User:Akziq/sandbox

Evolution of aging edits:

DNA damage edits:
 * 1) Natural selection is a process that allows organisms to better adapt to the environment, it is the survival of the fittest which are predicted to produce more offsprings. Natural selection acts on life history traits in order to optimize reproductive success and lifetime fitness. Fitness in this context refers to how likely and organism is to survive and reproduce. It is based on the environment and is also relative to other individuals in the population. Examples of life history traits include; age and size at first reproduction, number of size and offsprings produced, and the period of reproductive lifespan. Organisms put energy into growth, reproduction, and maintenance by following a particular pattern which changes throughout their lifetime due to the trade-offs that exist between the different energy allocations. Investment in current vs future reproduction, for example, comes at the expense of the other. Natural selection, however is not so effective on organisms as they age. "Mutation accumulation (MA) and antagonistic pleiotropy (AP) are the key players that contribute to the deterioration of human survival with age, known as senescence. Both MA, and AP contribute to age-related declines in fitness." (Need to remove this and re-write)  The accumulation of random, germline age-related mutated alleles is known as mutation accumulation. Note that somatic mutations are not heritable, they are only a source of developmental variation. Studies done on Drosophila melanogaster have shown that mutation accumulation drives the combination of alleles which have "age-specific additive effects" that cause a decline in stress response and ultimately an age-related decline in fitness. The number of germ cell divisions per generation variable among lineages, and relative to genome size; for humans; 401 germ cell divisions occur per generation in males and 31 in females. (should I rewrite this?)
 * 2) A few studies in Drosophila have shown that the age of expression of novel deleterious mutations, defines the effects they contribute on mortality. Overall, however; although their frequency increases, their effects and variation decreases with age. There is no theory that explains how these deleterious mutations affect fitness on different ages and the evolution of senescence.
 * 3) Senescence is considered a by-product of physiology because our cell metabolism creates products that are toxic, we get mutations when we age, and we don't have enough stem cell that regenerate. Why did selection not find and favor mutations in ways that allow us, for example to regenerate our cells, or to not produce toxic metabolism? Why did menopause evolve? Because selection is more efficient on traits that appear early in life. Mutations that have effect early in life will increase fitness much more than mutations that manifest late. Most people have already reproduced before any disease manifest, this means that parents will pass their alleles to their offsprings before they show any fitness problems and it is therefore "too late" for selection. The two theories; "non-adaptive, and adaptive are used to explain the evolution of senescence which is the decline in reproduction with age. The non-adaptive theory assumes that the accumulation of deleterious mutations in the germline cause the evolutionary deterioration of humans with age." (Need to remove and re-write) These deleterious mutations start expressing themselves late in life, by the time we are weak/wobbly, and have already reproduced, this means that Natural selection cannot act on them because reproduction has ended. Studies done one Drosophila melanogaster have shown an inverse relationship between the mean optimal age at maturity and mutation rates per gene. Mutation accumulation affects the allocation of energy, and time that are directed towards growth and reproduction over the lifetime of an organism, especially the period of reproductive lifespan due to the fact that mutation accumulation accelerates senescence, this means that organisms must reach the optimum age of maturity at a younger age as their reproductive lifespan is shortened with accumulated mutation. The adaptive theory; first proposed by George C.Williams, by definition refers to antagonistic pleiotropy which is when the resultant relationship between two traits is negative. It's when one phenotypic trait positively affects current reproduction at the expense of accelerated senescence, growth, and maintenance later on. Antagonistic pleiotropy is permanent unless a mutation that modifies the effects of the primary locus occurs.
 * 4) Another theory of aging is known as the error catastrophe theory, proposed by Leslie Orgel in the 1960's. This theory states that cellular molecules which are required for basic cellular functions such as cell division and replication accumulate fatal errors which are detrimental and decline cellular survival. However, there has been a lack of evidence for this theory and it has therefore been disregarded by researchers.
 * 5) Mutations happen and they are completely random with respect to a need in the environment and fitness. Mutations can either be beneficial in which they increase an organisms fitness, neutral in which they do not affect and organisms fitness, or deleterious where they negatively affect an organisms fitness. Previously done experiments have show that most mutation accumulations are deleterious, and just a few are beneficial. Mutations of genes that interact with one another during the developmental process create biological and thus phenotypical diversities. Mutations are genetic information that are expressed among organisms via gene expression which is the translation of genetic information into a phenotypic character . Evolution is the change in heritable trait in a population across generations, since mutations generate variations in the heritable traits, they are considered the raw material for evolution. Therefore, beneficial mutation accumulations during the developmental processes could generate more phenotypic variations which increases their gene frequency, and affect the capacity of phenotypic evolution.

Telomere Theory of Aging Telomeres are recurring nucleotide sequences that protect the ends of our chromosome, they are sensitive to oxidative stress, and degrade during chromosomal replication. Telomerase is a ribonucleotide protein that helps repair and replace degraded telomeres. However, telomerase fails us as we age; it becomes less able to repair telomeres, and our whole body starts falling apart. This means that our cells can no longer divide, or divide with errors and that is the basis of aging. New research has also shown that there is an association between telomere shortening and mitochondrial dysfunction. Nevertheless, over expression of telomerase increases the chances of cancer. If telomeres stay in repair, there is a greater chance of longevity, but there is also more cell division and a greater chance of mutation which could result in cancer. Therefore, a long lived cell is just a time bomb. Enhancing telomerase activity is therefore not a solution, it only allows the cells to live longer. Fun fact: Naked mole rates have a high telomerase activity, they live long, and never get cancer, they are therefore an exception to this hypothesis.
 * 1) Just like DNA mutation and expression have phenotypic effects on organisms; DNA damage and mutation accumulation also has phenotypic consequences in older humans. Damage to macromolecules such as DNA, RNA, and proteins along with the deterioration of tissues and organs are the basis of aging. Species-specific rates of aging are due to deleterious changes which manifest after the reproductive phase ("It is generally believed that the cumulative effects of the deleterious changes that occur in aging, mostly after the reproductive phase, contribute to species-specific rates of aging" ) "Mitochondrial DNA (mtDNA) regulates cellular metabolism, apoptosis, and oxidative stress control" . Damage to mtDNA is therefore another contributing factor to phenotypes related to aging. Neurodegeneration, and cancer are two factors that manifest with DNA damage, therefore, we need to understand the change in association between DNA damage and DNA repair as we age in order to be aware of age-related diseases and develop lifestyles which could possibly promote a healthy life span.



There are different mutations that help extend the human life, most of these known mutations were found in C.elegans.