Longevity Questions

Study of the Phenotype of "Abnormal" Fibroblasts

80. How do the gene signature, metabolism, and general condition of fibroblasts actively producing elastic material differ from "healthy" or "young" fibroblasts?

Benefit: Understanding this phenotype can help develop methods to "switch" aging fibroblasts to the correct, regenerative pathway, while avoiding the activation of unwanted, pathological programs.

Analysis of "Defects" in Elastotic Material

81. What is the exact structure and biomechanical properties of abnormal elastic material?

82. Why is it often fragmented?

83. What types of crosslinks are prevalent?

Benefit: A detailed analysis of the defects will indicate which aspects (correct crosslinking, protection from fragmentation, interaction with microfibrils) need special attention when developing methods to restore functional elastin.

Thus, elastosis can be considered as a "failed experiment" of nature in restoring elastic structures. By studying the reasons for this failure at the molecular and cellular level, we can learn important lessons to ensure that our "therapeutic experiment" in elastin rejuvenation is successful.

Transhumanism in a Distant City, [03.05.2025 06:06]
Based on the information about the evolution of the extracellular matrix (ECM) and elastin, a number of interesting and important questions arise:

84. What were the very first molecules that performed the functions of the primitive ECM in unicellular ancestors of animals or in the earliest stages of multicellularity?

85. What minimal components of the ECM and cellular receptors for them are absolutely necessary for a stable transition to a multicellular organization?

86. How did the evolution of ECM composition and complexity go hand in hand with the evolution of cellular adhesion mechanisms (e.g., cadherins), ECM receptors (integrins), and intracellular signaling, including mechanotransduction?

87. What was the precise evolutionary advantage of the emergence of the basement membrane?

88. How did its emergence influence the ability to form specialized tissues and organs?

89. What specific genetic events (gene duplications, exon shuffling, mutations in regulatory regions) led to the emergence of a functional elastin gene (ELN) specifically in the jawed vertebrate lineage?

90. From which ancestral gene did it most likely descend?

91. What were the unique physiological requirements or pre-existing molecular features (e.g., ECM composition, enzyme systems) in early vertebrates that created the selective pressure and/or opportunity for the evolution of elastin-mediated elasticity rather than the development of alternative systems as in invertebrates?

92. How exactly were ancient matrix proteins (fibrillins, fibulins) and enzymes (LOX/LOXL) "co-opted" to assemble the complex structure of elastic fibers?

93. What changes in these proteins were key to their new role?

94. How inevitable was the emergence of elastin to provide aortic and lung functions in vertebrates?

95. Could evolution have found other molecular solutions (e.g., modified resilin) ​​if genetic or environmental conditions had been different?

96. Was the emergence of elastin associated with certain evolutionary "trade-offs" or vulnerabilities?

97. Are hereditary diseases associated with defects in elastin or fibrillin (e.g., Cutis Laxa, Marfan syndrome) an inevitable consequence of the complexity of this system?

98. Are there examples of vertebrate groups that, in the course of their subsequent evolution and adaptation, have secondarily lost the elastin gene or significantly changed the structure and role of elastic fibers?

99. If so, how did this affect their physiology?

100. Is the rate of accumulation of damage in the ECM (collagen cross-linking, elastin degradation) simply the result of physicochemical processes and biochemical constraints, or could it be an evolutionarily "tuned" characteristic associated with the lifespan strategy of the species (e.g., in long-lived species, selection was directed toward a more stable matrix)?

101. What specific adaptations in ECM genes or ECM repair/renewal systems allow species with negligible senescence or long lifespans to maintain a functional matrix much longer than humans?

These questions highlight that ECM and elastin are not simply static components, but products of long-term evolution, the study of which can provide deep insights into their function, pathology, and potential avenues for intervention.