Aging, Immunity and Obesity


Researchers: Fleur Ponton, Fiona Clissold, Samantha Solon, Shawn Wilder, Stephen Simpson

The longevity and rate of aging of animals can vary substantially within and among species. While caloric or dietary restriction have long been hypothesized to affect aging, there is growing evidence that the macronutrient content of an animal’s diet can have a large effect on longevity and aging. In particular, several recent studies in our laboratory have shown that several species of arthropods survive significantly longer when fed high carbohydrate diets relative to high protein diets. Current and future work in the lab is aimed at examining the role of dietary macronutrients for the longevity and aging of a range of other animals to determine if this is a general pattern and the mechanisms responsible for this effect.

  • Piper MDW, Partridge L, Raubenheimer D, and Simpson SJ. 2011. Dietary restriction and aging: a unifying perspective. Cell Metabolism 14:154-160.
  • Simpson SJ, and Raubenheimer D. 2009. Macronutrient balance and lifespan. Aging 1:875-880.
  • Maklakov AA, Simpson SJ, Zajitschek F, Hall M, Dessman J, Clissold FJ, Raubenheimer D, Bonduriansky R, and Brooks RC. 2008. Sex-specific fitness effects of nutrient intake on reproduction and lifespan. Current Biology 18:1062-1066.
  • Lee KP, Simpson SJ, Clissold FJ, Brooks R, Ballard JWO, Taylor PW, Soran N, and Raubenheimer D. 2008. Lifespan and reproduction in Drosophila: new insights from nutritional geometry. Proceedings of the National Academy of Sciences, USA 105:2498-2503.
  • Simpson SJ, and Raubenheimer D. 2007. Caloric restriction and aging revisited: the need for a geometric analysis of the nutritional bases of aging. Journals of Gerontology A: Biological Sciences. 62:707-713.


Researchers: Alison Gosby, Lindsey Gray, Samantha Solon, Stephen Simpson

A significant contributor to the rising rates of human obesity is an increase in energy intake. The protein leverage hypothesis proposes that a dominant appetite for protein in conjunction with a decline in the ratio of protein to fat and carbohydrate in the diet drives excess energy intake and could therefore promote the development of obesity. In a randomised controlled experimental study we have recently shown that lean humans eat significantly more carbohydrate and fat in order to maintain protein intake when percent protein of the diet is reduced from 15 to 10%. The results suggest that any change in the nutritional environment that dilutes dietary protein with carbohydrate and fat will promote overconsumption and encourage weight gain. Unfortunately there are many factors in the current nutritional environment encouraging us to eat foods that are high in sugars and fats, including reduced cost and increased availability of these foods and underpinning all this is our ancestral environment in which fat and simple sugars were highly prized; leaving us with a predilection for these foods.

Key Publications:

  • Gosby AK, Conigrave AD, Lau NS, Iglesias MA, Hall RM, Jebb SA, Brand-Miller J, Caterson ID, Raubenheimer D, and Simpson SJ. 2011. Testing protein leverage in lean humans: a randomized controlled experimental study. PLoS ONE 6:e25929.
  • Gosby AK, Soares-Wynter S, Campbell C, Badaloo A, Antonelli M, Hall RM, et al. 2010. Design and testing of foods differing in protein to energy ratios. Appetite 55:367-70.
  • Brooks RC, Simpson SJ, and Raubenheimer D. 2010. The price of protein: combining evolutionary and economic analysis to understand excessive energy consumption. Obesity Reviews 11:887-894.
  • Simpson SJ, and Raubenheimer D. 2009. The protein leverage hypothesis in human obesity. Cardiology in General Practice 10:32.
  • Simpson SJ, and Raubenheimer D. 2005. Obesity: the protein leverage hypothesis. Obesity Reviews 6:133-142.


Researchers: Fleur Ponton, Robert Graham, Tamara Pulpitel, Stephen Simpson

Nutrition is critical to immune defence and resistance to pathogens, with consequences that affect the health, welfare and reproductive success of individual organisms, and also has profound ecological and evolutionary implications. In humans, under-nutrition, notably of protein, is a major contributor to morbidity and mortality due to infectious diseases, particularly in the developing world. Likewise, over-nutrition and its associated metabolic disorders may impair immune function, disrupt the relationship with symbiotic and commensal microbiota, and increase susceptibility to infectious disease. Despite the undoubted importance of nutrition to immune defence, the challenge remains to capture the complexity of this relationship. The prospect of our research is to study the network of relationships between food dietary composition, immunity, gut microbiota and disease. Describing the network of interactions underlying nutritional immunology is essential to provide a more comprehensive and robust understanding of the key determinants of the outcome of host-pathogen interactions. The Geometric Framework provides a powerful organising framework for achieving such a synthesis.

Key Publications:

  • Ponton F, Wilson K, Cotter SC, Raubenheimer D, and Simpson SJ. 2011. Nutritional immunology: a multi-dimensional approach. PLoS Pathogens 7:e1002223.
  • Ponton F, Lalubin F, Behm C, Wilson K, and Simpson SJ. 2011. Hosts use altered macronutrient intake to circumvent parasite-induced reduction in fecundity. International Journal for Parasitology 41:43-50.
  • Cotter SC, Simpson SJ, Raubenheimer D, and Wilson K. 2011. Macronutrient balance mediates trade-offs between immune function and life history traits. Functional Ecology 25:186-198.
  • Povey S, Cotter SC, Simpson SJ, Lee KP, and Wilson K. 2009. Can the protein costs of bacterial resistance be offset by altered feeding behaviour? Journal of Animal Ecology 78:437-446.
  • Lee KP, Simpson SJ, and Wilson K. 2008. Dietary protein-quality influences melanization and immune function in an insect. Functional Ecology 22:1052-1061.
  • Lee KP, Cory JS, Wilson K, Raubenheimer D, and Simpson SJ. 2006. Flexible diet choice offsets protein costs of pathogen resistance in a caterpillar. Proceedings of the Royal Society B 273:823-829.