Changing course in ageing research: The Healthy Ageing Phenotype

doi:10.1016/j.maturitas.2009.02.006

Maturitas

Volume 63, Issue 1, 20 May 2009, Pages 13-19

https://doi.org/10.1016/j.maturitas.2009.02.006 Get rights and content

Abstract

Ageing is often associated with the aged and the diseased, nevertheless ageing is a process that starts in-uterus and is characterised by a progressive functional loss but not necessarily by the presence of disease and poor quality of life. How to meander through life without crossing the confines of major chronic disease and cognitive and physical impairment remains one of the most relevant challenges for science and humankind. Delimiting that ‘immaculate’ trajectory – that we dub as the ‘Healthy Ageing Phenotype’ – and exploring solutions to help the population to stay or return to this trajectory should constitute the core focus of scientific research. Nevertheless, current efforts on ageing research are mainly focused on developing animal models to disentangle the human ageing process, and on age-related disorders often providing merely palliative solutions. Therefore, to identify alternative perspectives in ageing research, Unilever and the Medical Research Council (MRC) UK convened a Spark workshop entitled ‘The Healthy Ageing Phenotype’. In this meeting, international specialists from complementary areas related to ageing research, gathered to find clear attributes and definitions of the ‘Healthy Ageing Phenotype’, to identify potential mechanisms and interventions to improve healthy life expectancy of the population; and to highlight areas within ageing research that should be prioritised in the future. General agreement was reached in recognising ageing research as a disaggregated field with little communication between basic, epidemiological and clinical areas of research and limited translation to society. A more holistic, multi-disciplinary approach emanating from a better understanding of healthy ageing trajectories and centred along human biological resilience, its maintenance and the reversibility from early deviations into pathological trajectories, is urgently required. Future research should concentrate on understanding the mechanisms that permit individuals to maintain optimal health when facing pathological hazards and on developing and assessing potential interventions that could aid to re-establish resilience when lost or guarantee its integrity if present. Furthermore it is fundamental that scientific findings are translated incessantly into clear messages delivered to governmental institutions, the industry and society in general.

Introduction

“Prevention is better than cure”
Desiderius Erasmus (1466–1536)

The age distribution of the world's population is dramatically shifting; longevity continues to rise and there are steady improvements in healthcare, but there is not an accompanying increase in fertility rates [1], [2]. In total, the global proportion of people aged above 60 years is expected to increase from 10% to 21% in the next 5 decades [3]. However, research into how to achieve healthy ageing and which life-time trajectories are associated with positive health and wellbeing in older age, is still relatively under-researched. Hence, to identify alternative perspectives in ageing research, Unilever and the Medical Research Council (MRC) of UK convened a Spark workshop entitled ‘The Healthy Ageing Phenotype’ [4]. Spark workshops are strategic meetings in which scientists from different disciplines and perspectives, share knowledge, build novel concepts, and assess options for future research activities. In this particular meeting, international specialists from complementary areas related to ageing research gathered to:

(i)
find clear attributes and definitions of the ‘Healthy Ageing Phenotype’;
(ii)
identify potential mechanisms and interventions to improve healthy life expectancy of the population;
(iii)
highlight areas on ageing research that should be prioritised for the future.

Section snippets

The world is ageing

Global life expectancy in the last two centuries has been increasing linearly and does not appear to be approaching a plateau [2]. Longevity in best in class countries has risen by approximately 3 months per year for the past 170 years and average mean life expectancy is forecasted to be 96.4 years in 2050 [2]. Incessant progress in the prevention of mortality as a result of advances in income, hygiene, sanitation and infection control, nutrition, education, and medicine, is generally believed

The malleability of the ageing process

The recent history of human longevity demonstrates that the ageing process is malleable to a significant degree, but the extent of this has not yet been fully explored in humans as the majority of research on this area has been conducted in lower animal models (e.g., nematodes, flies) with a limited degree of extrapolation [4], [9]. Ageing is a multi-factorial process and it is vital to understand the mechanisms associated with ageing and those that determine healthy life trajectories [10], [11]

Yin and Yang: vulnerability and resilience

It is important to note that ageing over the lifecourse is not necessarily a steady decline from optimal physiological performance in early adulthood to poor functioning in late adulthood. To a large extent, remarkable physiological resilience in early stages of the ageing process reduces the negative effects of external stressors such as smoking, infections, psychological stress, sedentarianism and poor dietary habits and these stressors do not visibly induce morbidities at a young age. By

Ageing and the “Healthy Ageing Phenotype”

