A YouTube search into premature aging will give you a couple of videos featuring young adults whose life is only limited by their bodies and not their ambitions. Harboring a condition collectively termed as Progeria, they are given only an average of 15 years to live; not necessarily because of a terminal illness like cancer in most cases but because their bodies age 10 years for every 1 year of their lives. As saddening as this is, young adults are beaming with energy and live life to the fullest. As such most defy the odds and pass the 15 year mark.

A Look into Progeria

Progeria are a group of syndromes characterized by premature aging. The most severe case of Progeria which we will talk about is known as Hutchinson Gilford Progeria Syndrome (HGPS). Kids born with HGPS appear normal at birth. However after one year they experience retarded growth and soon after the hair starts falling off. As the years progress they do not gain any weight and have no subcutaneous fat.

While into their teenage years, they experience health problems common to the elderly. HGPS patients eventually die of stroke, myocardial infarction or cardiovascular heart disease.

What Goes Wrong: Premature Aging

HGPS syndrome is an inherited genetic disorder where the child is born with a mutation in a gene called LMNA. The protein known as Lamin A encoded by this gene does not develop into its functional form. As such kids with HGPS have a premature form of Lamin A known as progerin.

Lamin A is one of the proteins used in the crucial function of repairing DNA damage, specifically Double Strand Breaks (DSBs). DSBs can be repaired in two ways: through homologous Recombination (HR) or via Non Homologous End Joining (NHEJ). Each mechanism is important to the body in its own unique way.

Damaged DNA that require repair through HR then use Lamin A to stabilize the final proteins used in the repair. Without a functional Lamin A patients with HGPS cannot repair this damage. The damage then accumulates and results in the accelerated aging commonly observed in HGPS.

What the happens is that during birth, the cells in HGPS patients having no significant damage do not show any signs of a problem. The child looks normal. With time, exposure to endogenous and exogenous DNA damaging factors cause DNA damage that goes unrepaired. The specific damage, double strand breaks are one of the most lethal forms of DNA damage.

Genome Instability

Unrepaired DNA damage or genome instability predisposes cells to either one of two things: cancer or a loss of function. Every mutation is usually unique in the way it is expressed. This is because genes do not work individually but work as a pattern. The specific part of the pattern disrupted as a result of mutation determines whether the mutation progresses to cancer or a loss of function. In the case of HGPS, patients do not have cancer but instead have the latter: a rapid loss of tissue function at the cellular level.

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In “normal” aging, various studies have proved that some DNA damage repair pathways become compromised. With HGPS the compromise in Homologous Recombination is certain since it is inherited. However in “normal” aging, the enormous damage our genome encounters every day inevitably compromise one of our repair pathways.

Normal aging then boils back to the fact that we encounter DNA damage whose nature predisposes it to be repaired using the same gene (s). This damage certainly goes unrepaired and translates into a mutation similar to HGPS. Evidently the genome in all aged cells have one mutation or another with some cells even showing the presence of progerin.

The use of ethical gene correction in reversing aging then goes beyond extending life past the normal 70 year mark and rather expands to saving these beautiful souls subjected to premature aging while not forgetting people with other inherited genetic disorders.

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