With expanding ageing populations throughout the world, research efforts to promote healthy ageing has shown that biomarkers are linked to the ageing process and age-related disease manifestation. Thus, providing potential for supplementation of biomarkers to mitigate diseases and encourage healthy ageing.
by Deborah Emmanuel Seah Qing En
"The rapidly ageing population presents the biggest healthcare challenge of this century. Put simply, it is the climate change of healthcare. Unless, we refocus healthcare practice on prevention and keep the ageing population healthy for longer, the economic impacts of the demographic shift will be almost insurmountable."
Dr Brian Kennedy
It is estimated that by the year 2050, one in four people living in Asia Pacific will be over 60 years old, with a population of close to 1.3 billion people over the age of 60.1 Ageing presents as a major risk factor for various chronic diseases such as Alzheimer’s disease, cardiovascular disease, cancer, diabetes, and hypertension. All these add to the pressure on healthcare systems to work towards developing healthcare services in order to meet the medical needs of older people. This gave rise to an alternative preventive approach of promoting healthy ageing, to reduce economic and social stress of a rapidly ageing population.
In the year 2016, the World Health Organization (WHO) came up with a framework, to call for a coordinated global strategy to help older people age healthily.2 The United Nations Population Fund (UNFPA) has also identified population ageing as a key mandate area, and will help governments develop community-based support for the elderly as well as promote specific policies.1
With global initiatives in place, research and development also has its part in promoting healthy ageing to further prepare communities for an ageing population.
What is healthy ageing?
According to the WHO guidelines, healthy ageing is the process of developing and maintaining the functional ability that enables wellbeing in older age.3 Functional ability is further broken down into intrinsic capacity and environmental characteristics.
- Intrinsic capacity
This constitutes the mental and physical abilities of an individual that is influenced by the occurrence of disease, injury, and age-related changes.
- Environmental characteristics
The environment refers to the community they live in, their homes, as well as other factors such as the built environment, societal values, healthcare facilities, and support services from the society.
While these are considered when discussing healthy ageing at a healthcare and policymaking standpoint, we can look at it further from age-related diseases at a molecular level. There have been many associations with age-related diseases and various biomarkers. Some of the prominent diseases include Alzheimer’s disease, Parkinson’s disease, cardiovascular disease, and cancer. By understanding the pathophysiological mechanisms of these biomarkers that lead to the manifestation of age-related disease, researchers can discover links that help promote healthy ageing and preventive care for the ageing population.
"It means maintaining high functionality and being disease-free even though you are getting chronologically older. At the molecular level, your body has built in networks to maintain homeostasis and even though you are ageing, you remain highly functional. However, when these networks become compromised, you lose homeostasis and that is when you are at high risk for a wide range of chronic diseases."
Dr Brian Kennedy
In a systematic analysis for the Global Burden of Disease Study 2016,4 the number of deaths within the Asia-Pacific region due to dementia is more than 260, 000 with a prevalence of more than 4.2 million. This translates into higher cost and disease burden on healthcare systems, with an estimated cost of US$185 billion. These numbers are expected to triple in the coming years with growing ageing populations.5 This highlights a major factor to focus on healthy brain ageing for the elderly in order to reduce these rising costs.
"Healthy brain ageing is the ability to maintain ‘normal’ cognitive performance and exhibit a lower rate of brain atrophy. Mild cognitive impairment and dementia are major neurodegenerative disorders that affect the elderly and younger people as well. Most neurodegenerative disorders cannot be reversed, or curable, and only symptomatic relief is available."
Dr Nady Braidy
Many studies have shown that neurodegenerative disease manifestation is related to several molecular processes. Some of which include oxidative stress, mitochondrial dysfunction, programmed cell death (apoptosis), telomere shortening, and inflammation. Identification of biomarkers for these processes will provide a measurable indicator of the pathology in neurodegenerative diseases.
Biomarkers associated with ageing and age-related disease
Some common biomarkers of ageing as proposed by Lara et. Al., include biomarkers of physiological functions (blood lipids, fasting glucose) to biomarkers of immune function (Interleukin – 6, Tumor Necrosis Factor (TNF) – alpha).6
Other biomarkers associated with age-related diseases include oxidative products in the blood, presence of extracellular amyloid plaques in Alzheimer’s disease, and nicotinamide adenine dinucleotide (NAD+) levels in the body.
