Turning green in healthy ageing: exploration of novel seaweed compound in cognitive performance

Established Supervisor: A/Prof Francesca Fernandez <Francesca.Fernandez@acu.edu.au>
Emerging Supervisor: Prof. Lyn Griffiths (external)

Project Description

With a demographic shift toward an ageing population, dementia is becoming a growing public health concern worldwide. Alzheimer’s disease (AD), the most common form of dementia, affects over 55 million individuals in the world, with an estimated 10 million new cases per year. Symptoms of AD vary throughout disease progression, starting from a preclinical phase (with apparition of amyloid plaques in the brain and inflammation in brain) to mild and moderate memory impairment. Both memory impairment and inflammation are also present during healthy ageing. In our previous genetic study, genetic markers in the DNA (molecule carrying all genes) in a case control cohort for AD, have been reported significantly associated with cognitive performance in both AD patients and healthy aged individuals (aged average 78 years old). These genetic markers were present in specific genes called Sirtuin (SIRT), able to modulate the chromatin.  The chromatin corresponds with how the DNA (carrying all the genes from an individual) will be compacted or in a more relaxed form in the nucleus of the cells. This will have an effect on how some genes will be turned active or no (like a light switch).

SIRT proteins modulate many aspects of chromatin biology, such as genome stability but as well play a critical role in major biological functions such as cell survival, metabolism, cardiovascular function, ageing and memory.  In ageing context, SIRT levels in the brain have been reported lower when compared to younger adults in a previous study. Increasing evidence have reported the critical roles of SIRT proteins in both health and pathological conditions such as cancer and neurodegenerative diseases. Several randomized controlled trials have demonstrated that some modulating factors are able to change the levels of SIRT proteins in human samples, impacting major physiological function. For instance, SIRT inhibitors have been considered in the treatment of several types of cancer while SIRT activators were suggested as therapeutic targets for age-related disorders such as AD. Resveratrol, a stilbene subclass of phenolic compounds, found in several plants, including grapes, blueberries, raspberries, and peanuts, has been previously reported increasing SIRT activity in human cells. When tested in clinical trial, resveratrol improves cognitive function; however, it does appear to have significant adverse effects (for 2.5 g) such as nausea, vomiting, diarrhea and liver dysfunction when administered for several days. Consequently, it is important to continue searching for AD treatment with limited adverse effects. 

Ulvan, is a sulfated polysaccharide extracted from Ulva green seaweed species [18]. Ulvan supplements have been reported to possess significant biological properties, such as antioxidant, anti-inflammatory and  anti-hyperlipidemic. Interestingly, ulvans can increase levels of SIRT 1 in human cell lines. Furthermore, sulfated xylorhamnoglucuronan, or “SXRG 84” supplement (extracted from ulvans) has been previously shown to decrease levels of inflammation in a human double blind clinical trial setting with no adverse effects reported.

Research gap: Interest in natural therapy and recent findings on the implication of SIRT protein in ageing have led to considering the potential of seaweed supplement for modulating the levels of SIRTs. Considering that seaweed supplement (SXRG 84) has been already administered safely to human (in the context of obesity) and that green seaweed can increase the levels in SIRT in human cells, we will test the effects of SXRG 84 administration in a pilot cohort of healthy adult older adults for 6 weeks and investigate the effects of this intervention on memory performance (cognitive tests) and peripheral markers for SIRT and inflammation (ethics submitted). By addressing the cognitive aspects of ageing, our society can better support older adults in maintaining autonomy and their participation to activities in our community.

Description of the research internship opportunity

The honours student involved in this proposal will acquired a large range of new skills as she will be involved in the testing of participants, saliva collection and analysis of peripheral tissues collected. More specifically, healthy aged adults (n= 10 in total, aged over 65, same percentage of male (n=5) and female (n=5)) English speaker and considered in good health (no diagnosed condition)  will be invited to attend research lab (for saliva sample and blood collection) and perform memory testing tested at baseline (prior starting treatment) and at 7 weeks follow up at ACU, Brisbane campus.  Previous research project has used the same type of cognitive battery tests in Alzheimer’s Disease patients and healthy elderly cohorts. Both peripheral tissues (saliva and blood collected by supervisor) will be further analysis for comparison of levels of Sirtuin (SIRT) and inflammatory markers measured and which peripheral tissues reflect the best our previous work in human brain.  The analysis of the samples will occur at the Institute of Health and Biomedical Innovation (IHBI)  in a research lab led by Prof. Lyn Griffiths (co-supervisor). The honours student will be trained for current methodology used in proteomics in the research lab (including Western Blot, Nanodrop, colorimetric essays). 

In addition, the honours student will be trained to deliver cognitive testing including Mini- Mental State examination (MMSE, assessment of global functioning), National Adult Reading Test (NART, testing working memory), Rey Auditory Verbal Learning (Recall memory), Controlled Oral Word Association Test (COWAT, testing of verbal fluency), Digit Span (working memory and executive function), Digit Symbol Coding (assessment of processing speed) and Boston Naming Test and  Clock Drawing Task (spatial memory). The SXRG 84 supplement (Sulfated xylorhamnoglucuronan-rich extract) has already been prepared by our industry partner Venus Shell System Pty Ltd (NSW) who will be part in future grant application and supervision of HDR student in the future. The supplement will be mixed with food (2g/day) by participant and be administrated for 6 weeks (as per previously published study). Improvement of cognitive performance and increase of SIRT levels of activity and their levels in saliva and blood, are expected to be observed in the participants after SXRG 84 supplementation.

This innovative project will provide an essential proof of concept evidence of our research paradigm and design prior to progressing to future clinical trials and grant application (Medical Research Future Funding, Dementia scheme) including AD patients in 2025. 

Altogether, the honours student will acquire multi-disciplinary research skills, at ACU and at IHBI, offering training on cutting-edge research equipment.  It will also contribute to provide training  for a driven student who will undertake a Ph.D in 2026. The honours student will participate to critical produce data for a pilot study, which will be published in high rank journal (Molecular psychiatry journal) participating not only to research excellence at ACU but as well as potentially impacting positively vulnerable community (by providing natural ways of improving their memory).

This honours work performed in 2025 will be included in a pilot study (and later on clinical trial)  to test the same compound in a cohort of AD patients in a Ph.D project in 2026. This multidisciplinary  Ph.D will occur in collaboration with Industry Partner Venus Shell Systems (NSW) and collaborator Prof. Lyn Griffiths from IHBI (Queensland University of Technology). 

This translational research project will benefit not only the honours student but also the multidisciplinary research at ACU, supported by industry partner.