Longevity Science: Time To Turn Back Time

Opinions expressed whether in general or in both on the performance of individual investments and in a wider economic context represent the views of the contributor at the time of preparation.

Executive Summary: The appeal of living a healthier and longer life is clear. It’s also becoming an increasing reality. Think of the human body as just another piece of hardware to be hacked, optimised and upgraded. Longevity science is a developing discipline that embraces genetics, biology, medicine and technology. It matters since an ageing population with growing chronic conditions raises the cost of health and social care. Advances in longevity science are helping to shift the healthcare paradigm from reaction to pre-emption, improving the capabilities of already healthy people. Multiple moonshots are underway. Many will fail and others will encounter practical, scientific and ethical issues. However, over $8bn of venture capital flowed into the sector in 2024. Businesses want even a small share of the $600bn longevity-focused healthcare market. Equity investors have multiple ways of playing this theme, which we expect only to grow in importance.

Your author is getting older. This phenomenon is unquestionable. In the six years since we last wrote on longevity science as a future trend, more grey hairs have appeared, as have several facial lines. Nonetheless, your author feels at least as healthy as he did back in 2019. This may just be luck, although lots of exercise and a good diet have probably helped.

Death is one of life’s very few certainties. Think of it as a common enemy, but one that unites humanity. To counter this, mankind has always looked for ways to boost its powers. This may be mentally – via education – or elsewhere. Consider basics such as clothing and glasses, or, more recently, wearables to monitor health. Ageing is one of the toughest biological problems to crack – but it won’t stop people trying.

Very few people live beyond 100. In America and Britain, centenarians currently make up around 0.03% of the population (per the United Nations, or UN). The reason: as time passes our bodies become worse at replacing faulty or mutated cells. This weakness allows damaged cells to build up, compromising healthy tissue and helping to accelerate disease process. Ageing is a key risk factor for the diseases common in high-income countries: cancer, heart disease and neuro-degenerative diseases such as Alzheimer’s and Parkinson’s.

The good news is that UN data show that the average life is likely to be ten years longer by the end of this century than currently, on a global basis. With technology and science, it is now possible to conceive more easily of living beyond 100, perhaps to 120 and beyond. The idea of genuine elixirs is now gaining credence. When polled, 74% of people say that they like the idea of living a long and healthy life beyond the age of 100 (according to VML Intelligence).

The caveat to this discussion is what’s the point in extending life if it’s going to be spent suffering in ill health? More remarkable is the idea not only of ageing, but of ageing healthily. Any debate about longevity needs to disintermediate lifespan with healthspan – for the two are different. Put another way better health can mean longer life. Whereas lifespan refers to the total number of years a person lives, healthspan is a concept that focuses on the number of those years that a person remains free of significant illness or disease.

The gap between lifespan and healthspan is growing. At the turn of the century, it was 8.5 years. Now it has risen to 9.6 years (per 2019 data – the last available – from the World Health Organisation, or WHO). For women, the gap is typically 2.4 years longer than for men. A more recent UK study conducted by the National Health Service shows that 20% of men’s lives and 23% of women’s are currently spent in poor health. Reframe the debate: most people agree that an improved healthspan is the priority.

The medical profession would describe longevity science as the ability to live a long life beyond the species-specific average age at death, practically, it is a multidisciplinary field that investigates the biological and physiological processes of ageing to potentially extend lifespan and improve healthspan. The burgeoning field of longevity science embraces genetics, biology, medicine, and technology. Some think of the human body as just another piece of hardware to be hacked, optimised and upgraded.

Crucially, the quest for longer, healthier lives is not merely a pursuit of individual aspiration but has broader societal implications. Advances in longevity science matter since an ageing population significantly increases the cost of health and social care. The pace of population ageing is now much faster than in the past. Between 2015 and 2050, the proportion of the world’s population over 60 years will nearly double from 12% to 22%, according to the WHO.

A higher prevalence of chronic conditions in this ageing population would not only increase healthcare and social costs but also have a clear impact on public finances. By way of example, a study in the British Medical Journal shows that US healthcare spend is forecast to grow at an average annual rate of 5.6% between 2027 and 2032, in contrast to a projected 4.1% p.a. rise in GDP over the same period. Add into this burden increased welfare spending and the pressures only rise.

