A dwarfism-causing mutation slowed aging and protected against heart disease
Some rare mutations disrupt human development, causing a person to have a very short stature. Sometimes these genome alterations also cause serious diseases. However, according to a new article, the authors of which examined 24 people with one of the hereditary forms of dwarfism, those, on the contrary, boast a healthier heart and in general slower aging.
Aging is a complex process that occurs through multiple mechanisms. Some scientists believe that aging is a real disease that can and should be treated. In this case, it is useful to know what genes are "to blame" in it and what mutations and biochemical processes will help slow down the destruction of the body.
New data on this subject received from an unusual source - during the examination of patients with one of the forms of hereditary dwarfism. People with the so-called Laron syndrome have normal levels of growth hormone (somatotropin), which is necessary for body and organ enlargement, but too little insulin-like growth factor-1 (IGF-1). Normally, the two molecules work in conjunction, and a deficiency of one of them disrupts the growth of bone and other tissues.
The disease is inherited from parents and leads to a severe reduction in growth - adults with Laron syndrome do not grow taller than 120-130 centimeters. However, the disruption of hormone-mediated signal transduction has other, unexpectedly beneficial effects. People with such mutations are less likely to get cancer, also because their DNA is less damaged. If this happens, the affected cells usually commit "altruistic suicide" and save the body from the disease.
Moreover, Laron syndrome "protects" against diabetes, insulin resistance, and cognitive impairment later in life. The only thing missing from this list of so-called age-associated diseases - satellites of aging - was cardiovascular pathology. The gap was filled by a new article in the journal Med. It shows that people with dwarfism do have healthier hearts and generally age more slowly.
The authors studied the health of 24 subjects with Laron syndrome from Ecuador. They represent the South American population, which accounts for a third of all patients with this diagnosis in the world - scientists have been observing it for more than 30 years. The control group was 27 healthy relatives of the same people, because they have very close genetic material and live in the same conditions.
It turned out that people with Laron syndrome have less glucose, insulin and creatinine in the blood, lower blood pressure, smaller heart size and thinner walls of the largest arteries (indicating the absence of pathological hypertrophy). The arteries of people with dwarfism also contain less atherosclerotic plaques, despite higher levels of "bad" cholesterol (i.e., that included in low-density lipoproteins).
The result is consistent with what biologists had previously learned about the protective effects of low concentrations of IGF-1, including in experiments on mice. Rodents that served as models of such a genetic abnormality lived 40 percent longer on average.
The new paper confirms that this molecular mechanism can slow aging and the development of late-life diseases. Perhaps in the future its detailed study will help to understand how to extend healthy human longevity without disrupting growth processes.