A number of proteins in the body play dual roles with respect to longevity – negative roles in some circumstances and good roles under other circumstances. I mention three substances in this regard: VEGF, telomerase and P16(Ink4a).
– VEGF stands for vascular endothelial growth factor, a family of growth factors , signaling proteins that play predominant roles in angiogenesis, the proliferation of new blood vessels. When the angiogenesis facilitates the viability and expansion of a cancer tumor, the result can be very bad for longevity. Also, VEGF defeats an important avenue the body uses to defend itself against cancer by causing dendritic cells to not work properly. Bad stuff! Under such circumstances the best thing to do is inhibit VEGF. On the other hand, when the body is repairing an injury, promotion of VEGF could be good, in fact required for healing to take place. VEGF is important for maintaining glomerular and other capillary integrity(ref), for example. A component of VEGF plays an important role in the survival of hematopoietic progenitor cells(ref), cells necessary for renewal of blood and other cells and longevity. Good stuff!
– Telomerase is a substance I have already discussed extensively, the substance that serves to enlongate the telomere caps at the end of chromosomes and therefore forestall replicative cell senescence. Some longevity researchers have thought that telomerase activation could be a golden key to enabling life extension since cell senescence may be at the heart of many kinds of diseases including cancers as well as age-related organ degeneration. Good stuff! But wait. Telomerase expression is turned on in most cancer cells, allowing them to replicate indefinitely and be immortal. So, most research on telomerase today is focused on finding substances that turn its expression off as a way of making cancer cells mortal again(ref)(ref). Bad stuff!
– P16(INK4a) is also a substance I have discussed in my Anti-Aging Firewalls treatise. On the one hand its increasing concentration with age provides a strengthening defense against cancers. It works by driving cells into senescence through cell cycle arrest as an alternative to them possibly becoming malignant. Good stuff! On the other hand, it “induces an age-dependent decline in islet regenerative potential” and reduces the ability of stem cells to proliferate. Bad stuff! As I have said before, P16/Ink4a works together with the three other genes to articulate a process of simultaneously protecting against cancers and shutting down adult stem cell function and regenerative capacity in aging tissues. Good stuff and bad stuff botIh!
These three Dr. Jekyll and Mr. Hyde proteins illustrate a key point with regard to longevity research: many pathways which promote healthy cell proliferation and organ renewal also promote cancer expression. Likewise, pathways important for inhibiting cancer proliferation also generally inhibit cell and organ renewal. The key issue is how to achieve the renewal affects without triggering or promoting cancers.
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