Ageing is often defined as the progressive loss of function accompanied by increasing morbidity and decreasing fertility with advancing age [10], [11], [14]. However, although ageing is the most significant risk factor for the appearance of morbidities, the ageing process starts in-uterus and is not necessarily accompanied by the presence of disease and poor quality of life. Life and ageing are practically synonymous and one cannot occur without the other. Unlike ageing, poor health is not a

Once ill always ill? Once frail…

To some extent frailty is the inverse of the Healthy Ageing Phenotype, but the precise extent to which they are two sides of the same coin is as yet unclear. There is no universal definition of frailty, but it is thought to be a multi-factorial dynamic state which occurs as a result of deleterious changes in the homeostatic network [20], [21], [22], [23], [24]. Cumulative defects alter the homeostatic network and lead to multi-system dysregulation and a decline in the adaptive capability to

Multiple tissues but common pathways: mechanisms and biomarkers of the HAP

Many chronic conditions share common underlying pathways and are lifestyle and age dependent (Fig. 1). For example, high-energy intake (diet) with low energy expenditure (physical activity) results in increased visceral obesity, insulin resistance and vascular inflammation. These conditions are associated with loss of metabolic flexibility (i.e., dysregulation of lipid and glucose fluxes), which may lead to CVD, diabetes and neuro-degenerative disease. This metabolic dysregulation is also

A healthy lifestyle the key to healthy senescence

The activities of daily living and lifestyle are very important factors in the maintenance of the homeostatic network. Several studies have demonstrated the health benefits of physical activity and adequate cardio-respiratory fitness [30], [31]. Physical activity has its effect through a variety of mechanisms (e.g., lowering the inflammatory response and positively attenuating several risk factors for CVD), and is associated with decreases in the risk of developing diabetes, CVD and mortality,

On Morpheus arms

Another aspect of a healthy lifestyle is sleep quality and quantity. Although almost one third of human existence is spent sleeping, there is limited evidence about the impact of sleep on ageing. With age, quantity and quality of sleep deteriorates and given that there has been a reduction in the population's total average sleep time over the past 100 years the relative impact of these changes could increase [40], [41]. Among Americans, for example, the modal sleep duration has decreased 1 h

A sound mind in a sound body: wellbeing and health

In addition to studying the physiological homeostasis of the body it is important to understand the psychological determinants that enable people to flourish (i.e., wellbeing) and how this relates to optimal mental and physical functioning. Wellbeing is a complex multi-dimensional concept and there are two main approaches to its study: the eudaimonic approach (also known as psychological wellbeing) centres on the fulfilment of personal potential and living a meaningful life and is concerned

Multi-dimensional problems might need multi-dimensional solutions

The current paper has provided a brief overview of a variety of lifestyle, environmental, psychological and physiological factors that play a role in healthy ageing. What this highlights is that there is not necessarily a single mechanism that underlies healthy ageing, and although there may be common pathways it is important to approach the preservation of the ‘Healthy Ageing Phenotype’ through the implementation of multi-factorial strategies. It may be that the best approach is a combination

Exploring the other side of the moon: a new world demands a change of course

In conclusion, human life expectancy has been increasing linearly and is not expected to stop in the near future [2]. With increases in life expectancy the distribution of the population has changed dramatically and the chances of living to an old age are increasing, but so is the probability of time spent with disease and disability. A new society, with novel characteristics and new needs is emerging and research into healthy longevity requires an innovative approach: multi-factorial

Recommendations

(i)
Ageing over the lifecourse is not necessarily a steady decline from optimal physiological performance in early adulthood to poor functioning in late adulthood. To a large extent, remarkable physiological resilience along the ageing process reduces the negative effects of external stressors such as smoking, infections, psychological stress, sedentarianism, poor dietary habits and alcohol misuse. Further research is required to understand the nature of this resilience and how to prevent permanent

Conflicts of interest

The authors report no conflicts of interest to declare.

Acknowledgements

The authors would like to thank Min-Min Teh, Lucy Boniface and Diana Parry for their collaboration in organising the Spark workshop and Dr. Jonathan Powell, Dr. Joe McNamara, Dr. Mark Pitman and Prof. Stephen Holgate for their valuable comments. The Spark meeting was jointly funded (50/50) by the MRC UK and Unilever Corporate Research.

