According to Northwestern Medicines scientists, the first genetic mutation that protects against various factors of biological ageing in humans has been discovered. The genes were found in an extended family of Old Older Amish, living near Berne, Indiana.
The Amish kindred in Berne, Indiana, are genetically and culturally isolated and most of them are at least distantly related. The ancestors of the Indiana Amish emigrated in the middle of the 19th century from Berne, Switzerland.
People with the mutation live to 85 years on average.
The Amish with the mutation are also less prone to diabetes and lower fasting insulin levels. Even the vascular age is lower, which means retained flexibility in blood vessels that are carriers of the mutation.
The molecular marker of aging (telomere length), the metabolic marker of aging (fasting insulin levels) and the cardiovascular marker of aging (blood pressure and blood vessel stiffness); all track in the same direction for these individuals which indicate protection of age-related changes.
Amish kindred with mutation went on to live 10% longer and have 10% longer telomeres, as compared to Amish kindred without the mutation.
A “longevity” drug that is up for experimentation is believed to recreate the effect of the mutation and is now being tested in human trials. The trails are conducted to see if it provides protection against some aging-related illnesses.
The Amish individuals hold very low levels of PAI-1 (a protein that comprises part of a “molecular fingerprint” related to aging or senescence of cells).
In the wake of mutation’s effect on insulin levels in the Amish, trials will be initiated by Northwestern to examine the effects of the new drug on insulin sensitivity on individuals with type 2 diabetes and obesity.
Northwestern’s new study had scientists examining individuals who had one mutant copy of the gene, rendering their level of PAI-1 about half the level of kindred with two normal copies.
The ones who were carriers of gene mutation had about 30% lower fasting insulin levels and protected from diabetes.
An experimentation of PAI-1 on mice has even shown that it can protect Alzheimer’s like pathology.
Since the Amish kindred are missing a healthy level of PAI-1, they have increased chances of a breakdown of clots and abnormal bleeding that is associated with heavy menstrual bleeding, bleeding with pregnancy and ovulation, dental work, injury, and trauma.
With so many benefits of a PAI-1 mutation being discovered, scientists also took to investigating the effect on the cardiovascular functions. It was found that individuals with two changed PAI-1 genes not only had a bleeding disorder but also had varying degrees of an unusual cardiac disorder that leads to fibrosis (scarring of the heart).
PAI-1 specifically inhibits the clot-dissolving protein called t-PA, which was developed to treat people having heart attacks and strokes.
In the U.S., Northwestern is partnering with a Japanese startup company (Renascience) which will develop a new class of drugs that will specifically target PAI-1.
Based on the drug’s effect on hair growth in mice, Renascience has licensed a formulation to an American company, Eirion Therapeutics, Inc., that will take forward the development of a topical formula that will be tested for the treatment of male pattern baldness.
Scientists also speculate that PAI-1 inhibitor drug boosts the number of red and white blood cells and platelets of patients who have undergone chemotherapy.
The research was supported by National Heart, Lung and Blood Institute of the National Institutes of Health.
Phew! Seems like a wonder drug is on its way, thanks to the Amish!
Information source: northwestern
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