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A short essay about Aginf and Metabolism


-  Aging and metabolism -

Senescence, which is universally called aging, is the phenomena that refers to gradual decrease in functional characteristics of living organisms as time goes by. Senescence get attention in regards of the fact that all living organism undergoes the senescence and it can provoke aging-related diseases. In this essay, I will introduce theories of senescence including both direct and indirect cause of senescence, and recommendation based on them.

To exactly know what the senescence is, we must firstly identify why we have come to undergo aging process so that I brought 4 theories among the countless number of senescence theories.  Two of them are explaining the senescence in biological way: ‘Telomere theory’ and ‘DNA damage theory’, and other two are explaining in an evolutionary point of view: ‘selection shadow theory’ and ‘antagonistic pleiotropy theory’. 
Firstly, the selection shadow theory insist that the force of natural selection wouldn’t be applied to the phenotypes that appear in later stage of life so that senescence, which might have included bad characteristics for survival, didn’t have chance to be abandoned. The antagonistic pleiotropy, similarly, claims that the phenotype that is good for survival to be selected by force of natural selection is pleiotropic as functions badly for survival in later stage of life. In context of natural selection force, both of two theories see that the senescence couldn’t be chose by natural selection since senescence happens long after the sexual maturity. However, these two theories don’t suggest any direction to solve the senescence, only suggesting that the senescence is the result of natural selection force.
Telomere theory is about correlation between telomere and senescence, based on the fact that somatic cells of which telomerase expression is low show senescence and have short telomere. Actually, Turritopsis nutricula, a kind of jelly fish expresses telomerase in abundant level so that is theoretically immortal. But long telomere is not always good for organism since it also increases the rate of cancer and the obvious pathway of how telomere is engaged in senescence is not clearly identified yet.
Lastly, DNA damage theory is that the accumulated damages on DNA by both endogenous(ROS, Replication error, malfunction of DNA repair system, etc) and exogenous source(UV, smoking, chemicals, etc) result in the senescence. In a broad way, it seems that DNA damage theory includes the telomere theory as well in terms of relationship between genomic instability and senescence. Anyhow DNA damage theory can explain the causes of genomic instability in various way including both endogenously and exogenously so that it clearly gives us direction to solve the senescence: How can we conserve our genomic integrity?

In terms of preventing DNA damage, there are two way: block the exogenous factor and reduce the endogenous factor. 
Actually it is easy to control the exogenous factor that can affects to the DNA damage (ex. UV light, chemicals, smoking, etc) since it doesn’t matter as long as we keep them away from ourselves.
For endogenous factor, it is necessary to understand the pathway in which they are generated and we should think about how we will control their level. The representative endogenous source of senescence, the reactive oxidant species(ROS), is formed during normal metabolism and it can provoke DNA damage. If the DNA damage occurred in gene that engaged in DNA repair system, the mutation rate will more increased which can lead to the decline of biological function or even cancer. Targeting to this oxidative stress, our body system has scavenging pathway which reduce the oxidative stress. For example, NAD, which is Nicotinamide Adenine Dinucleotide, is strong antioxidant that engaged in scavenging pathway. In a same context, by identifying the senescence causing factors in endogenous pathway, the antioxidant agents (such as Melatonin, SIRT1) can be proposed as key of aging problem.

Even though aging is not fully understood yet, the new discoveries suggest the way to solve it one by one and it allows us to realize what to do based on above theories: take something good for scavenging such as NAD, melatonin and avoid exogenous factors like UV lights and smoking. 
In my opinion, the controversial about ‘aging’ is quite similar to the controversial about ‘evolution’ in past days because aging seems like it is more of mixture of many theories than only one specific theory, like the evolution is. Therefore I think it is better for people to understand the senescence in a broad sense and I hope this paper was helpful in that regard.