A case study of "disorganized development" and its possible relevance to genetic determinants of aging

Richard F. Walker, Lawrence Pakula, Maxine J. Sutcliffe, Patricia A. Kruk, Jesper Graakjaer, Jerry W. Shay

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)350-356
Number of pages7
JournalMechanisms of Ageing and Development
Volume130
Issue number5
DOIs
StatePublished - May 2009

Fingerprint

Developmental Genes
Proprioception
Digestive System
Telomerase
Telomere
Deglutition
Growth and Development
Chromosome Aberrations
Respiratory System
Tooth
Respiration
Animal Models
Bone and Bones
Mutation
DNA
Brain
Genes

Keywords

  • Aging biomarkers
  • Antagonistic pleiotropy
  • Developmental disorganization
  • Senescence effector genes
  • Senescence regulator genes

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

Cite this

A case study of "disorganized development" and its possible relevance to genetic determinants of aging. / Walker, Richard F.; Pakula, Lawrence; Sutcliffe, Maxine J.; Kruk, Patricia A.; Graakjaer, Jesper; Shay, Jerry W.

In: Mechanisms of Ageing and Development, Vol. 130, No. 5, 05.2009, p. 350-356.

Research output: Contribution to journalArticle

Walker, Richard F. ; Pakula, Lawrence ; Sutcliffe, Maxine J. ; Kruk, Patricia A. ; Graakjaer, Jesper ; Shay, Jerry W. / A case study of "disorganized development" and its possible relevance to genetic determinants of aging. In: Mechanisms of Ageing and Development. 2009 ; Vol. 130, No. 5. pp. 350-356.
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