A prominent biomarker in the healthy ageing scene is NAD+, which has been found to decline with age. In a recent clinical study, NAD+ plasma levels are reduced significantly across increasing age groups.7 With this association, enhancing NAD+ levels in the body provides therapeutic potential for age-related diseases as well as promotion of healthy ageing.
Does the secret to healthy ageing lie in NAD+ levels?
NAD+ is an essential cofactor for several biological process, especially in the production of cellular energy – Adenosine Triphosphate (ATP) – through the tricarboxylic acid cycle. It has three precursors, nicotinic acid (Na), nicotinamide (Nam), and nicotinamide riboside (NR). NAD+ is a crucial component in bioenergetic and signaling pathways making it a major regulator in cellular homeostasis. Many of these pathways contain NAD+ dependent enzymes, which have been found to mediate age-related diseases when NAD+ levels decline with age.
Research has shown that decline of NAD+ occurs during ageing, it is also linked to age-related diseases such as, Alzheimer’s disease, diabetes, and atherosclerosis. Thus, demonstrating the possibility of targeting NAD+ in promoting healthy ageing and prevention of age-related diseases.8
Studies on animal models has found that increasing NAD+ levels extends the lifespan, which further justifies the correlation of NAD+ with ageing.
Through this evidence, targeted therapies can be developed and applied in order to promote healthy ageing. In a randomized, double-blind, placebo-controlled clinical trial, long-term use of NAD+ precursor supplementation has been found to be well-tolerated and increases NAD+ levels in healthy middle-aged to older adults. This study also found that NAD+ supplementation poses potential benefits in reduction of blood pressure and arterial stiffness.9
"Several studies by my group and others have shown that increasing your body’s NAD+ levels may be a useful strategy to maintain a healthy redox status and improve functioning of the Central Nervous System (CNS) by increasing brain mitochondrial respiratory deficits, protecting against amyloid-beta – induced toxicity and cognitive impairment, and ameliorate reactive glial – induced motor neuron loss, and maintenance of neural stem and progenitor cells."
Dr Nady Braidy
Venturing further into the therapeutic potential of NAD+ supplementation, nicotiamide riboside (NR) chloride vitamin termed NIAGEN® has been recently shown to increase whole blood NAD+ in a dose response manner. The study conducted by researchers from ChromaDex Corp. showed no adverse effect from prolonged use of NIAGEN® over the clinical trial period.10
"There were two primary aims of the study. One was to do a large enough study to demonstrate the safety at different dosages to show that there were no side effects and that it was safe. The second major aim was to demonstrate the most important thing that NR raises NAD+ levels. Which we did achieve in this study through a dose response reaction."
Mr Frank L. Jaksch
From current research and development on NAD+ supplementation, there is hope for it as a potential therapeutic solution to promote healthy ageing and prevention of age-related diseases.
Maintaining a balance
Other than supplements, ensuring enough physical exercise and having a healthy diet is important for promoting healthy ageing. Proper nutrition can be supplemented with pharmaceuticals but having a balanced diet does also play apart.
"Exercise from an ageing population standpoint is critical, and as you age you will lose muscle mass. The goal would be to minimize the loss of muscle mass as you age and minimize disease and loss of function. This will increase the potential of how long you will live."
Mr Frank L. Jaksch
"Strategies aimed at promoting healthy brain ageing and slowing down cognitive decline are warranted. Numerous studies continue to show that nutrition plays a major role in maintaining a healthy brain and reducing risk factors associated with cognitive decline and reduced brain function.
Dr Nady Braidy
Taken collectively, the promotion of healthy ageing requires a multifactorial approach. These factors comprise of combined efforts by governments and global organizations in ensuring policies and initiatives are in place for the elderly to maintain their functional abilities and have an environment that meets their healthcare needs. Research and development of technology and healthcare products that provide a preventive edge to age-related diseases is also a contributing factor. Lastly, the mindset of the community and personal determination in ensuring a healthy lifestyle through physical exercise and proper nutrition will complete the healthy ageing bundle as populations prepare for a rapidly growing ageing population.
