Ageing Medicine

Non-invasive neuroimaging measurements combined with physiological, neurocognitive and biota-based biomarker measurements as predictors of health outcome in ageing 

PI: Prof. Balazs Gulyas​

Age-associated disability and diseases are placing a growing burden on society, in general. In Singapore, in particular, these issues are now-a-days in the fore due to the fast ageing of the Singaporean society and the rapid increase of age-related disorders, including dementias.

A better understanding of the ageing process, with special regard to the ageing of the brain, would help us prepare protective and preventive strategies as well as treatments to slow down the pathological ageing process, thereby decrease both individual and societal burdens. Hence, markers of the underlying biological ageing process are needed to help identify people at increased risk of age-associated physical and cognitive impairments and ultimately, death.

For this reason the search for early predictive biomarkers indicating normal versus pathological ageing, in general, and brain ageing, in particular, is in the forefront of ageing research. Recently, non-invasive structural neuroimaging approaches have shown significant advancements in this field and some of the findings indicate firmly that non-invasively obtained neuroimaging biomarkers can provide us with reliable and predictive information about the person’s “brain age”, progression of ageing, and mortality (Cole et al., Brain age predicts mortality, Molecular Psychiatry, 2017 Apr 25. doi: 10.1038/mp.2017.62).

The above study has indicated that a brain-predicted age, indicative of an older-appearing brain, is associated with weaker grip strength, poorer lung function, slower walking speed, lower fluid intelligence, higher allostatic load

and increased mortality risk. Furthermore, the combination of brain-predicted age and DNA-methylation-predicted age improves mortality risk prediction and thus can provide us with a strong predictor of health outcomes. Consequently, the combination of distinct measurements of biological ageing, including non-invasive neuroimaging, helps to determine risk of age-related deterioration and death.

The present projects aims at introducing the neuroimaging protocols of the aforementioned UK study, together with the introduction of complimentary biomarker measurements (including neurocognitive, physiological, and biome measurements) in a Singaporean cohort of healthy ageing people with an eye on identifying early predictive biomarkers of normal and pathological ageing and developing a protocol for screening larger populations in the future.

Exercise Medicine as a core strategy for ageing health: Bridging the evidence-gaps between Community and Clinical Exercise Programmes for chronic disease prevention and treatment in older population

PI: Prof. Fabian Lim

This strategic initiative aims to translate the current evidence on exercise medicine for clinical applications in age associated musculoskeletal conditions (i.e., osteoporosis, sarcopenia and frailty) by demonstrating the value of community exercise programmes in preventing, delaying and moderating age-related decline in musculoskeletal health. Specifically, this study aims to compare musculoskeletal health biomarkers of older men and women who have been performing aerobic, calisthenics or mixed-exercise programmes in community settings. A secondary aim is to contribute to the current debates on clinical definition and measurements of sarcopenia and frailty.

This study will recruit male and female participants (> 50 years of age) who have been participating for > 2years in community-based programmes for aerobic exercise (AE, running and brisk walking), callisthenic exercise (CE, Tai Qi Quan and gym exercises) or mixed aerobic and callisthenic exercises (MAC, exercises dance classes). Up to 50 participants will be recruited from each exercise group after obtaining their informed-consent. Another n=50 sedentary participants will be recruited to form the Control Group (CG), making a total of up to n=200 participants in the study

Each participant will attend the trial once in a fasted state to under the following measurements and procedures: Anthropometry: Height, weight, body mass index, waist and hip circumference, peripheral, central and total body fat and bone density at lumbar and hip region using the DXA. Physical Performance: hand grip strength, isometric strength, 20 m walking speed, balance test, flexibility test, Frenchey index, sit-up-and-go test, bean bag throw. Frailty and Sarcopenia Assessment;

Modified Fried frailty phenotype, FRAIL questionnaire, Rockwood Clinical Frailty Scale, SARCF questionnaire.

Survey: Demographic, health history, exercise habits, 24h dietary recall, food frequency questionnaire, medication and dietary supplements, occupation history, menstrual pattern (women only). Cognitive Assessment: Psychomotor vigilance test for reaction time, vigilance, and pattern recognition, Montreal Cognitive Assessment (MoCA).

Venous blood samples (15 mL) will be collected for measurement of blood lipids, fasted blood glucose, HbA1c, inflammatory cytokines, hormonal profile, blood count, and calcitonin. Some blood will be stored for future analysis of myostatin, brain neurotrophic factors, DNA damage, metabolomics and lipidomics. Stool, urine, saliva and sputum samples will also be collected and stored for future analyses.

Optional assessments: the participants will also have the option to undertake the 7-day physical activity profile and the aubmaximal treadmill walking test for those without history of heart disease, uncontrolled blood sugar level and blood pressure < 142/100. ​

Functional food based gut microbiome engineering: an approach toward healthy lifespan extension

PI: Prof. Schuldnt

Gut microbiota has been suggested to play an important role in inflammation and muscle strength. There is also evidence that frailty is associated with chronic inflammation and muscle strength. Therefore, changes in the gut microbiome could play an important role in the development of frailty, the biggest problem in ageing. Recently, in a few Caucasian studies, a gut microbiome profile has been characterized to have prominent associations between fraility. It was found that frailty was negatively associates with gut microbiota diversity, and associated with certain species and genus abundance. To improve the quality of life and empower the ageing community with active and independent life styles, we intend to determine microbiota profiles associated with reduced muscle strength and inflammatory responses in ageing Singaporeans. We will then identify dietary supplements which can modulate the profile of the microbiota to be consistent with the profile of healthy subjects.

The information on microbiota associated with muscle strength will utilize data and stool samples from our on-going study of microbiota of male ageing cohorts and the study submitted to ARISE by Sven Pettersson, entitled, Exercise adapted microbiome: a novel approach to sustain health and support healthy ageing for Singaporeans, to be conducted using female cohorts. In addition, inflammatory responses triggered by the various stool samples will be evaluated in vitro. An in vitro microcosm to simulate the intestine will be established using stool samples from the various subjects. Microcosms will be seeded with probiotic strains know to down regulate inflammation and modulate the intestinal microbiota, alone and in combination with supplements, including curcumin. Combinations will be identified which can restore an undesirable microbiota profile to that associated with better muscle strength and less inflammation. It is envisaged that dietary supplements will aid in maintaining or restoring a microbiota associated with health.