Antagonistic pleiotropy and the stress theory of aging

Abstract

The ecological stress theory of aging incorporates the normally harsh environments of natural populations and hence restricted resources. Especially towards lethal extremes, positive associations are expected among fitness traits underlain by selection for energetic efficiency favoring genotypes for stress resistance. Positive pleiotropy is therefore expected for fitness traits across varying ages under these conditions. Furthermore, hormetic zones are regions of maximum energetic efficiency, also implying positive pleiotropy. Negative pleiotropy may therefore be mainly a phenomenon of benign environments.

The GH receptor exon 3 deletion is a marker of male-specific exceptional longevity associated with increased GH sensitivity and taller stature

“…This phenomenon could be explained by the positive relationship of GHBP with longevity among AJs, further suggesting the plausibility of a consistent relationship between d3-GHR variation and GH secretion from cellular to organism levels over the life course of individuals. These observations suggest that IGF-1 may exert positive pleiotropy ( 45 ) on many traits associated with healthy longevity. Our observation that IGFBP1 is higher in the d3-GHR subjects suggests that they are more insulin-sensitive ( 46 ).…”

“…Although our study consists of four cohorts with a total of 841 subjects, the sample size ranged from 60 to 600; hence, it is generally low relative to the sample sizes used in many association studies. Mutations in GH-related genes may exert pleiotropic ( 45 ) effects throughout the life span of individuals, which appears to be a universal feature of most if not all major longevity assurance genes. Because IGFs are found across a wide range of organisms and perform similar functions among these, as suggested by Waddington ( 47 ), they could be viewed as “canalized” genes playing a vital role in the survival of organisms across taxa.…”

Endocannabinoids, FOXO and the metabolic syndrome: Redox, function and tipping point – The view from two systems

“…It is likely that most animals have evolved in their 'hormetic zone' where a degree of stress results in optimal fitness (Parsons 2007). 'Mitohormetic' stimuli that result in mitochondrial biogenesis, such as some plant polyphenols, cold, exercise and fasting, are protective and result in improved functional longevity (Tapia 2006).…”

Ecoimmunology: is there any room for the neuroendocrine system?

“…A comprehensive evolutionary interpretation of most age-related changes is offered by the antagonistic pleiotropy theory. (20,(76)(77)(78)(79)(80) This theory assumes that gene variants favorable to survival in young (reproductive) age may become detrimental in old postreproductive age. A possible example is the trade-offs between longevity and infectious diseases.…”