1. Social differences in Healthy Ageing: the LIFEPATH project Lifepath: Life-course biological pathways underlying social differences in healthy ageing Paolo Vineis Imperial College London

2. Lifepath Objectives: To show that healthy ageing is an achievable goal for society, as it is already experienced by individuals of high socio-economic status (SES). To improve the understanding of the mechanisms through which healthy ageing pathways diverge by SES, by investigating life- course biological pathways using omic technologies. To examine the consequences of the current economic recession on health and the biology of ageing (and the consequent increase in social inequalities). To provide updated, relevant and innovative evidence for healthy ageing policies (particularly “health in all policies”)

3. To achieve these objectives we will use data from three categories of studies: 1. Europe-wide or national surveys combined with population registry data 2. Cohorts with intense phenotyping and repeat biological samples (total population >33,000) 3. Large cohorts with biological samples (total population >202,000). 4. Metabolomics, gene methylation and transcriptomics will be performed

4. The life-trajectory model of ageing (David Blane) implies a «build-up» phase and a «decline» phase

6. Years of life lost (preliminary, Stringhini et al manuscript in preparation) MEN WOMEN

7. Behavioral factors and social inequalities in health Stringhini et al. Contribution of modifiable risk factors to social inequalities in type 2 diabetes: prospective Whitehall II cohort study. BMJ 2012; 345.

8. Genome (G = DNA) Transcriptome (R = RNA) Proteome (P = large molecules) Metabolome (M = small molecules) Transmission of conserved quantities is transmission of information via molecules (=the internal exposome). The exposome concept refers to the totality of environmental exposures from conception onwards. The internal exposome is based on measurements in biological material of complete sets of biomarkers of exposure, using repeated biological samples especially during critical life stages.

9. SES and immune system biomarkers Alley et al. Socioeconomic status and C-reactive protein levels in the US population: NHANES IV. Brain Behav Immun. 2006 Sep;20(5):498-504 NHANES IV

10. Methylation as a marker of socio-economic differentials Methylation as a marker of socio-economic differentials in EPIC-Italy (Stringhini et al, IJE 2015) Effect sizes of the association between RII (as index of SES) and Age Acceleration (AA). EPIC Italy (A) and MCCS cohort (B).

11. Conditional Cash Transfer (CCT) Government programs that transfer cash to poor families on condition that they make investments in human capital: ▫ Sending children to school regularly ▫ Taking children to regular health and nutrition check ups Two broad objectives: –Short-term: support household consumption/income protection –Mid- to long-term: accumulate human capital and break the intergeneration transmission of poverty Specific objectives depend on the defined sector goals (e.g., schooling, health status, nutrition)

12. CCT programmes: 2008 World Bank, 2009 NYC: 1 st CCT in a high-income country!

13. Lopez, Avendano, Van Lenthe, Burdorf 2015 Impact of Familias CCT Programme on conditioned behaviours VariablesAll Healthcare services use a 1.85 (1.03, 3.30)* Growth and development checks frequency b 1.17 (0.62, 1.71) Registered in growth and development program a 4.34 (2.51, 7.53) * Mother´s attendance to workshops a 2.36 (1.42, 3.92) * Diarrhea Mother´s attendance to workshops on: Prenatal care2.92 (1.74, 4.89) * Nutrition workshops1.33 (0.84, 2.11) Infection workshops2.57 (1.44, 4.60) *

14. Collaborators Lifepath (WP leaders) Rotterdam University - Johan Mackenbach Lausanne University - Silvia Stringhini HuGeF - Silvia Polidoro, Giovanni Fiorito ICL - Marc Chadeau-Hyam KCL - Mauricio Avendano Toulouse University - Michelle Kelly Irving UCL - Michael Marmot, Mika Kivimaki Zadig - Luca Carra