Longevity science can help address these challenges through a range of mechanisms. The field is broad and nascent and would include at least the following five areas. These comprise understanding the biological mechanisms of ageing, identifying potential interventions, exploring the role of genetics and lifestyle, developing technologies for life extension and focusing on healthy longevity.

If there is an overarching principle, then it could be seen as changing the paradigm in healthcare. Think about longevity science as trying to shift emphasis away from treating debilitating afflictions towards improving the capabilities of people who are already healthy. Another way of viewing the discussion is to think about solutions being aimed at pre-emption rather than reaction. Longevity science can become the toolkit for allowing humans to live better.

Such a broad opportunity implies that there are multiple different (and sometimes overlapping) moonshots underway. Not all will be successful. However, as developments in adjacent fields overlap, they should become mutually reinforcing. Below follows a non-exhaustive list of some of the areas where research is underway.

Begin with medicine. Genomics and regenerative medicine are at the forefront of biotech solutions. The falling cost of decoding the genome has produced a swathe of genetic data, which can be augmented and optimised via the power of AI. Emerging solutions could involve CRISPR or mRNA. The former is a gene-editing technology that allows scientists to make precise changes to DNA.

CRISPR technology (which we first discussed in 2017) offers a promising avenue for improving longevity by addressing the root causes of cellular ageing and age-related diseases. By precisely targeting and editing genes, CRISPR can repair damaged cells, enhance cellular regeneration, and correct genetic defects associated with ageing. Meanwhile, think of mRNA as acting like a messenger, delivering the blueprint for a specific protein to the cellular machinery that builds it. Studies in organisms such as roundworm have shown that alterations in mRNA splicing and translation can extend lifespan.

Elsewhere, work is underway in fields such as personalised stem cells, regenerative medicine and senolytics. Think of stem cells as a repair system for the body. Personalised stem cells involve using a patient’s own stem cells to create tailored therapies or disease models. This approach allows for treatments that are specifically adapted to the individual patient’s unique genetic makeup, disease presentation, and cellular environment. 

An alternative approach involves using regenerative medicine as a mechanism for replacing, engineering or regenerating human cells, tissues, or organs to restore or establish more normal functions. Recent advancements in this space are making the prospect of ‘manufacturing’ human organs a reality.

In the field of senolytics, scientists are developing a class of drugs that selectively target and eliminate senescent cells. Senescent cells have permanently stopped replicating but continue to live and secrete molecules that can contribute to inflammation and tissue damage. Senolytics selectively target and eliminate senescent cells, potentially improving overall health and potentially slowing or reversing age-related declines. In preclinical studies, senolytics have shown promise in delaying, preventing, or alleviating frailty, cancers, and other age-related conditions. They have also been shown to improve physical function and increase lifespan in mice.

At the same time, significant work is underway in respect of lifestyle choices and solutions.  The links between health and diet have never been clearer. Data from the World Health Organisation show that almost 75% of all deaths globally occur owing to chronic diseases. Crucially, 80% of those deaths arose from cardiovascular disease, cancers, prolonged respiratory diseases and diabetes – all of which are impacted by unhealthy diets.

Against this background, significant work is underway in the overlapping fields of nutraceuticals, sirtuins, calorific restriction, peptide injections and ozone therapy. The first of these combines the terms ‘nutrition’ and ‘pharmaceutical’ and relate to products that can provide medicinal effects. Common examples include vitamins and minerals, omega-3 fatty acids, probiotics, and herbal extracts like turmeric or ginseng. Like many nutraceuticals, sirtuins are naturally occurring with sources of sirtuin-activating compounds including green tea, red wine, kale, and dark chocolate. These enzymes have been implicated in extending lifespan in yeast, worms, flies and mice by helping to regulate metabolic processes and DNA repair.

Other studies have shown that reducing calorie intake can extend lifespan in various organisms, though its effects in humans are still being investigated. Such an approach can slow metabolism and reduce oxidative stress. Another approach involves peptide injections to promote immunity and improve other functions such as gut repair. Think of peptides as short protein chains that deplete with age. One high-profile example is semaglutide – known to many as Ozempic or Wegovy – which has been shown to promote weight loss in some individuals. Some in the medical profession believe that GLP-1s (glucagon-like peptides – per the above) may replace diet and exercise as the first line of defence for preventing heart disease in the future.

