Ageing as a Risk Factor for Disease Teresa Niccoli, Linda Partridge  Current Biology  Volume 22, Issue 17, Pages R741-R752 (September 2012) DOI: 10.1016/j.cub.2012.07.024 Copyright © 2012 Elsevier Ltd Terms and Conditions

Figure 1 Disease or total death rates for the most common diseases of old age. (A) Cardiovascular disease incidence in England in 2006 (source: British Heart Foundation ‘Coronary heart disease statistics’ 2010). (B) Dementia prevalence in EU countries in 2006 (source: Alzheimer Europe, 2009). (C) Age-specific mortality rates per 100,000 population, UK (source: Cancer Research UK). Current Biology 2012 22, R741-R752DOI: (10.1016/j.cub.2012.07.024) Copyright © 2012 Elsevier Ltd Terms and Conditions

Figure 2 Nutrient-sensing pathways. Illustration of nutrient-sensing pathways' responses to nutritional signals and how they interact with each other. Dotted arrows represent negative feedback interactions between the pathways. Upon insulin/IGF binding, insulin-like receptors signal via the Insulin Receptor Substrate (IRS) to Akt to inhibit FOXO and stimulate the glucose transporter (GluT) to allow glucose import. Amino acids stimulate TOR via TSC1/TSC2 inhibition to down-regulate autophagy and promote translation via S6K and 4EBP. ATP levels modulate AMPK, which can promote autophagy and also interacts both with the IIS and TOR pathways. In a number of organisms there are multiple paralogue copies of insulin-like receptors, IRS, FOXO and GluT, but for simplicity only one is depicted. Current Biology 2012 22, R741-R752DOI: (10.1016/j.cub.2012.07.024) Copyright © 2012 Elsevier Ltd Terms and Conditions

Figure 3 DNA repair in disease development. Diagram of the contribution of DNA damage repair to the development of disease. (A) By inducing senescence and apoptosis in cardiomyocytes, DNA damage repair contributes to heart disease. (B) Triggering cell cycle re-entry contributes to neurodegeneration; (C) but when working efficiently blocks cancer development. Current Biology 2012 22, R741-R752DOI: (10.1016/j.cub.2012.07.024) Copyright © 2012 Elsevier Ltd Terms and Conditions

Figure 4 Current therapies target individual diseases in isolation; therapies targeted to the ageing process itself aim to cover many diseases simultaneously. Current Biology 2012 22, R741-R752DOI: (10.1016/j.cub.2012.07.024) Copyright © 2012 Elsevier Ltd Terms and Conditions