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

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

doi:10.1016/j.mad.2009.02.003

Cited by 18 publications

(12 citation statements)

References 34 publications

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“…According to the epigenetic clock method, blood tissue from these cases is age appropriate. These findings are consistent with leukocyte telomere measurements in our first case [1]. Incidentally, leukocyte telomere length captures another dimension of aging and is at best weakly correlated with DNAm age after correcting for chronological age [12, 13].…”

Section: Discussionsupporting

confidence: 89%

“…We previously reported the unusual case of a teenage girl stricken with multifocal developmental dysfunctions including bilateral hip dislocations, abnormal brain development, tracheomalacia, gastro-intestinal disorders and dysmorphic features [1, 2]. In addition to these problems, her physical and functional development was dramatically delayed resulting in her appearing to be a toddler or at best a preschooler, even unto the occasion of her death at the age of 20 years (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

“…The case was not part of this study. Credits: Reproduced with kind permission from the publisher of [1]. …”

Section: Introductionmentioning

confidence: 99%

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Epigenetic age analysis of children who seem to evade aging

Walker¹,

Liu

Peters

et al. 2015

Aging

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We previously reported the unusual case of a teenage girl stricken with multifocal developmental dysfunctions whose physical development was dramatically delayed resulting in her appearing to be a toddler or at best a preschooler, even unto the occasion of her death at the age of 20 years. Her life-long physician felt that the disorder was unique in the world and that future treatments for age-related diseases might emerge from its study. The objectives of our research were to determine if other such cases exist, and if so, whether aging is actually slowed. Of seven children characterized by dramatically slow developmental rates, five also had associated disorders displayed by the first case. All of the identified subjects were female. To objectively measure the age of blood tissue from these subjects, we used a highly accurate biomarker of aging known as “epigenetic clock” based on DNA methylation levels. No statistically significant differences in chronological and epigenetic ages were detected in any of the newly discovered cases.Our study shows that a) there are multiple children who maintain the façade of persistent toddler-like features while aging from birth to young adulthood and b) blood tissue from these cases is not younger than expected.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

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Epigenetic age analysis of children who seem to evade aging

Walker¹,

Liu

Peters

et al. 2015

Aging

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“…31 During the course of her life, multiple examinations failed to support a diagnosis of any known genetic syndrome or chromosomal abnormality, yet she persists in a condition resembling that expected to result from damage to genes controlling developmental inertia. In fact at 18 years old she still appears physically as an infant (Fig.…”

Section: Testing the Theorymentioning

confidence: 99%

“…31 Phenotypically, she appears to be an infant despite the fact that she is now 18 years old. Furthermore, tissues in her body are aging at different rates as if they were independent elements and not part of a unit organism.…”

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confidence: 99%

Developmental Theory of Aging Revisited: Focus on Causal and Mechanistic Links Between Development and Senescence

Walker¹

2011

Rejuvenation Research

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Senescence violates the most basic tenet of natural selection by causing death rather than individual survival. Thus, current theories favor the concept of antagonistic pleiotropy (AP) to explain how aging emerged in metazoans. Presumably, pleiotropic genes reduce vigor and limit longevity in adults. However, they also promote fitness and reproduction in juveniles, causing them to be selected and retained in the gene pool. The general hypothesis presented herein is a special case of AP that identifies the common cause and mechanism of aging in iteroparous (i.e., capable of reproducing multiple times) animals. It ascribes senescence to unremitting, nonprogrammed change or remodeling forced upon the adult soma by postmaturation expression of developmental gene(s) affecting dynamic transformation of the single-celled conceptus into a complex, multicellular organism. Whereas persistent somatic change is necessary for development to proceed normally, it also has the potential to erode homeostasis in adults after maturation is complete. Thus, developmental inertia is the primary cause of senescence, whereas decay of internal order and integrated function among interdependent systems of the body is the general mechanism by which aging progresses over time. Accordingly, this global pathogenic process creates an environment in which the many recognized, age-associated physiologic and metabolic sequelae can arise as consequences of senescence rather than causes of it. Paradoxically, the genes that promote somatic remodeling essential for development and survival also guarantee aging and death by the same action whose outcomes differ only by the time it is expressed relevant to maturation.

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Bovine Prospection, the Mesocorticolimbic Pathways, and Neuroethics: Is a Cow’s Future Like Ours?

Comstock

2020

Advances in Neuroethics

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

Cited by 18 publications

References 34 publications

Epigenetic age analysis of children who seem to evade aging

Epigenetic age analysis of children who seem to evade aging

Developmental Theory of Aging Revisited: Focus on Causal and Mechanistic Links Between Development and Senescence

Bovine Prospection, the Mesocorticolimbic Pathways, and Neuroethics: Is a Cow’s Future Like Ours?

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