Biology subjects

Hoekstra, L. A.

Publications and source records attributed to Hoekstra, L. A..

3 recordsLinked to original sources

bioRxiv2025

Sex- and age-differences in cellular hallmarks of aging in a species with female-biased longevity and environmental sex determination

Cellular hallmarks of aging have been discovered and characterized in a number of model species for studying aging biology - such as humans, mice, fruit flies, and nematodes. Whether these canonical age-related changes to cellular physiology are present across diverse species that have variable rates of demographic aging remains less studied. Here, we tested whether several ubiquitous cellular hallmarks of aging - mitochondrial function, reactive oxygen species generation, and inducible DNA damage - change with age and in a sex-dependent manner in a species with indeterminate growth and reproduction (painted turtles, Chrysemys picta). A further feature of their biology that recommends them for an ecological model of vertebrate aging is their female-biased longevity, despite an absence of genotypic sex determination. Thus lifespan and aging may be reliable features of sex-specific life-histories. We measured aspects of mitochondrial health (cellular basal, maximal, and spare oxygen consumption rates), cellular levels of reactive oxygen species, and aspects of DNA damage and repair from exposure to UVB. We used these measures across several physiological axes as proxies for age-related physiological dysfunction. We further assessed our measures across several populations of painted turtles. We found that sex explained the largest proportion of variation, with males differing from females in mitochondrial function, reactive oxygen species production, and inducible DNA damage. In several cases, age significantly interacted with sex, but the effect size was small relative to sex alone. Thus, we found that sex, rather than age or size, was a consistent predictor of cellular aging physiological in this species with where females live longer and age slower.

physiology↗

bioRxiv2025

Widespread sex-biased gene expression reflects female-biased longevity in a species with environmental sex determination

Sexes frequently differ in life history traits including body size, lifespan, and age at sexual maturity. Aging, the progressive decline in physiological function and cellular resilience over time, is a central process contributing to sex-specific life histories, yet the mechanisms driving sex differences in aging remain largely unresolved. Long-term mark-recapture efforts revealed a striking pattern of female-biased longevity in the painted turtle (Chrysemys picta), a species with temperature-dependent sex determination. As a result, this species provides a compelling system to examine the mechanisms of sex-specific aging in the absence of sex chromosomes. Here, we characterize sex- and age-associated patterns in the blood transcriptomes of wild painted turtles (n = 93). We identified widespread gene expression differences between females and males (2,347 genes; 13.4% of all filtered genes). In contrast, only six genes showed significant linear relationships with continuous age in both sexes. We also employed a machine learning approach which identified distinct sets of genes for which expression was predictive of age in each sex. Age-related gene expression patterns highlight both conserved molecular pathways with known roles in aging as well as novel gene targets. These findings suggest sex-specific molecular processes underlie sex-biased demographic aging and raise questions regarding the environmental and developmental drivers of sex-biased gene expression.

ecology↗

bioRxiv2017

Energy demand and the context-dependent effects of genetic interactions

Genetic effects are often context dependent, with the same genotype differentially affecting phenotypes across environments, life stages, and sexes. We used an environmental manipulation designed to increase energy demand during development to investigate energy demand as a general physiological explanation for context-dependent effects of mutations, particularly for those mutations that affect metabolism. We found that increasing the photoperiod during which Drosophila larvae are active during development phenocopies a temperature-dependent developmental delay in a mitochondrial-nuclear genotype with disrupted metabolism. This result indicates that the context-dependent fitness effects of this genotype are not specific to the effects of temperature and may generally result from variation in energy demand. The effects of this genotype also differ across life stages and between the sexes. The mitochondrial-nuclear genetic interaction disrupts metabolic rate in growing larvae, but not in adults, and compromises female, but not male, reproductive fitness. These patterns are consistent with a model where context-dependent genotype-phenotype relationships may generally arise from differences in energy demand experienced by individuals across environments, life stages, and sexes.\n\nIMPACT SUMMARYGenetic effects on traits are often context dependent, such that a genotype that improves fitness under one context may have no effect or even a deleterious effect in another context. The external environment is a common context that affects the degree to which a genotype determines a phenotype, but the internal environment of an organism (e.g., its genetic background, sex or life stage) also provides an important context that may modify the phenotypic expression of a genotype. Here we combine new data on the phenotypic effects of a well-characterized genetic interaction between the mitochondrial and nuclear genomes of the fruit fly Drosophila with prior observations to support a model of energy demand as a general explanation for context-dependent genetic effects, particularly for mutations that affect metabolism. We show that the magnitude of fitness effects of this genetic interaction correlates positively with the degree of energy demand among developmental treatments that accelerate growth rate, across developmental stages that differ in the cost of growth, and between sexes with potentially different costs of reproduction. These internal and external contexts create variable demands on energy metabolism that will impact the efficacy of natural selection acting on metabolic mutations in populations.

evolutionary biology↗