Antagonistic Pleiotropy and Free Radicals in Skin Tissue

Antagonistic pleiotropy is a term used to describe the results of a trait or mechanism that is beneficial in youth but then causes harm in later life. Evolutionary processes appear to select such traits due to their impact on early reproductive success, and that is one of the reasons why we age. Here, researchers illustrate this point while investigating one of the many roles played by free radicals in mammalian tissues:

When scientists bred mice that produced excess free radicals that damaged the mitochondria in their skin, they expected to see accelerated aging across the mouse lifespan - additional proof of the free radical theory of aging. Instead, they saw a surprising benefit in young animals: accelerated wound healing due to increased epidermal differentiation and re-epithelialization. Free radicals are especially reactive atoms or groups of atoms that have one or more unpaired electrons. They are produced in the body as a by-product of normal metabolism and can also be introduced from an outside source, such as tobacco smoke, or other toxins. Free radicals can damage cells, proteins and DNA by altering their chemical structure. Excessive amounts of free radicals are known to cause cellular damage that leads to aging, but in some mouse models and human studies lowering free radicals with antioxidants have not always conferred the expected benefits.

While increased free radical production showed benefit in younger animals, the mice paid a price over time. Mitochondrial damage from excess free radicals caused some of the skin cells to go into senescence - they stopped dividing and started accumulating. Over time the energy available to the epidermal stem cells was depleted - the stem cells simply became too scarce and the mice showed expected signs of aging, thin skin and poor wound healing. "In this case, we found unexpected pleotropic effects, mechanisms that benefit us when we're young cause problems as we age." Mitochondrial stress caused by the increase in free radicals also forced the skin cells in the younger animals to differentiate faster than normal, further depleting the pool of stem cells available to renew the skin over time. "This is not a simple process. It may be that nature used free radicals to optimize skin health, but because this process is not deleterious to the organism until later in life, past its reproductive age, there was no need to evolve ways to alter this mechanism." There could be one practical implication of the study: taking large amounts of anti-oxidants might have deleterious effects, at least in the skin.



Some speculation -
Perhaps eliminating free radicals would extend the animals' lifespans, by slowing stem cell differentiation/depletion in protected environments. Also, since neurogenesis resumes when mitochondria are protected [1,2], could the same mechanism be responsible for putting the brakes on neurogenesis (and, increasing neurosenescence) in adulthood? It seems that nature has optimized a number of pleiotropic processes to insure survival of genes, not longevity of the soma. Maybe also related is the theory proposed in [3].

[1] Discovery of a Pro-neurogenic, Neuroprotective Chemical

[2] Fertilizing Future Brain Cells
- Chemical helps newborn neurons reach maturity

[3] Is caspase-dependent apoptosis only cell differentiation taken to the extreme?

Posted by: Lou Pagnucco at August 4th, 2015 1:33 PM

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