The University of Newcastle, Australia

Dr Doug Smith is investigating the impacts of ageing on the nervous system, with the aim of identifying interventions that will extend healthspan.

Lifespan encapsulates the number of years you are alive, whereas healthspan refers to the number of years you maintain mental and physical health, without serious disease, during your lifespan.

Dr Doug Smith wants you to live better for longer. That doesn't necessarily mean living for longer, although that may be a benefit of good health. He isn't interested in finding the elixir of youth, just the key to maximum healthspan. 

"Some people want to live forever, I have no interest in extending lifespan, I want to extend healthspan, it's a very different thing," he explains.

With life expectancy increasing and family sizes decreasing, our national population is ageing fast, prompting urgency in research in this field.

"In about 20 years from now, there are going to be more people living in Australia who are over the age of 65 then under the age of 15," Doug asserts.

"If more people reach their latter years still in pretty good shape, physically and mentally, then presumably we can lessen the health care cost burden."

"And more importantly, those people will have a better quality of life."

NERVOUS SYSTEMS

With a background in neurobiology, Doug is focusing his study on the impacts of ageing on the nervous system.

The central nervous system (CNS) includes the brain and spinal cord, whilst the peripheral nervous system (PNS) comprises all the body's nerve pathways outside of the CNS. Both the CNS and PNS are affected by ageing.

For example, declining senses, slowing of messages controlling movements, a loss of clarity in cognitive processes and failing memory are all nervous system specific changes that have been attributed to ageing.   

Using an animal model to study the ageing brain, spinal cord and vestibular (balance) system, Doug and his collaborators hope to further understand these changes on a cellular and molecular level.

Together with his team, Doug uses modern genomics approaches, such as next generation sequencing, to obtain a global picture of age-related gene expression changes to inform their directions in the lab.

"There is much more that we don't know than we do know, so doing a discovery driven approach first, that can then can direct us, is very powerful," he says.

Doug and his team then use more traditional hypothesis driven approaches when looking to confirm or refute possible truths suggested by the broader genomics data.

MICRODISSECTION

Utilising laser-capture microdissection (LCMD) technology, the team are able to identify and extract specific cell types from the highly complex nervous system for study.

For example, LCMD extraction allows the team to investigate the effects of ageing on dopamine neurons, the degeneration of which causes Parkinson's disease. They also investigate the breakdown of the blood brain barrier, which is seen in vascular dementia.

Another study saw the team comparing levels of mitochondrial DNA mutation in young and old tissue. Mitochondria are the power generators of a cell and they have their own very small genome. Age-related mutations in this genome are thought to compromise the ability of mitochondria to generate energy for the myriad of cell activities needed for proper nervous system function.

"Based on our genomics findings we are now doing a lipidomics investigation," Doug explains. 

"The CNS is chock full of different types of lipids, and we know they change with ageing, so we are trying to understand those changes in greater detail."

"Once we align these various approaches, it will give us a really good indication of where to head in terms of our more focused or directed studies."

THE NEXT GENERATION SEQUENCERS

Doug credits PhD and undergrad students with undertaking the bulk of the laborious lab work.

"We are always looking for more students who are passionate about biology and who would like to work with us," Doug says and adds, laughing, "Bring your own money!"

A senior lecturer in the School of Biomedical Sciences and Pharmacy, Doug admits that although teaching drains research time and energy, it actually enhances his outcomes.

"I actually believe that teaching is good for your research because when you teach you have to stand back and take a bigger picture view of things," he says.

"And when you do that, sometimes it gives you a different perspective for your research."

Doug was a post-doctoral scientist when a fascination with the biological phenomenon of ageing drew him to this field of study.

"I have always been curious, I have always wanted to know how things work," he conveys.

"Age related degeneration just doesn't make much sense. A lot of energy and effort goes into creating a sexually mature organism. So, why not then just maintain it? I find it very interesting."

AGEING GRACEFULLY

Although studies across species and domains show that ageing has a major impact on both the animal and human body, some individuals seem somewhat resilient to the effects of ageing.

"Everybody has a grandma or elderly uncle that still seems to be running around like a sprightly 30 or 40 year old, both mentally and physically they are doing really well," Doug acknowledges.

"We are trying to determine what it is about these individuals that allows them to have such a good healthspan."

"A potentially disappointing outcome of our work would be that we find out what the cause or causes of ageing are, but we can't find an intervention."

"However, there are many examples of people ageing well, and if you look at what they do, they are all pretty active, not just physically but mentally as well."

FREEDOM OF CHOICE

Due to the mounting evidence, Doug suggests it is more realistic to earn a longer healthspan, than win one in the unexplained resilience to ageing jackpot.

He refers to several existing intervention studies that show vastly different outcomes for participants relative to different diets and levels of exercise.

But don't wait too long. Evidence emerging from Doug's lab suggests the ageing process begins much earlier than we would like to believe.

"Preliminary data is certainly indicating that if you are going to live well, you can't wait until you are 75 and then decide to make healthier choices."

In the end, the solution to retarding the ageing process may simply involve choices around modifying behaviour.

"Once we characterise some of the processes of normal ageing, we can then go and see if a high fat, high sugar, Omega 3, or resveratrol diet, and/or exercise, are going to change the ageing process at the molecular, cellular, organ and whole body levels," Doug explains.

"The next step would be to design interventions that can be applied to human populations. Humans won't like some of the dietary restrictions, or the exercise. The red wine they might go for," he smiles.

"People will always have free will. We are just trying to figure out ways that are acceptable to the majority to help them to age well and stay active for longer."