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Accumulation of Progerin

Accumulation of Progerin

This theory of aging is related to the noticeable symptoms of “Hutchinson-Gilford Progeria Syndrome (HGPS)”. HGPS is an astronomically unusual yet well-researched genetic disease. Children that are born with HGPS get old at an unusual rate. Signs of old age are manifested at a very early time-interval where wrinkles, baldness and adversity of cardiovascular disease cause death at the age of 14.

It is only recently that this old age phenomenon has been deciphered. Masters in research fields spotted both the cause and the eventual cure for HGPS as well as making it a new theory of aging. There is still a long-way to go. Here an overview of the theory is provided.

HGPS

Hutchinson-Gilford Progeria Syndrome is a result of “LMNA gene” mutation. LMNA gene produces lamin protein that is the structure that actually envelopes the nucleus in cells. The result of the mutation is that lamin is “farnesylated” and incapable to “evolve into a mature Lamin A”. Progerin is the name for the farnesylated lamin.

Progerin

The progerin tends to concentrate to the nuclear envelop of cells. “This interferences with consistency of the nuclear envelope can result in misshapen cell nuclei”. This mechanism is strongly believed to be a “fundamental symptom of HGPS”.

Experimental Science

It was proposed to experiment the effect of inhibiting farnesylation of progerin. The research appeared to give interesting facts. When misshapen cells were treated through progerin inhibiting farnesylation with “FTI (farnesyltransferase inhibitor)”, normal cell shapes could be restored (Possible references, Study 1, study 2, study 3, study4). FTI does eventually prevent the farnesyl chemical group from progerin. FTIs are anti-cancer drugs that have recently been developed.

Furthermore, FTI drug Tipifarnib (Zarnestra) was used in a mouse model. It appeared to act as protectionism against “cardiovascular disease”. This heightens the belief that HGPS can be treated with FTI.

Clinical Trials

Since May 2007, FTI therapy for patients suffering from HGPS has been ongoing. For the research it was extremely hard to find patients as the disease is extremely rare. Now, 28 children from 16 countries are involved in the research. Findings are expected to be published in 2010. For more information, check “The Proegeria Research”.

Relation to Normal aging

From research on HGPS to healthy individuals, progerin seems to have certain related factors. Progerin might be a ruling mechanism for physiological ageing. It has been shown that cell nuclei in relatively old people have similarities to those of HGPS patient cells. This does both include histone modifications as well as augmented DNA damage. Eventually, nuclear defect is produced by sporadic use for healthy individuals and this cryptic splice appears to be the same as the lamin A causing HGPS. It could be possible that altering the “nuclear defect related to aging can actually counteract on the aging process”.

In line with this research, it has been found that progerin is generated through aging. A Swedish research team has evaluated the inducement of progeria gene and found that as people age more and more “progerin RNA is produced”.

Research is constantly evolving in the same direction. It has been found that progerin has other shortcomings on our bio-molecular signaling such as evoking problems in stem cell differentiation. Progerin causes interaction with cell division in “normal and HGPS cells”. “Another study showed” that progerin affected the cell culture in the differentiation of adult mesenchymal stem cell. It tended to increase the rate of maturity of tissues. This is supported with facts from HGPS patients approving both physiological and tissue aging.

Growing Theory on Aging

This is a growing aging theory. It has been concluded that accumulation of progerin in typical cells causes similar effects to HGPS patients. However, the use of FTIs isn’t qualified as a certain methodology to treat progerin accumulation in normal cells. Hence as a theory on aging, research on progerin must still evolve further so that solid medical and therapeutical treatments can be made available.

Further Reading
Road Map to anti-aging Theories

Main Reference
1. Anti- aging firewalls the science and technology of longevity.

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