In order to design impactful interventions that can maximise the length of time that a person is healthy, we must first understand fundamental research about the biology of ageing.
by Dr Anis Larbi
The world’s population is rapidly ageing – according to forecasts by the World Health Organization (WHO), the proportion of the world's population that is over 60 years old will double from about 11 per cent to 22 per cent between 2000 and 2050. Over the same period, the absolute number of people aged 60 years and over is expected to increase from 605 million to 2 billion.
With this expected increase in the number of elderly in our societies, most concerns are centred on chronic or debilitating conditions often associated with ageing. These conditions may reduce autonomy in the elderly and ultimately lead to a lower quality of life, plus put a burden on healthcare systems. However, with advancements in R&D related to ageing, my team and I believe it will be possible to introduce impactful interventions that maximise healthspan and positively transform the experience of ageing for Singaporeans and others worldwide.
Fundamental biological research in ageing has become more essential than ever. We need to understand the ageing process better so that we can implement effective social and healthcare policies to prolong a better quality of life. My team in Singapore has been very interested in studying the immunological and biological capacities in healthy ageing as well as for individuals with co-morbidities (frailty, diabetes, dementia, heart diseases, metabolic syndrome). We have a “Biology of Ageing” programme at A*STAR’s Singapore Immunology Network (SIgN) that also examines the effects of specific interventions on the ageing process. I would like to share some of our recent findings in the Singapore context.
Impact of Ageing on Singapore
In Singapore, the proportion of residents aged 65 years and above has increased from 8.5 per cent in 20072 to 13 per cent in 2017 . This figure is expected to reach 25 per cent by 2030 . This situation requires attention as ageing populations typically face major health, societal and economic challenges.
However, when we consider ageing from the perspective of longevity, we have good news. Singapore has made successful advancements in public health, medicine, science, and technology, that enable Singaporeans to live longer, more productive lives. We can positively transform the experience of ageing if we are able to deliver impactful interventions to lessen or prevent the illnesses or disabilities associated with old age. For this to happen, we first need to understand the biology of healthy ageing.
Key findings of the SG90 Longevity Cohort and the SLAS-2 Longitudinal Cohort Studies
The SG90 Longevity Cohort Study, launched in 2015, is an initiative by A*STAR and the National University Health System (NUHS) to study a cohort of approximately 1,000 elderly individuals in Singapore aged 90 years old and above. The aim is to select those with the best health status as a model of successful ageing, identifying biomarkers and signatures for healthy ageing and longevity, be it genetics, diet or lifestyle factors.
Preliminary findings from the SG90 study have yielded interesting observations, such as gender difference as a factor in healthy ageing. SG90 researchers found that Singaporean men appear to be healthier in old age compared to Singaporean women, as they are less likely to have impaired cognition (30 per cent in men versus 39 per cent in women). The men are also more likely to be independent in their activities of daily living (47 per cent in men versus 34 per cent in women). Initial results also indicate that more men have a positive outlook on their health, and are less depressed or anxious compared to women. As the study continues, the SG90 researchers hope to uncover the reasons for this gender difference as a factor in healthy ageing, to understand whether it stems from educational differences, family support, or other considerations. The hope is to eventually reverse the gender disparity by introducing intervention measures that will allow both men and women to live their best lives.
A*STAR is also involved in another cohort study termed the second Singapore Longitudinal Ageing Study (SLAS-2) alongside the National University of Singapore (NUS). This study commenced in 2009 and involves 3,200 Singaporean men and women aged 55 and above. Through the study, we have identified a population of immune cells that does not show signs of ageing – what we call “resistance to senescence”. These T-cells are important for fighting infections such as tuberculosis, as well as diseases like cancer. By studying this population of cells, we can potentially isolate the factors that lead to ageing resistance, and find ways to harness these factors to slow down the body’s overall ageing process. The possibilities are indeed exciting.
This study also demonstrated the relationship between two conditions: cognitive impairment and physical frailty with inflammation.
We discovered key inflammatory markers associated with frailty, an age-related condition characterised by slowness and fatigue, amongst other symptoms. The condition of frailty is not well understood, and clinical assessments of frailty can be subjective. With the discovery of these inflammatory markers in the immune system, we hope to introduce and popularise a more objective assessment of frailty based on biological markers. This has also led to studies on whether the onset of age-related diseases like dementia could be more definitively linked to the perturbation of the immune system caused by things like infections.
We are currently tapping on the Frailty Intervention Trial (FIT) as part of the SLAS-2 study to analyse the biological aspects of frailty reversal. The idea behind FIT was to better predict the onset of frailty, and reduce the problems associated with frailty in the long term, such as falls and hospitalisations. 250 elderly males and females in the frail category, aged 65 to 89 years old, were recruited for FIT. Lifestyle interventions included a dedicated dietary regime with specific nutritional supplements, tailored physical exercise, and cognitive stimulation programmes. We followed up with the participants after six and 12 months of interventions, and discovered that such a multi-intervention approach was indeed beneficial for combating frailty.
Further analysis of the results also indicate that metabolic regulations in the body are at the centre of one major component of frailty – sarcopenia, or age-related loss of muscle mass and strength. This suggests the need to pay attention to factors that affect metabolic regulations, especially in the elderly, such as food intake and glucose levels, amongst other things.
With these discoveries from ageing-related R&D, you can see that practical solutions can be found, and impactful interventions designed, to slow down ageing and help the elderly maintain their functional capabilities so that they can age with dignity and have a better quality of life. This way, societies will benefit from their wealth of experiences contributed to the younger generations, and the lessened burden on healthcare and other social systems. Investing in the biological aspects of ageing and intervention studies is the way to go forward. Most of the research funding has been dedicated to developing supporting solutions for an ageing society, it is time to prevent these conditions from appearing.
It is a great time to be alive and a great time to study ageing.
- Xu W, Larbi A. Markers of T Cell Senescence in Humans. Int J Mol Sci. 2017 Aug 10;18(8)
- Fulop T, Witkowski JM, Le Page A, Fortin C, Pawelec G, Larbi A. Intracellular signaling pathways: Targets to reverse immunosenescence. Clin Exp Immunol. 2017 Jan;187(1):35-43
- Lu Y, Tan CT, Nyunt MS, Mok EW, Camous X, Kared H, Fulop T, Feng L, Ng TP, Larbi A. Inflammatory and immune markers associated with physical frailty syndrome: findings from Singapore longitudinal aging studies. Oncotarget. 2016 May 17;7(20):28783-95
- Fülöp T, Dupuis G, Witkowski JM, Larbi A. The Role of Immunosenescence in the Development of Age-Related Diseases. Rev Invest Clin. 2016 Mar-Apr;68(2):84-91
- Gao Q, Camous X, Lu YX, Lim ML, Larbi A, Ng TP. Novel inflammatory markers associated with cognitive performance: Singapore Longitudinal Ageing Studies. Neurobiol Aging. 2016 Mar;39:140-6
Dr Anis Larbi is the principal investigator, Singapore Immunology Network (SIgN) at the Agency for Science, Technology and Research (A*STAR).