Project further out and there may be a role for ozone therapy. The approach of administering ozone gas causes reactions that form more proteins and red blood cells, which in turn increases oxygen supply. It has been used in the treatment of infections and viruses. Other benefits may include improved circulation, lower inflammation, potentially higher energy levels and sharpened brain function.

Moonshots are also underway in respect of brain-computer interfaces (or BCIs). Think of these as mechanisms that pass signals directly between biological brains and semiconductor chips. Such interfaces could not only help restore movements after accidents but help in areas such as rehabilitation and cognitive function improvement. AI will likely play a major role in how quickly BCIs develop. More extreme longevity solutions could include widespread organ printing, cryonics (the practice or technique of deep-freezing the bodies of people who have just died, in the hope that scientific advances may allow them to be revived in the future) and even mind-uploading (where humans exist in perpetuity in a metaverse).

The only problem with all the above is that advocates naturally radiate optimism. The history of longevity science contains multiple defunct ideas. Innovators (and investors) need to battle against multiple scientific, ethical and practical concerns. Begin with the most basic: it may be both naïve and hubristic to assume that we can defeat death. Something will kill you eventually. Natural selection has no interest in longevity per se. An individual is simply a means to make copies of itself, as opposed to being an end in itself.

Even with advances, we still don’t fully understand how or why the body ages. Extensive research, testing and regulation is therefore required before many proposed solutions can hit the market. Not all drug-approval agencies recognise old age as a treatable condition, making trials harder to register. Further, by their very nature, trials must follow thousands of people over many years, adding to their cost and complexity. One solution may be multiple small-scale trials running in parallel. However, these may encounter the additional challenges relating to cost (and eventually reimbursement). Do not forget the Trump administration’s current plans to restrict university funding.

Advocates may also run into challenges relating to population growth and resource allocation. How might we share scarce resources such as food, water and energy (not to mention housing) among an ever-growing population? Then there is the debate about inter-generational equity and the impact of longer life in one cohort at the expense of the younger population. Consider too whether a world that grows older would become trapped in stasis, lacking the fresh ideas of the young that characterise progress.

Fear of the unknown is not uncommon and Malthusian concerns about over-population have not come to pass thus far. Short-term scepticism needs to be balanced against medium-term open-mindedness. Scientists have, of course, hacked our biology successfully in the past. Whereas test-tube babies were once seen as not only impossible but also unnatural, assisted reproduction is now readily accepted. Over 10m IVF babies have now been born globally. Small gains in extended healthspan can make a difference – especially for those who care.

Venture capital investment into the longevity sector has continued to grow, reaching $8.5bn in 2024. This was more than double 2023’s figure ($3.8bn) according to lifespan.io, a data provider. Over 300 deals occurred in the space last year. Although the sector has often been a posterchild for manias and overshoots, the available opportunity is significant. Even a small slice of the longevity-focused healthcare market would be meaningful. Consultants (such as Oliver Wyman) value the broad market at $600bn today and estimate it could be worth over $1tr by 2050.

Many start-ups have evocative names such as Blueprint, New Limit, Rejuvenation Technologies and Shift Bioscience. Several tech billionaires are involved in the space. Perhaps, if you already have everything, then you may be keen to try and ‘buy’ eternal youth. Altos Labs, a biotechnology company focused on cellular rejuvenation, secured a recent $3bn valuation in a Series D funding round backed by Jeff Bezos. Elon Musk is involved actively in the space (via Neuralink, his BCI project) as are the founders of Google via various projects.

From a listed equity perspective, there are multiple ways of gaining exposure to the theme. These could include investing in biotechnology and therapeutics, healthcare diagnostics, healthcare services and tech infrastructure. Other approaches may involve focusing on wellness and lifestyle or beauty industry businesses such as Galderma that are involved in developing anti-ageing solutions. Companies involved in the development of life science tools may be other beneficiaries. An ageing population may also mean the need for more seniors housing and medical premises. Several ETFs such as AGNG and IDNA also exist. Watch this space as the theme looks set only to run from here. We’re not getting any younger any time soon.

The above does not constitute investment advice and is the sole opinion of the author at the time of publication.Past performance is no guide to future performance and the value of investments and income from them can fall as well as rise.

Alexander Gunz, September 2024