List of Participants
Dr. Avan Aihie Sayer	Medical Research Council Southampton, UK
Professor Michael Catt	Unilever Corporate Research, UK
Professor Eve van Cauter

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On a global basis, adults 65 years of age and older experience falls more frequently than younger individuals, and these often result in severe injuries as well as increased healthcare costs. Gait and balance disorders in this population are among the most common causes of falls and negatively influence quality of life and survivorship. Although falls are a major public health problem and guidelines/recommendations are available to physicians, many are fully aware of different assessments, tools, and resources available for intervention. Given the risk for potentially devastating outcomes if severe injuries occur secondary to a fall, fall prevention strategies in clinical offices is a timely consideration in today’s health care landscape. This paper presents a three-tier model, comprising assessment, prevention, and intervention, to highlight methods, proactive programs, and innovative tools and technology that have been developed for fall prevention. Awareness of these resources will enhance the clinician’s ability to accurately assess balance and gait, which can improve physical function, and decrease the risk of falls for both average-risk and high-risk older adults.
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Suboptimal sleep patterns predict poorer cognitive function in older adults and induce inflammatory responses. Inflammation could also adversely affect cognitive function. This study explored whether systemic inflammation may be one biological mechanism through which sleep influences cognitive performance. Participants were 4877 men and women from the English Longitudinal Study of Ageing who were followed-up for 8 years starting at wave 4 (2008-09), through wave 6 (2012-13), and until wave 8 (2016–17). Sleep quality and duration were measured with self-reported questionnaires. Cognitive function was assessed objectively with tests of verbal fluency, memory (immediate and delayed recall) and time orientation. Analyses were stratified by sex and adjusted for socio-economic circumstances, health behaviours, limiting long-standing illness, medication, depressive symptoms, and baseline inflammation and cognition. In men, in comparison with optimal sleep duration, short sleep (≤6 h: β = -0.343, C.I. -0.611 to -0.076; >6-7 h: β = -0.263, C.I. -0.506 to -0.020) and long sleep (β = -0.536, C.I. -1.019 to -0.053) measured at baseline predicted lower scores in delayed memory recall at follow-up. In women, sleep duration was unrelated to cognitive performance at follow-up, and in both sexes, there was no relationship between sleep quality and follow-up cognitive performance. There was no evidence of mediating effects of inflammatory markers in the relationship between sleep measures and cognitive performance in both sexes. In conclusion, baseline short and long sleep duration is associated with follow-up cognitive performance in older men, but we found no evidence of any mediating effects of inflammation.

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^☆: Report from a Spark meeting, Amsterdam, May 2007.

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ReviewChanging course in ageing research: The Healthy Ageing Phenotype☆

Abstract

Introduction

Section snippets

The world is ageing

The malleability of the ageing process

Yin and Yang: vulnerability and resilience

Ageing and the “Healthy Ageing Phenotype”

Once ill always ill? Once frail…

Multiple tissues but common pathways: mechanisms and biomarkers of the HAP

A healthy lifestyle the key to healthy senescence

On Morpheus arms

A sound mind in a sound body: wellbeing and health

Multi-dimensional problems might need multi-dimensional solutions

Exploring the other side of the moon: a new world demands a change of course

Recommendations

Conflicts of interest

Acknowledgements

Curr Biol

Arch Gerontol Geriatr

Am J Clin Nutr

Sleep Med Rev

J Psychosom Res

Am J Prev Med

Demography. Broken limits to life expectancy

Science

Ten commandments for the future of ageing research in the UK: a vision for action

BMC Geriatr

Census 2001: CD supplement to the National report for England and Wales and key statistics for local authorities in England and Wales

The World Health Report: 2003: shaping the future

Geographical variation in life expectancy at birth in England and Wales is largely explained by deprivation

J Epidemiol Commun Health

Puzzles, promises and a cure for ageing

Nature

Why do we age?

Nature

Mechanisms of ageing: public or private?

Nat Rev Genet

Evidence of genetic enrichment for exceptional survival using a family approach: the Leiden Longevity Study

Eur J Hum Genet

The evolutionary genetics of ageing and longevity

Heredity

The heritability of human longevity: a population-based study of 2872 Danish twin pairs born 1870–1900

Hum Genet

How heritable is individual susceptibility to death? The results of an analysis of survival data on Danish, Swedish and Finnish twins

Twin Res

Fetal and infant growth and impaired glucose tolerance at age 64

BMJ

The intrauterine environment as reflected by birth size and twin and zygosity status influences insulin action and intracellular glucose metabolism in an age- or time-dependent manner

Diabetes

Metabolic aspects of insulin resistance in individuals born small for gestational age

Horm Res

From bedside to bench: research agenda for frailty

Sci Aging Knowledge Environ

Review
Changing course in ageing research: The Healthy Ageing Phenotype☆