- Ageing, UNFPA, Retrieved from: https://asiapacific.unfpa.org/en/node/15208
- Global strategy and action plan on ageing and health, Retrieved from: https://www.who.int/ageing/GSAP-Summary-EN.pdf
- What is healthy ageing? Retrieved from: https://www.who.int/ageing/healthy-ageing/en/
- GBD 2016 Dementia Collaborators (2019). Global, regional, and national burden of Alzheimer's disease and other dementias, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet. Neurology, 18(1), 88–106. doi:10.1016/S1474-4422(18)30403-4
- Dementia in the Asia Pacific Region, Retrieved from: https://www.alz.co.uk/dementia-in-the-asia-pacific
- Lara, J., Cooper, R., Nissan, J., Ginty, A. T., Khaw, K. T., Deary, I. J., Lord JM, Kuh D, Mathers, J. C. (2015). A proposed panel of biomarkers of healthy ageing. BMC medicine, 13, 222. doi:10.1186/s12916-015-0470-9
- Clement, J., Wong, M., Poljak, A., Sachdev, P., & Braidy, N. (2019). The Plasma NAD+ Metabolome Is Dysregulated in "Normal" Aging. Rejuvenation research, 22(2), 121–130. doi:10.1089/rej.2018.2077
- Aman Y, Qiu Y., Tao J., Fang F. E. (2018). Therapeutic potential of boosting NAD+ in aging and age-related diseases. Translational Medicine of Aging, vol. 22, pp 30-37. https://doi.org/10.1016/j.tma.2018.08.003
- Martens, C. R., Denman, B. A., Mazzo, M. R., Armstrong, M. L., Reisdorph, N., McQueen, M. B., … Seals, D. R. (2018). Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nature communications, 9(1), 1286. doi:10.1038/s41467-018-03421-7
- Conze, D., Brenner, C., & Kruger, C. L. (2019). Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. Scientific reports, 9(1), 9772. doi:10.1038/s41598-019-46120-z
Frank L. Jaksch, ChromaDex Co-Founder & Executive Chairman
Mr. Jaksch holds a Bachelor of Science degree in Chemistry and Biology from Valparaiso University in Valparaiso, Indiana. He is a member of the American Chemistry Society, the American Herbal Products Association, the American Botanical Council and the NSF Joint Committee for Dietary Supplements, and the Natural Products Association (NPA).
Nady Braidy, Ph.D.
Dr Braidy has an ARC Discovery Early Career Research Fellowship and is currently Head of the Brain Ageing Research Laboratory at the Centre for Healthy Brain Ageing (CHeBA) at UNSW Sydney, Australia. He has been previously awarded the NHMRC Early Career Research Fellow (2013-2016) and was the sole recipient of the Alzheimer's Australia Viertel Foundation Postdoctoral Research Fellowship in 2012. He was one of 5 people to be awarded the Australian Academy of Science, Science and Industry Endowment Fund to represent Australia at the 64th Lindau Nobel Laureate Meeting. Dr Braidy has also been awarded the International Investigator of the Year Award in Geriatric Psychoneuro-pharmacology and received the UNSW Faculty of Medicine Dean's Rising Star Award for Excellence in Postdoctoral Research.
Brian Kennedy,, Ph.D.
Dr. Brian Kennedy is internationally recognized for his research in the basic biology of aging and as a visionary committed to translating research discoveries into new ways of delaying, detecting, and preventing human aging and associated diseases. He is a Professor in the Departments of Biochemistry and Physiology at National University Singapore and Director of the Centre for Healthy Ageing in the National University Health System. From 2010 to 2016 he was the President and CEO of the Buck Institute for Research on Aging. Currently he remains as a Professor at the Institute. Dr. Kennedy also has an adjunct appointment at the USC Davis School of Gerontology. Dr. Kennedy is also actively involved Biotechnology companies, serving in consulting and Board capacities, as well as Scientific Director of Affirmativ Health. Dr. Kennedy also serves as a Co-Editor-In-Chief at Aging Cell.