Life Sciences Research for Lifelong Health

Olivia Casanueva

Research Summary

Groundbreaking work in the nematode Caenorhabditis elegans has demonstrated that ageing is not simply a stochastic and progressive decay, but that it is genetically controlled by the longevity pathways. Strikingly, lifespan is highly variable even in genetically identical individuals reared under controlled environmental conditions.

We are interested in finding the mechanisms underlying transcriptional inter-individual variability in genes that modulate lifespan and determining to what extent it explains individual-to-individual differences in the rates of ageing. We are also interested in studying the influence of both stochastic and environmental variability during early life and its long-term effect on health. Dietary restriction (DR), reduced food intake without malnutrition, increases health and function during ageing and protects against ageing-related disease in most organisms. We are interested in understanding how early life nutrition (and DR) can set rates of ageing via epigenetic mechanisms.

Answering these questions requires the development of new technologies that make whole animals centre stage and will have a significant conceptual impact on ageing research and personalized medicine.  

Latest Publications

Epigenetic inheritance of proteostasis and ageing.
Li C, Casanueva O

Abundant evidence shows that the genome is not as static as once thought and that gene expression can be reversibly modulated by the environment. In some cases, these changes can be transmitted to the next generation even if the environment has reverted. Such transgenerational epigenetic inheritance requires that information be stored in the germline in response to exogenous stressors. One of the most elusive questions in the field of epigenetic inheritance is the identity of such inherited factor(s). Answering this question would allow us to understand how the environment can shape human populations for multiple generations and may help to explain the rapid rise in obesity and neurodegenerative diseases in modern society. It will also provide clues on how we might be able to reprogramme the epigenome to prevent transmission of detrimental phenotypes and identify individuals who might be at increased risk of disease. In this article, we aim to review recent developments in this field, focusing on research conducted mostly in the nematode Caenorhabditis elegans and mice, that link environmental modulators with the transgenerational inheritance of phenotypes that affect protein-folding homoeostasis and ageing.

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Essays in biochemistry, 60, 1744-1358, 191-202, 2016

PMID: 27744335

Niche-associated activation of rac promotes the asymmetric division of Drosophila female germline stem cells.
W Lu, MO Casanueva, AP Mahowald, M Kato, D Lauterbach, EL Ferguson

Drosophila female germline stem cells (GSCs) reside adjacent to a cellular niche that secretes Bone Morphogenetic Protein (BMP) ligands and anchors the GSCs through adherens junctions. The GSCs divide asymmetrically such that one daughter remains in the niche as a GSC, while the other is born away from the niche and differentiates. However, given that the BMP signal can be diffusible, it remains unclear how a local extracellular asymmetry is sufficient to result in a robust pattern of asymmetric division.

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PLoS biology, 10, 7, e1001357, 2012

PMID: 22802725
DOI: 10.1371/journal.pbio.1001357

Fitness trade-offs and environmentally induced mutation buffering in isogenic C. elegans.
MO Casanueva, A Burga, B Lehner

Mutations often have consequences that vary across individuals. Here, we show that the stimulation of a stress response can reduce mutation penetrance in Caenorhabditis elegans. Moreover, this induced mutation buffering varies across isogenic individuals because of interindividual differences in stress signaling. This variation has important consequences in wild-type animals, producing some individuals with higher stress resistance but lower reproductive fitness and other individuals with lower stress resistance and higher reproductive fitness. This may be beneficial in an unpredictable environment, acting as a "bet-hedging" strategy to diversify risk. These results illustrate how transient environmental stimuli can induce protection against mutations, how environmental responses can underlie variable mutation buffering, and how a fitness trade-off may make variation in stress signaling advantageous.

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Science (New York, N.Y.), 335, 6064, 82-5, 2012

PMID: 22174126
DOI: 10.1126/science.1213491

Group Members

Latest Publications

Epigenetic inheritance of proteostasis and ageing.

Li C, Casanueva O

Essays in biochemistry
60 1744-1358:191-202 (2016)

PMID: 27744335

Fitness trade-offs and environmentally induced mutation buffering in isogenic C. elegans.

MO Casanueva, A Burga, B Lehner

Science (New York, N.Y.)
335 6064:82-5 (2012)

DOI: 10.1126/science.1213491

PMID: 22174126

Neuronal signaling modulates protein homeostasis in Caenorhabditis elegans post-synaptic muscle cells.

SM Garcia, MO Casanueva, MC Silva

Genes & development
21 22:3006-16 (2007)

DOI: 10.1101/gad.1575307

PMID: 18006691

Germline stem cell number in the Drosophila ovary is regulated by redundant mechanisms that control Dpp signaling.

MO Casanueva, EL Ferguson

Development (Cambridge, England)
131 9:1881-90 (2004)

DOI: 10.1242/dev.01076

PMID: 15105369

At least two receptors of asymmetric acetylcholinesterase are present at the synaptic basal lamina of Torpedo electric organ.

OI Casanueva, P Deprez, T García-Huidobro

Biochemical and biophysical research communications
250 2:312-7 (1998)

DOI: 10.1006/bbrc.1998.9303

PMID: 9753626