Longevity Questions

Transhumanism in a distant city, [03.05.2025 08:13]
To go further, we need to make one big clarification:

The most well-known hereditary diseases associated with defects in key proteins of elastic fibers - fibrillin-1 and elastin: Marfan syndrome and the Cutis Laxa (Flabby skin) group of diseases.

1. Marfan Syndrome (MFS)

* Genetic Defect: Caused by mutations in the FBN1 gene, which encodes the protein Fibrillin-1.

* The role of Fibrillin-1: This is a large glycoprotein, which is the main component of extracellular microfibrils. Microfibrils perform two important functions:

* Serve as a framework ("reinforcement") on which the protein tropoelastin is deposited during the formation of mature elastic fibers.

* Bind and sequester (keep inactive) growth factors, particularly transforming growth factor beta (TGF-β).

Disease Mechanism: Defective fibrillin-1 results in:

* Structural weakness: Malformed microfibrils and, as a result, defective elastic fibers make connective tissue weak and less elastic.

* Excessive TGF-β signaling: Defective microfibrils bind TGF-β less well, its concentration in tissues increases, which causes abnormal cellular signaling and contributes to some manifestations of the disease, especially widening (aneurysm) of the aorta.

* Pattern of Inheritance: Autosomal dominant (one copy of the mutant gene from one of the parents is enough). Characterized by high penetrance (carriers of the mutation almost always have manifestations), but very variable expressivity (the degree and set of symptoms vary greatly even within the same family).

Clinical Manifestations: Affects multiple organ systems:

* Skeletal system: Tall stature, long limbs and fingers (arachnodactyly), joint hypermobility, spinal deformities (scoliosis, kyphosis), chest deformities (sunken or chicken chest), flat feet.

* Visual system: Ectopia lentis (displacement of the lens of the eye) is a classic sign. Also characteristic are high myopia, increased risk of retinal detachment, early development of glaucoma and cataracts.

* Cardiovascular system: The most serious and life-threatening manifestations. Dilation (aneurysm) of the root and ascending aorta with a high risk of aortic dissection. Mitral valve prolapse, aortic and mitral valve insufficiency.

* Pulmonary system: Increased risk of spontaneous pneumothorax (collapsed lung), emphysema-like changes.

* Skin: Atrophic striae ("stretch marks") on the shoulders, back, thighs, not associated with weight change. Tendency to hernias.

* Nervous system: Dural ectasia (stretching of the dura mater of the spinal cord).