Causes of heterogeneity in ageing - the Whitehall II study

When the Whitehall II study started in 1985 its aim was to put social class differences in health on the map
and investigate the causes of social inequalities in disease during work life. This it has achieved with
outstanding success. Subsequent to the WHO Commission on Social Determinants of Health, launched by
the Prime Minister in November 2008, Professor Sir Michael Marmot was invited by the Secretary of State
for Health to undertake a national review of the evidence. The Marmot Commission, due to report early in
2010, will propose the most effective strategies for reducing health inequalities in England from 2010 on.
Our current proposal marks a change of direction for the study, namely to combine our existing wealth of
data on social inequalities and chronic disease with new clinical measures of cognitive function, mental
disorders and physical functioning to build Whitehall II into a world-class, interdisciplinary study of ageing.
Ageing is not characterised by universal decline, rather variations in the speed of ageing result in people of
the same age becoming increasingly dissimilar in terms of cognitive, mental and physical health and
functioning over time. Using existing self-reported measures we have shown physical functioning to decline
faster with age in low socioeconomic groups, suggesting that inequalities in functioning will become an
important public health issue as the population ages. Understanding the causes of this age-related individual
heterogeneity and its distribution by social group will be the core focus of our future work. By the proposed
next medical screening, our eleventh wave of data collection, Whitehall II will be optimal for studying
outcomes in the elderly. Ninety percent of participants will be 65+, more than 30% 75-85, and our data will
span an age range of 50 years. In addition to providing insights into individual and social difference in the
development of frailty, disability, dependence, and dementia, our work will enable the determination of
optimal time windows and targets for interventions that lower risk and optimise healthy-ageing and independent living.

Whitehall II is a cohort of 10,308 men and women followed since 1985-88 when they were aged 35-55 and
employed by the Civil Service. It has fulfilled its original aim of understanding the contribution of
psychosocial, behavioural and biological factors to socioeconomic inequalities in health during work-life.
Our current proposal marks a change of direction, namely to build Whitehall II into a world-class,
interdisciplinary study of the determinants of ageing, both individual and socioeconomic.
The main advantage of Whitehall II is that the baseline data collection predates that for most studies of
ageing by 20-30 years. High quality, repeated measures of environmental exposures and pathophysiological
changes over the entire adult life-course bring the advantages of a prospective study of chronic disease
aetiology to the study of ageing. These data, augmented by new measures of cognitive function and mental
disorders at the next sweep, combined with the age profile of the Whitehall II participants at phase 11 (90%
65+, 30% 75-85) provide a study design and cohort optimal for studying outcomes in the elderly.
Ageing is not characterised by ubiquitous decline, rather variations in the speed of ageing result in
contemporaries becoming increasingly dissimilar in terms of cognitive, mental and physical health and
functioning over time. Understanding the causes of this age-related individual heterogeneity and its
distribution by social group will be the core focus of our future work, addressed via three key cross-cutting
aims.
Our first aim is to determine causes of age-related heterogeneity, its origins in midlife and the relative
importance of cumulative exposure to risk factors over the adult life course versus factors predominantly
operating at older ages.
The second aim is to examine biological and behavioural mechanisms underlying age-related heterogeneity in
cognitive, mental and physical health and functioning, and disentangle the temporal relationships, beginning
in midlife, between mental health, cognitive and physical functioning and cardiovascular health.
Our third, longer-term aim for Whitehall II, is to use the findings generated by aims 1 and 2 to build up a
model of the determinants and the mechanisms that generate individual and social heterogeneity in healthy
ageing and its converse; frailty, disability, dependence, and dementia.
Our application requests funding primarily to undertake the phase 11 data collection. In addition we seek
funding to maintain the cohort, prepare for phase 11, contribute to genetic collaborations, and make
Whitehall II data available to the international research community