta-Galactosidase inhibition
2)Decreasing cell contact by increasing ECM
3) Increasing the number of anti-oxidants to compensate for the cell contact inhibiting the ability for growth plate chondrocytes to fight off free radicals.

But Reactive Oxygen Species may also be important for growth...

Reactive oxygen species generated by NADPH oxidase 2 and 4 are required for chondrogenic differentiation.

"Although generation of reactive oxygen species (ROS) by NADPH oxidases (Nox) is thought to be important for signal transduction in nonphagocytic cells, little is known of the role ROS plays in chondrogenesis. We therefore examined the possible contribution of ROS generation to chondrogenesis using both ATDC5 cells and primary chondrocytes derived from mouse embryos. The intracellular level of ROS was increased during the differentiation process, which was then blocked by treatment with the ROS scavenger N-acetylcysteine(NAC is a dietary supplement). Expression of Nox1 and Nox2 was increased upon differentiation of ATDC5 cells and primary mouse chondrocytes, whereas that of Nox4, which was relatively high initially, was decreased gradually during chondrogenesis. In developing limb, Nox1 {LSJL upregulates Nox1} and Nox2 were highly expressed in prehypertrophic and hypertrophic chondrocytes. However, Nox4 was highly expressed in proliferating chondrocytes and prehypertrophic chondrocytes. Depletion of Nox2 or Nox4 expression by RNA interference blocked both ROS generation and differentiation of ATDC5 cells, whereas depletion of Nox1 had no such effect. We also found that ATDC5 cells depleted of Nox2 or Nox4 underwent apoptosis. Further, inhibition of Akt phosphorylation along with subsequent activation of ERK was observed in the cells. Finally, depletion of Nox2 or Nox4 inhibited the accumulation of proteoglycan in primary chondrocytes. Taken together, our data suggest that ROS generated by Nox2 or Nox4 are essential for survival and differentiation in the early stage of chondrogenesis."

If you look at the IGF-1 growth plates, you can see that the chondrocytes are more densely packed at all stages of differentiation. Maybe densely packing of chondrocytes stops the scavenging of Nox1, Nox2, and Nox4 and enables the chondrocytes to undergo further differentiation.

The solution is to find anti-oxidants that don't target Nox1, Nox2, and Nox4. So, don't take NAC if you want to grow taller. Apocynin inhibits the Nox's also.

Now the NADPH Oxidases are required for Chondrogenic Differentiation but as long as they are there we don't know if extra NOX's help increase height.  Probably not.  So as long as you aren't completely inhibiting the NOX's you should be fine in terms of growing taller.  Thus, focus on increasing the amount of Extracellular Matrix to decrease cell-to-cell contact to reduce growth plate senescence and grow taller.

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