Studies Of Caloric Restriction, Resveratrol And Sirt1 Demonstrate A ?Metabotype’ Continuum From Cellular Rejuvenation To Aging To Cancer
|
ratio, just as is the time from birth to the elevated cancer risk incidence curve. Instead, they seem more tied to the mitochondrial decay rate as per life expectancy. It is as if the vast array of environmental constraints set the necessary life length of the organism and that cellular metabolism doesn’t have a very difficult time complying by setting juvenile and adult stage length as needed. Of mice and men; old at age three or old at age 100; several thousand percent difference in life expectancy and 99% identical metabolic pathways. This gives argument to the notion of not what, or how you do something, but when you do it. It probably works the same in mice as it does in men, with the switches being turned off and on at different times and at different strengths. The central metabolic system, and its core regulatory elements haven’t changed much since the most advanced animal was a sponge. In retrospect, glycolysis and aerobic respiration are systems entrenched in times so ancient, that it was before earth even had an oxygen atmosphere. When early oxygen producing photosynthesis first evolved in the ocean, anaerobic glycolytic bacteria, in one or more branches of life, began oxidatively extracting energy from glycolytic end products by removing hydrogen and adding oxygen in a stepwise process. Eventually this oxidative process evolved to extract the maximum obtainable energy by extending the oxidative chain all the way to the natural carbon dioxide and water, as waste product, endpoint. A symbiosis was formed when a nucleus containing archaeobacterial species housed an aerobic bacterial life form within itself, probably providing predatory protection in exchange for abundant energy. This is a relationship similar to that which exists today when coral polyps house algae within themselves. Before the first sponge-like simple multicellular life forms evolved, a nearly billion year relationship between the host and its symbiont had been maturing. Eventually, this relationship became so inextricable that, by the time that the first eukaryotic fungal/animal precursor cell arrived, the aerobic symbiont had been mostly reduced to the status of slave to its host, giving up most of its genome in exchange for providing critical energy producing advantages to its host (except for the notable, and rather disturbing distinction of retaining a host cell killing command center, called apoptosis). We call this relic, the mitochondrion. Today, the animal cell mitochondrion contains only the genes for its respiratory chain and some of its protein synthesis and replication machinery, cell suicide mechanism, included. All other ancient pre-mitochondrial functions are now sequestered in the DNA of the cell nucleus, and their gene products are imported into the mitochondrion from the cytoplasm. This is true in even though most primitive animal life forms, and in even earlier life forms, such as single celled yeast. Thus, aerobic and anaerobic systems were intricately enmeshed, in terms of each others operation and control mechanisms for a period of time longer than the existence of the Kingdom Animalia. It is no small wonder that we see the birthings of a SIRT1 control system in organisms that predate the animal kingdom. It seems incredible how both deeply entrenched and unchanged the caloric restriction response system has remained over time. We find it throughout the entire animal kingdom, from worms, through insecta, up the vertebrate tree, from ancient to modern life forms. The system is also remarkable in its versatility, and in its short term, intermediate term and its long term applications to organismic, species and Kingdom survival. When we look at mammals, in our attempts to utilize models more akin to our human selves, we see the sweeping SIRT1 system applies to every tissue and organ tested. Although the SIRT1 cascade ‘rejuvenation’ is nowhere near to being confused with the word ‘immortalization’, it is an apt nomer, nonetheless. Among other things, the system institutes production, via mitochondrial biogenesis, of efficient catabolism, which yields survival advantages during
Related posts:
|
