Sex-Specific Gene Expression and Life Span Regulation

Abstract

Aging-related diseases show a marked sex bias. For example, women live longer than men yet have more Alzheimer’s disease and osteoporosis, whereas men have more cancer and Parkinson’s disease. Understanding the role of sex will be important in designing interventions and in understanding basic aging mechanisms. Aging also shows sex differences in model organisms. Dietary restriction (DR), reduced insulin/IGF1-like signaling (IIS) and reduced TOR signaling each increase life span preferentially in females, in both flies and mice. Maternal transmission of mitochondria to offspring may lead to greater control over mitochondrial functions in females, including greater life span and a larger response to diet. Consistent with this idea, males show greater loss of mitochondrial gene expression with age.

Sex differences in the response to dietary restriction in rodents

“…Based on large-scale rodent CR studies in both sexes using multiple hybrid, inbred and recombinant inbred strains showing considerable sex and strain variation in CR-mediated longevity [16,17], it has been proposed that in mice, females respond better to CR [18–20] whilst in rats the opposite is true [20]. However, there are many reported exceptions, making these generalizations unhelpful.…”

“…In the first study, IF initiated in the early phases of autoimmune encephalitis showed protective effects in female mice [47]. However, because only female mice were used in this study, sex-specific responses to DR [21 • ] and/or the etiology and progression of diseases [18] prevent generalization of the finding. In the second study, EOD feeding ameliorated some of the detrimental learning effects and protected against Ab deposition in brains of Alzheimer’s disease (AD) model mice [48].…”

MECHANISMS IN ENDOCRINOLOGY: Lessons from growth hormone receptor gene-disrupted mice: are there benefits of endocrine defects?

“…A reduction in GH action has also been associated with increased cellular stress resistance and mitochondrial health. However, there are sex-specific differences (90,313,314,315) as well as unavoidable tradeoffs in the process. A reduced stature, obesity and possible reduction in reproductive fitness have been associated with studies in the GH deficient and resistant dwarf mouse models (16,316).…”

Sex Differences in Early Embryogenesis: Inter‐Chromosomal Regulation Sets the Stage for Sex‐Biased Gene Networks

“…[11,12] In some cases, sex is a much stronger predictor of risk of or protection from disease than DNA variants. [14] Sex differences are also evident in many complex human traits such as lifespan [15] and aging, [16] brain function, [17][18][19][20] circadian rhythms, [21] cardiovascular structure and function [22] and immunological responses, [6,23] among others. [13] In addition, treatment responses and side effects to drugs for many disorders differ between males and females.…”

“…[13] In addition, treatment responses and side effects to drugs for many disorders differ between males and females. [14] Sex differences are also evident in many complex human traits such as lifespan [15] and aging, [16] brain function, [17][18][19][20] circadian rhythms, [21] cardiovascular structure and function [22] and immunological responses, [6,23] among others. [24,25] The variety of systems exhibiting sexual dimorphisms implies that exploring these differences will afford valuable insights into disease risk and etiology and will lead to more sex-appropriate treatment options.…”