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LIFEPATH Report Summary

Project ID: 633666
Funded under: H2020-EU.3.1.1.

Periodic Reporting for period 1 - LIFEPATH (Lifecourse biological pathways underlying social differences in healthy ageing)

Reporting period: 2015-05-01 to 2016-10-31

Summary of the context and overall objectives of the project

In the last century, evidence has emerged that socio-economic have an important impact on health and on the quality of ageing. Subjects belonging to lower socio-economic (SES) strata have shorter life expectancy and poorer quality of life (disability) compared to those from higher SES. There are several open questions emerging from descriptive data that apply virtually to all nations:

1) Are relative differences or absolute differences across SES strata relevant to the understanding of the phenomenon and to policies?
2) What is the role of SES on health and premature mortality when compared to the standard United Nations/WHO 25x25 risk factors such as smoking, alcohol, overweight, etc. What is the respective mediating role played by the traditional United Nations/ WHO 25x25 risk factors, as opposed to SES – that go beyond risk factors – such as psycho-social stress, infections, professional exposures, etc…?
3) What are the best indicators (simple and composite) that allow the investigation of the impact of SES on health (e.g. mortality vs functional outcomes)?
4) What are the intermediate biological mechanisms that link low SES with health impairment?

We have shown that the impact of low SES on premature mortality is comparable to that of major UN/WHO 25x25 risk factors. We are also exploring several potential pathways with the use of biomarkers and omic technologies, and in particular epigenetic changes. We have started analyzing the role of the epigenetic clock (“age acceleration” related to changes in methylation patterns in selected DNA regions) and suggested that methylation age “accelerates” more quickly in low SES individuals, thus confirming the existence of basic biological mechanisms that can be potentially reverted.

From the policy angle, the knowledge we produce will be able to confirm alternative policy models. For example, in our life-course model of ageing it is clearly emerging that early life experiences (including low SES) have a lasting impact on the prospects of healthy ageing later in life.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

"In the reporting period of the project we have achieved significant goals:

1) A paper based on 48 cohorts from different continents, showing that the impact of SES on mortality holds after careful adjustment for UN/WHO 25x25 risk factors has been accepted by the Lancet.

2) A number of papers have already been published and others are in various stages of preparation or submission. The following papers have been published:

a. Castagné R, Delpierre C, Kelly-Irving M, Campanella G, et al. A life course approach to explore the biological embedding of socioeconomic position and social mobility through circulating inflammatory markers. Scientific Reports 6, 27:2016, 25170

b. Barboza Solís C, Fantin R, Castagné R, Lang T. et al. Mediating pathways between parental socio-economic position and allostatic load in mid-life: Findings from the 1958 British birth cohort. Social Science & Medicine, 165, 2016, 19-27.

c. Petrovic D, Pivin E, Ponte B. et al. Sociodemographic, behavioral and genetic determinants of allostatic load in a Swiss population-based study. Psychoneuroendocrinology, 67, 2016, 76-85.

d. Barboza Solís C, Fantin R, Kelly-Irving M, Delpierre, C. Physiological wear-and-tear and later subjective health in mid-life: Findings from the 1958 British birth cohort. Psychoneuroendocrinology,74,2016,24-33.

e. Lopez –Arana S, Avendano M, Forde I, van Lenthe FJ and Burdorf A. Conditional cash transfers and the double burden of malnutrition among children in Colombia: a quasi-experimental study. Br J Nutr. 2016 May, 115(10):1780-9.

f. Lopez –Arana S, Avendano M, Forde I, van Lenthe FJ and Burdorf A. The impact of a conditional cash transfer programme on determinants of child health: evidence from Colombia. Public Health Nutr. 2016 Oct, 19(14):2629-42.

Papers in press:
• Castagné R, Kelly-Irving M, Campanella G, Guida F, Krogh V, Palli D, Panico S, Sacerdote C, Tumino R, Kleinjans J, de Kok T, Kyrtopoulos S, Lang T, Stringhini S, Vermeulen R, Vineis P, Delpierre C, Chadeau-Hyam M. Biological marks of early-life socioeconomic experience is detected in the adult inflammatory transcriptome. Scientific Reports (in press).

• Stringhini S. Carmeli C. et al. Socioeconomic status and the 25x25 risk factors as determinants of premature mortality: a multi-cohort study of 1.7 million men and women. In Press. The Lancet.

Papers submitted:
• Harmonization of SES indicators in LIFEPATH (D’Errico et al. Submitted Journal PLoS ONE)
• Socio-Economic Differences in Children's Growth Trajectories from Infancy into Early Adulthood: Evidence from four European countries. Submitted to the Journal of Epidemiology and Community Health.
• Socioeconomic differentials in children’s height growth from infancy to early childhood, (Lead TCD, with University of Porto, UCL, University of Turku, Imperial College): paper submitted to the Journal of Epidemiology and Community Health.
• The biology of inequalities in health: the LIFEPATH project. Paper submitted to BMC Public Health Journal.

3) We have performed complex work of data centralization including signature of DTAs and harmonization of variables from the cohorts, towards the creation of a stable database.
4) We have collected administrative data (including on ageing) and data from social surveys that encompass a wealth of SES variables and risk factors for disease from 20 European nations (these are administrative or survey data in addition to the cohorts mentioned above).
5) Metabolomic data and biomarkers have been acquired for a large number of cohorts to study the metabolic impact of SES and its mediating role in influencing ageing patterns.
6) New methylation analyses (Illumina 850K) for about 1,000 samples from the TILDA cohort, has been statistically analyzed and a paper is in preparation.
7) A workshop is currently being organized in London (February 2017) led by UCL to discuss the policy implications of early findings."

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Overall, a complex and articulate picture is emerging suggesting that SES exceeds the role of UN/WHO 25x25 risk factors, and this is partly explained by the imprinting left by other exposures including psycho-social stress on epigenetic “age acceleration”. This has clear policy implications. We are also comparing and testing different policy approaches, particularly the Conditional Transfer Programmes such as the one held in New York that is currently being analyzed at King’s College for its impact on health. Similar programmes are under way in Colombia, Bangladesh and Italy and we have created a network across them to harmonize the collection of ageing and health data.

If the project is successful, it will allow us to build a socio-biological model of the impact of low SES on (unhealthy) ageing, to identify intermediate biomarkers that allow the monitoring of the effectiveness of interventions such as CCT, and to generate evidence to support competing intervention models (e.g. focused on infancy, middle-age or late life).

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