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Mutation accumulation

The first modern theory of mammal ageing was formulated by Peter Medawar in 1952. This theory formed in the previous decade with J. B. S. Haldane and his selection shadow concept. The development of human civilization has shifted the selective shadow as the conditions that humans now live in include improved quality of victuals, living conditions, and healthcare. This improved healthcare includes modern medicine such as antibiotics and new medical technology.Their idea was that ageing was a matter of neglect, as nature is a highly competitive place. Almost all animals die in the wild from predators, disease, or accidents, which lowers the average age of death. Therefore, there is not much reason why the body should remain fit for the long haul because selection pressure is low for traits that would maintain viability past the time when most animals would have died anyway. Evolution has not had an opportunity to select against deadly diseases such as cancer and heart disease. Metabolic diseases come along due to the low demand for physical activity in modern civilization compared to times where humans had to forage in the wild for survival.With the selective shadow now shifted, humans must deal with these new selective pressures.

Medawar's theory is referred to as Mutation Accumulation. This theory is based on the idea that random, germline mutations occur that are detrimental to overall health and survival later in life. Overall, senescence would occur through a summation of deleterious mutations, and would explain the overall phenotypic damage we associate with ageing.

Mortality

Mortality is the number of deaths in a particular group of people over a specific time period.There are two types of mortality: intrinsic and extrinsic mortality. Intrinsic mortality is thought to be a result of ageing from insider factors, whereas extrinsic is a direct result of environmental factors. An example would be that bats have fewer predators, and therefore have a low extrinsic mortality. Birds are warm-blooded and are similar in size to many small mammals, yet often live 5–10 times as long. They have less predation pressure than ground-dwelling mammals, and have a lower extrinsic mortality.

When examining the body-size vs. lifespan relationship, one also observes that predatory mammals tend to live longer than prey mammals in a controlled environment, such as a zoo or nature reserve. The explanation for the long lifespans of primates (such as humans, monkeys, and apes) relative to body size is that their intelligence, and they would have a lower intrinsic mortality.

Constant Failure Rate over Time

Diseases

Progeroid Syndromes

Progeroid syndromes are genetic diseases that are linked to premature aging. Progeroid syndromes are characterized by having features that resemble those of physiological aging such as hair loss and cardiovascular disease.

Progeria

Progeria is a single-gene genetic disease that cause acceleration of many or most symptoms of ageing during childhood. It affects about 1 in 4-8 million births.Those who have this disease are known for failure to thrive and have a series of symptoms that cause abnormalities in the joints, hair, skin, eyes, and face. Most who have the disease only live to about age 13. Although the term progeria applies strictly speaking to all diseases characterized by premature aging symptoms, and is often used as such, it is often applied specifically in reference to Hutchinson–Gilford progeria syndrome (HGPS). Children diagnosed with Hutchinson-Gilford progeria syndrome develop prominent facial features such as a small face, thin lips, small chin, and protruding ears. Although progeria can cause physical abnormalities on a child, it does not impact their motor skills or intellectual advancement. Those who have HGPS are prone to suffer from neurological and cardiovascular disorders.

Werner Syndrome

Werner syndrome, also known as "adult progeria", is another single-gene genetic disease. it is caused by a mutation in the wrn gene. It affects about 1 in 200,000 people in the United States. This syndrome starts to affect individuals during the teenage years, preventing teens from growing at puberty. There are four common traits of Werner's syndrome: cataracts in both eyes, changes in skin similar to scleroderma, short stature, and early graying and loss of hair. Once the individual reaches the twenties, there is generally a change in hair color, skin, and voice. The average life expectancy of someone with this disease is around 46 years. This condition can also affect the weight distribution between the arms, legs, and torso. Those who have Werner syndrome are at an increased risk for cataracts, type 2 diabetes, different types of cancers, and atherosclerosis.

Other Progeroid Syndromes

Bloom syndrome is a rare autosomal recessive disorder that is characterized by short stature, chromosomal instability, predisposition to cancer, and sun-sensitive skin. Those with Bloom syndrome can also have learning disabilities and have an increased risk of developing chronic obstructive pulmonary disease (COPD) and disease.

Cockayne syndrome is a homozygous or heterozygous mutation that results in short stature, abnormalities in head size, and slow growth and development.

Rothmund-Thomson syndrome is a rare autosomal recessive disorder that affects the skin. It is characterized by the sparse hair, juvenile cataracts, skeletal abnormalities, and stunted growth.