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Senescence: Reversing the Clock on Skin Aging

By: Shyam Gupta, PhD, and Linda Walker
Posted: April 4, 2012, from the April 2012 issue of GCI Magazine.

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A large number of bacteria and tube worms survive extreme conditions of heat, cold and pressure—as evidenced in bacteria finds in hot water pools of Yellowstone National Park, ice shelves in Antarctica and thermal vents in deep ocean regions. Water is a key element for life. However, some organisms have evolved an amazing adaptation that allows them to survive under complete dehydration conditions for months or years until water is present again, at which time they resume their metabolism and growth. Anhydrobiosis (“life without water”) is found throughout all biological domains, for example in several species of eubacteria, archea, some fungi, certain invertebrate species, and “resurrection plants,” which survive near total desiccation, causing them to appear dead until rehydrated. Cellular anti-senescence agents act through compatible solutes to prevent cellular damage.

There are agents known to provide osmoprotection in non-mammalian organisms and plants. They include trehalose, maltose, sucrose, palatinose, cellobiose, gentiobiose, turanose, sorbitol, calcium chloride, amino acids such as proline and alpha-glutamate, peptones, taurine and taltrimide, among others. While use of humectants and emollients has been a common practice, the application of osmoprotective anti-senescence ingredients in human skin anti-aging has so far been practically unknown.

All the ingredients that speak to the biology of osmoprotection—sirtuins, DNA protection, mitochondria protection, glycation, telomerase, lifespan extension evoked by silent information regulator (SIR) proteins and so forth—interconnect with the ultimate goal: inhibit cell senescence. It is known that a close relationship exists among oxidative damage, senescence and aging. The examples of emerging evidence include: increasing nitric oxide (NO) bioavailability or endothelial NO synthase (eNOS) activity that activates telomerase and delays endothelial cell senescence; role of selenium in resisting senescence through its effects on cellular telomerase activity; activated oxygen free radicals cause peroxidative damage to all membranes and hasten senescence; carnosine, an endogenous free-radical scavenger, appears to be able to extend the life span of cultured cells, rejuvenate senescent cells, inhibit the toxic effects of amyloid peptide (A beta), malondialdehyde, and hypochlorite to cells, inhibit glycosylation of proteins and protein-DNA and protein-protein cross-linking, and maintain cellular homeostasis; potential anti-senescence gene Klotho (KL) has been found to participate in the progression of several different human cancers; cytokinin, 6-furfurylaminopurine (kinetin or Kin) influences on gene expression, cell cycle, stimulation of vascular development, delay of senescence and mobilization of nutrients; reactive oxygen species (ROS) induces senescence; and Bifidobacteria, which are a natural component of the bacterial flora of the human body and have a symbiotic bacteria-host relationship with human beings.

Aging, in fact, is associated with reduced numbers of beneficial colonic Bifidobacteria and impaired immunity, but the possible anti-senescence effects of Bifidobacteria are presently unknown. L-arginine may have an anti-senescence effect via the PI3K/Akt pathway; calcitonin gene-related peptide (CGRP) can counteract angiotensin II-induced senescence through downregulating the expression of NADPH oxidase and ROS production and increasing the production of Klotho; and Echinacoside, one of the phenylethanoids isolated from the stems of Cistanches salsa, a Chinese traditional herbal medicine, could protect cells from DNA damage and has potential anti-senescence activity.

Studies on the above clearly indicate controlling senescence may offer a singular ingredient that is the proverbial single bullet to manage skin aging.4–16

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