Current Projects

Effect of maternal age on lifespan and fecundity in Brachionus manjavacas. width=

Effect of maternal age on lifespan and fecundity in Brachionus manjavacas.  (A) Survivorship and fecundity of maternal generation.  Offspring hatched on days 3, 5, 7, and 9 of the F0 (red arrows) were collected to measure F1 lifespan (B) and fecundity (C).  Offspring lifespan and fecundity declined significantly with increasing maternal age.

Biology of Aging: Mechanisms and evolutionary conservation of therapeutic interventions

Therapies to improve health and increase lifespan rely on plasticity in life history. Limiting food intake, also known as caloric restriction (CR), is one of the most reliable means of extending lifespan in a variety of animals, yet the evolutionary origins and genetic mechanisms behind the response to CR are poorly understood. To determine the degree of conservation of responses to beneficial therapies, we investigated lifespan and fecundity changes in response to a variety of levels of CR among 12 strains of the rotifer Brachionus plicatilis isolated from different environments. The level of lifespan extension was different between sexual and asexual individuals of the same species. Interestingly, the degree of lifespan extension under CR was inversely correlated with lifespan under food-replete conditions. Differences in reproduction under varied CR regimens, even when lifespan extension was similar, suggested that different types of CR extend lifespan through diverse genetic mechanisms. Ongoing projects include analysis of differential gene expression over the rotifer life cycle and comparing gene expression in isolates with different responses to caloric restriction to identify genes involved in lifespan extension, using RNA-Seq.  Additionally, we are testing the conservation of other lifespan-extending interventions, including the genetically-mediated response to low temperature.
 
 

Biology of Aging:  Maternal effects

Juvenile rotifer with fluorescent labeling of mitochondria, examined by confocal microscopy. Reproductive and ciliated locomotory tissues have high levels of mitochondria. Mitochondrial dysfunction may contribute to early aging in the offspring of older mothers. Image by E. Corey

Juvenile rotifer with fluorescent labeling of mitochondria, examined by confocal microscopy. Reproductive and ciliated locomotory tissues have high levels of mitochondria. Mitochondrial dysfunction may contribute to early aging in the offspring of older mothers. Image by E. Corey

Phenotypic plasticity may occur not only in an individual, but also across generations. Transgenerational phenotypic plasticity, known as a “maternal effects,” occurs when the maternal response to the environment causes a change in offspring phenotype without a change in the genome. While many studies have focused on the detrimental effects on progeny of advanced maternal age and harmful prenatal environments, little is known about the role of beneficial maternal inheritance on aging.

The Gribble lab investigates the effects of maternal age and maternal CR on the lifespan and healthspan of Brachionus manjavacas offspring. With increasing maternal age, lifespan, health, and fecundity of female offspring decreases significantly. Interestingly, maternal CR partially rescues these effects, increasing the mean lifespan and fecundity of female offspring, even when those offspring are not directly exposed to CR.  These findings point to the exciting possibility that beneficial maternal environments may have a positive effect on offspring aging, perhaps over multiple generations.

Protoperidinium steidingerae isolated from the Atlantic Ocean, south of Martha’s Vineyard.  Protoperidinium are single cell, heterotrophic dinoflagellates with complex life cycles; they occupy a unique position in the trophic dynamics of the plankton in marine systems, as they consume phytoplankton larger than themselves.  Photo credit: Kristin Gribble.

Protoperidinium steidingerae isolated from the Atlantic Ocean, south of Martha’s Vineyard. Protoperidinium are single cell, heterotrophic dinoflagellates with complex life cycles; they occupy a unique position in the trophic dynamics of the plankton in marine systems, as they consume phytoplankton larger than themselves. Photo credit: Kristin Gribble.

We are investigating not only changes in phenotype and gene expression, but also the epigenetic changes associated with maternal age and maternal CR, and how these may transgenerationally alter gene expression in metabolic and repair pathways, leading to changes in offspring lifespan and healthspan. Epigenetic modifications—changes to DNA that regulate the activity of specific genes but not the underlying nucleotide sequence—play an active role in aging and are a likely mechanism for the transmission of maternal effects to offspring. Epigenetic mechanisms that regulate chromatin structure include DNA methylation and histone modifications such as methylation, acetylation, ubiquitination, phosphorylation, ADPribosylation, and sumoylation. The time scale of epigenetic histone modification allows phenotypic plasticity within a 1–3 generation window, and is thought to have evolved to deal with frequent environmental change, such as food level fluctuations, periodic hypoxia, and temperature shifts. Parental nutrition and stress impact the epigenetic profiles of subsequent generations and influence offspring metabolism, immune function, mental health, and behavior in humans and mammal model systems. Understanding the influence and mechanisms of maternal effects on aging will provide fertile ground for future research and for development of therapies to improve human health during aging.
 
 

Biological Oceanography

Dr. Gribble has studied the ecology, molecular phylogeny, and life history of marine dinoflagellates (single cell aquatic protists), including harmful algal bloom phytoplankton and heterotrophic dinoflagellates. She described the relationship between the molecular phylogeny and morphological taxonomy of an important and widespread genus of heterotrophic dinoflagellates, Protoperidinium, and described the group’s biogeography off the western coast of Ireland. Dr. Gribble provided the first description of the life history, including sexual and asexual reproduction, of two species of Protoperidinium. The lab looks forward to continuing work on environmental regulators of life history strategy in marine phytoplankton.

Print Friendly