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Understanding the link between healthy ageing and social interaction


Project Description

Healthy ageing is a priority for all countries since we are living longer than ever before. A number of studies show that social behaviours can prevent some detrimental aspects of aging such as dementia and memory loss. However, the molecular mechanisms by which such behaviours act is unknown. Several social behaviours in mammals such as social cognition, parental behaviours, mating, aggression, and social bonding behaviours are regulated by nuclear receptors. The worm Caenorhaditis elegans is a powerful genetic model whose neural circuitry is well understood and which exhibits social behaviours such as social feeding, parental-offspring interaction and male mating. In addition, C. elegans has approximately 5 times the number of nuclear receptors as mice and humans and many of their functions remain unknown. Some nuclear receptors regulate male mating which, in C. elegans is a stereotypical behaviour that has an initial appetitive component before proceeding to consummatory components. This sequence of appetitive and consummatory components of a complex behaviour governed by both serotonin and dopamine is very similar to that seen in mammals.
We propose to study if differences in sociality seen in mating and feeding behaviour affect different parameters of longevity including the vulnerability to stress, survival and healthy aging process, using the C. elegans model. We will also explore if longevity can predict sociality using different worm strains which have different lifespans. Understanding the complex, potentially reciprocal regulation of ageing and social behaviour is important in devising medications that target signaling pathways involved in the progression of several age-related diseases. In addition, behavioural intervention represents low-cost strategy that can promote healthy aging.
This proposal is unique because it is a novel collaboration combining our expertise in C. elegans genetics and aging (Dr. Kevei) with our knowledge of nuclear receptors and social behaviour (Dr. Vasudevan) to occupy a unique “niche” position in an area of increasing interest i.e. the human healthy aging field. This proposal is of interest to students in several different ways. Students who are interested in cellular signaling could use this system to understand the physiological significance of nuclear receptors in C. elegans. Students who are interested in behaviour/behavioural psychology can modify this project to emphasize the consequences of social behaviours or of stress, while characterizing currently unknown behaviours in several genetic contexts. Finally, this is also interesting to more medically inclined students who would like to explore interventions for aging related diseases such as Alzheimer’s and Parkinson’s disease. Students will use genetic, molecular and behavioural techniques in their study. The student will be part of a vibrant endocrine group at the University of Reading, with an opportunity to get training in teaching pedagogy. In addition, the student will also have an opportunity to network with potential overseas collaborators.

Web links:
https://www.reading.ac.uk/biologicalsciences/about/staff/n-vasudevan.aspx; http://www.reading.ac.uk/biologicalsciences/about/staff/e-g-kevei.aspx

Funding Notes


References

Tawo, R., W. Pokrzywa, E. Kevei, M. E. Akyuz, V. Balaji, S. Adrian, J. Hohfeld and T. Hoppe. ""The Ubiquitin Ligase Chip Integrates Proteostasis and Aging by Regulation of Insulin Receptor Turnover."" Cell 169, no. 3 (2017): 470-482 e13.
Franz, A., E. Kevei and T. Hoppe. ""Double-Edged Alliance: Mitochondrial Surveillance by the Ups and Autophagy."" Curr Opin Cell Biol 37, (2015): 18-27.
Kevei, E. and T. Hoppe. ""Ubiquitin Sets the Timer: Impacts on Aging and Longevity."" Nat Struct Mol Biol 21, no. 4 (2014): 290-2.
Hadjimarkou, M. M. and N. Vasudevan. ""Gper1/Gpr30 in the Brain: Crosstalk with Classical Estrogen Receptors and Implications for Behavior."" J Steroid Biochem Mol Biol 176, (2018): 57-64.
Rainville, J., K. Pollard and N. Vasudevan. ""Membrane-Initiated Non-Genomic Signaling by Estrogens in the Hypothalamus: Cross-Talk with Glucocorticoids with Implications for Behavior."" Front Endocrinol (Lausanne) 6, (2015): 18.
Anchan, D., A. Gafur, K. Sano, S. Ogawa and N. Vasudevan. ""Activation of the Gpr30 Receptor Promotes Lordosis in Female Mice."" Neuroendocrinology 100, no. 1 (2014): 71-80.

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