Longevity Questions

Control of Secretion and Transport

42. Does the structure and dynamics of the actin cytoskeleton (especially cortical actin) influence the exocytosis of vesicles containing tropoelastin and accessory proteins, directing them to specific sites on the membrane?

43. Does the actin cytoskeleton participate in the formation or stabilization of "pores" or secretion sites on the plasma membrane?

Experimental Evidence

44. How does the process of elastogenesis (localization, orientation, assembly efficiency) change when various components of the actin cytoskeleton are experimentally disrupted (e.g., by using inhibitors of actin polymerization such as cytochalasin D, inhibitors of myosin II type blebbistatin, or inhibitors of the Rho/ROCK signaling pathways that regulate the cytoskeleton)?

45. What do high-resolution imaging techniques (e.g., correlative light and electron microscopy) reveal about the spatial relationship between actin structures and elastin assembly sites?

Transhumanism in a Distant City, [03.05.2025 03:24]
To determine which method of stimulating elastin synthesis is the safest, most effective, and most controllable, a number of comparative questions need to be answered for each of the proposed approaches (AAV/LNP gene therapy, mRNA delivery, small molecules, cell therapy)

Level and Functionality

46. Which technology provides the greatest increase in the synthesis of functional (properly assembled and cross-linked) elastin in target cells (e.g., skin fibroblasts or vascular smooth muscle cells)?

47. Is there evidence that any method promotes not only synthesis but also better assembly?

Duration of Action

48. How long is the action time of each approach?

49. How transient is the effect of mRNA delivery (days/weeks)?

50. How long can expression be maintained in AAV therapy (months/years)?

51. Do small molecules require chronic administration?

52. How long do implanted cells survive and function in cell therapy?

Achieving the Therapeutic Threshold

53. Is the level of elastin enhancement achieved by each method sufficient to produce a significant therapeutic or rejuvenating effect in tissue?

Immunogenicity

53. Which approach elicits the least immune response?

54. How immunogenic are AAV capsids?

55. Lipid nanoparticles (LNPs)?

56. Elastin protein itself when overexpressed?

57. Implanted cells (especially allogeneic)?

Genotoxicity/Mutagenesis

58. What is the risk of integration of a viral vector (even AAV has minimal risk) or other genetic constructs into the host cell genome, which could lead to mutations or activation of oncogenes?

59. Are there risks associated with DNA contamination in mRNA products?

Off-target Effects:

60. How specific is the delivery for each method?

61. What is the risk that gene therapy, mRNA, or small molecules will affect off-target cells/tissues when administered systemically, causing unwanted elastin synthesis or other side effects?