Cracking the ageing code

Emerging technological advancements are driving innovations all around us, transforming how we live, work and interact with one another, today and in the future.

Over the past 20 years, scientists have acquired a much fuller understanding of the biological pathways of ageing and are developing ways to slow, stall and possibly even reverse its impact on the body and mind. RBC Wealth Management’s Head of Investment Strategy, Frédérique Carrier dives into a few of the most promising advances and explores the link between scientific breakthroughs and intriguing investments.

From lifespan to healthspan

Life expectancy has doubled over the past 150 years thanks to medical and social progress. Today, children born in high-income nations can expect to have an even chance of living past their 80s.

A lot of attention has now turned to extending healthspan, or the number of healthy years before the end of life. Between 16 percent and 20 percent of life is spent in a state of daily battle against an increasing burden of chronic diseases in late life, according to a 2018 article in Nature, a peer-reviewed scientific publication.

With populations ageing, health-care costs are surging and will likely continue to rise, putting a strain on society and the economy. The global population of people 60 years and older will reach 2.1 billion by 2050, according to the World Health Organisation. No country will experience this more acutely than China, which is expected to have more than 500 million people over the age of 60 around mid-century.

What is ageing?

Scientists have come up with two hypotheses to explain the cause of ageing from a biological point of view. Some contend ageing is caused by the same developmental processes that are useful early on in life, only that they continue to run haphazardly into adulthood, causing the deterioration that comes with old age. For instance, the bone loss that women experience after menopause could be the continuation of the processes that draw calcium from the skeleton to produce milk in breastfeeding mothers, or far-sightedness in middle age could be caused by the lenses of the eye continuing to grow into adulthood.

Others posit that ageing is the gradual loss of the body’s ability to repair itself. When it is young, the body repairs damage to ensure genes can be passed on to the next generation.

While scientists still debate the processes that drive ageing, they tend to agree on the physiological details of ageing, i.e., the cellular changes which accompany the progressive decline in physical functions over time.

In “Hallmarks of ageing: An expanding universe,” Carlos López-Otín, professor of biochemistry and molecular biology at the University of Oviedo in Spain, led a team that produced a widely used list of the characteristics of ageing in 2013. In 2023, they updated it to account for the advancements in biological sciences since initial publication. Twelve “hallmarks” were identified that worsen with age, accelerate if stimulated, and seem to slow down with treatment.

In a nutshell, some ageing mechanisms include:

• Genetic mutations accumulating
• Chromosome ends crumbling
• Tissue being blocked with debris
• Stem cells no longer dividing and becoming unable to create new cells
• Mitochondria, the powerhouses of cells, falling into disrepair
• Gut microbiome becoming less healthy

Most promise

In his book Why We Die: The New Science of Ageing and the Quest for Immortality, Venki Ramakrishnan, a molecular biologist and co-winner of the 2009 Nobel Prize in Chemistry, highlights three approaches which he judges as most promising:

1) Senolytics

This class of drugs is designed to target senescent cells – those that have ceased dividing. Non-cancerous cells reproduce themselves 40–60 times, after which cell division stops. The cells do not die but rather enter a zombie-like state called senescence. A young body clears out these decrepit cells by either triggering a self-destruction process or by using the immune system to kill them off. But both of these natural clearing-out processes become less efficient with age.

Senescent cells which accumulate in the body secrete inflammatory molecules, dripping destructive compounds into nearby tissue and inhibiting the proper functioning of healthy cells in close proximity. Science suggests that senescent cells are at the root of many ageing-related diseases.

2) Stem cell regeneration and cellular reprogramming

Another approach focuses on rejuvenating or reprogramming the cells, capitalising on recent developments in stem cell science. Stem cells are the reserves from which new cells can be produced to regenerate tissue and are already widely used in regenerative medicine. Many scientists are searching for applications in the hope of countering ageing. Researchers are seeking to reprogram cells so as to try to revert them to an earlier stage capable of regeneration.

3) Telomerase reactivation

Telomeres are segments of DNA at the end of each chromosome. Every time a cell copies its chromosomes and divides, telomeres become slightly shorter. When telomeres get too short or wear out completely, cells may stop dividing and become senescent.

Scientists are focusing on reactivating telomeres, to prevent them from shortening as cells divide. An enzyme, telomerase, has been discovered that can lengthen telomeres. This enzyme is usually only active in cells, such as stem cells, that divide a very large number of times, unlike normal cells. As the body deactivates telomerase as part of ageing, scientists are exploring whether it can be reactivated.

Good things come to those who wait

While Ramakrishnan is optimistic about these cutting-edge methods of combating ageing, it could take at least a couple of decades to create the necessary and successful therapeutics, in his view.

In the meantime, RBC Capital Markets, LLC Senior Biotechnology Research Analyst Luca Issi points out that healthspan can be materially expanded via better diagnostics, earlier intervention and improved therapies for diseases such as cancer and heart disease.

He notes that biotech innovations beyond ageing have flourished, enabling more efficient treatment of several conditions. For instance, multiple drugs have been approved in genetic medicine, which targets the genes behind a disease and manipulates them to make an impact for patients. So far, approvals have mostly been given to treatments for rare diseases such as spinal muscular atrophy and beta-thalassemia, an inherited blood disorder. But as the technology advances, approvals for treatments of more common illnesses, such as cancer, cardiovascular disease, or eye disease, are around the corner.

A good investment?

Investing in the “combating ageing” theme can be implemented via the biotech industry. Still, Issi points out that the most exciting biotech innovations may not necessarily translate into the most promising investments. Those companies that can successfully prioritise diseases with a meaningful unmet need and potentially large patient population, and execute on well-designed clinical trials are more likely to emerge as winners, in Issi’s assessment.

He believes investors should also evaluate the competitive landscape and the legal and regulatory environment to determine if a franchise is likely to remain viable. Assessing other secular changes and disruptive forces, such as technologies that could transform the value of both existing and emerging biotech franchises, is also key.

So close, yet so far

With scientists having clearer insight into the biological pathways of ageing, the prospects for positive healthspan outcomes appear more promising than 20 years ago thanks to a proliferation of effort including hundreds of companies exploring dozens of different compounds, and human clinical trials that are underway. Medical breakthroughs are possible, as the recent drugs targeting obesity – a condition which eluded treatment for decades – have demonstrated.

In the meantime, a good diet, exercise, and sound sleep seem to be the best strategy for those aspiring for a long and healthy life.