Live long and prosper: escaping longevity-immunity trade-off

MAKLAKOV_U21DTP

Ageing is one of the big unsolved problems in biology that also affects our everyday life. Ageing reduces resistance to pathogens and old organisms are more likely to die from infectious diseases. Unexpectedly, however, experimental selection for improved immunity in model organisms often results in reduced longevity in the absence of pathogens, while lifespan-extending treatments, such as dietary restriction, impair innate immunity. This longevity-immunity trade-off suggests that some of the most commonly studied compounds with anti-ageing potential, so-called geroprotectors, can make organisms more susceptible to common pathogens.

In this project, you will use the power of the classical model organism in genetics, evolutionary biology and biogerontology – Caenorhabditis elegans nematodes – to investigate how we can escape the longevity-immunity trade-off without paying the price of impaired development or reduced reproductive potential. You will use a variety of genetic and environmental techniques that robustly extend lifespan in C. elegans to test the hypothesis that we can uncouple the benefits of long life from the costs of reduced immunity and reproduction.

The project will capitalize on recent discoveries in the biology of ageing to advance our understanding of one of the fundamental problems in biology – the evolution of ageing and lifespan. The student will receive training in a wide-range of techniques (experimental design, advanced statistical analysis, presentational skills, critical thinking, knowledge transfer, scientific writing, animal culture, microbiology, RNAi gene silencing) that are transferrable to different disciplines as well as job opportunities outside academic research. You will be immersed in the collaborative and supportive research environment and will have the opportunity to work at the interface of evolutionary biology, bio-gerontology and microbiology.

This PhD project is an opportunity to tackle one of the long-standing questions in biology – why do we age – from the unique angle of the intriguing trade-off between longevity and immunity.

References:

Maklakov AA, Chapman T (2019) Evolution of ageing as a tangle of trade-offs: energy versus function. Proc R Soc B, https://doi.org/10.1098/rspb.2019.1604

Lind MI, Ravindran S, Sekajova Z, Carlsson H, Hinas A, Maklakov AA. (2019) Reduced insulin/IGF-1 signalling in adult parents increases offspring fitness. Evolution Letters, 3:207-216

Mautz B, Lind MI, Maklakov AA (2020) Dietary restriction improves fitness of ageing parents but reduces fitness of their offspring. The Journals of Gerontology Series A: Biological Sciences, 75: 843-848