A case study of "disorganized development" and its possible relevance to genetic determinants of aging.
In 1932, Bidder postulated that senescence results from "continued action of a (genetic) regulator (of development) after growth ceases (maturation occurs)." A 16-year-old girl who physically appears to be an infant has not been diagnosed with any known genetic syndrome or chromosomal abnormality. The subject's anthropometric measurements are that of an 11-month-old. Coordinated development of structures for swallowing/breathing has not occurred resulting in dysfunctional digestive and respiratory systems. Brain structure, proprioception and neuroendocrine functions are infantile. Dental and bone ages are pre-teen, while telomere length and telomerase inactivity suggest a cellular age at least comparable to her chronological age. Sub-telomeric microdeletions known to be responsible for developmental delay and chromosomal imbalances are not present. Findings suggest that the subject suffers from "developmental disorganization" resulting from spontaneous mutation of Bidder's putative "regulator" of development, thereby providing an opportunity to locate and identify developmental gene(s) responsible for ensuring integrated and coordinated change in form and function from conception to adulthood. If their continued expression beyond maturation erodes internal order to promote senescence then further study of her DNA and testing of homologous genes in animal models may provide clues to genetic determinants of aging and human life span.
University of South Florida College of Medicine, Tampa, FL, United States. drrwalker@gmail.com
Richard F
RF
Walker
Lawrence C
LC
Pakula
Maxine J
MJ
Sutcliffe
Patricia A
PA
Kruk
Jesper
J
Graakjaer
Jerry W
JW
Shay
D000293:Adolescent; D041923:Adolescent Development; D000375:Aging / Q000235:genetics*; D002658:Developmental Disabilities / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D011859:Radiography; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000201:enzymology / Q000235:genetics
D019098:Telomerase