By Megan Lee
This article was originally published in The Oxford Scientist Michaelmas Term 2021 edition, Change.
A world in which immortality is possible may seem dystopian, although surging interest among billionaires into anti-aging research means a large portion of the biotechnology industry now aims to make this a reality. The newly founded Altos Labs joins a growing register of well-funded start-ups aiming to reverse aging. Is such extensive investment into this field justified, and who will ultimately benefit?
Age is the greatest risk factor for a host of devastating diseases, including Alzheimer’s disease, cancer, cardiovascular disease, and many more. Currently, researchers are exploring the biochemical mechanisms underpinning the hallmarks of aging, with the goal of developing therapeutics for aging-related diseases. Although there are some dietary supplements currently available associated with anti-aging effects, such as resveratrol, rapamycin, and metformin, there is no concrete evidence of their efficacy as therapeutics. A high-profiled previous foray into anti-aging research, Unity Biotechnology, involved a drug to treat osteoarthritis that failed at clinical trials, leading to a 60% drop in shares and a major restructuring of the company that saw the anti-aging research division axed.
Thus far, advances in cell reprogramming look far more promising than small-molecule drugs as anti-aging therapeutics. This reflects the productivity crisis in drug discovery, and a general trend towards biologics, which are drugs derived from natural sources. In 2006, Shinya Yamanaka identified what are now known as the Yamanaka factors: four proteins that reprogramme the developmental clock in cells, producing induced pluripotent stem cells (iPSCs) from adult cells. Pluripotent stem cells are capable of self-renewal and differentiation into any adult cell type, and are only present in the embryo, presenting significant ethical issues to any applications. The production of iPSCs showed that differentiation is reversible, and no genomic information is lost during development. For this remarkable discovery, Yamanaka and Sir John Gurdon were jointly awarded the 2012 Nobel Prize in Physiology or Medicine. The therapeutic potential of iPSCs has already been well demonstrated, with thousands of clinical trials currently being carried out with ex vivo (outside of the body) reprogrammed cells. For example, the NIH launched a clinical trial in 2019 to treat macular degeneration with iPSCs produced from patient blood cells and reprogrammed ex vivo to generate retinal pigment epithelial cells.
However, in order to reverse aging, cells need to be reprogrammed in vivo (within the body). This presents significant challenges, since somatic ageing must be reversed, but not development. For example, when reversing aging in a neuron, the goal is not to reprogram it back to a stem cell, but instead to rejuvenate it and remove the hallmarks of ageing. Moreover, in vivo reprogrammed cells have a tendency to lead to cancer development due to the integration of genes into the genome, premature termination of reprogramming and altered epigenetic regulation, among many other reasons. Hence, using Yamanaka factors to induce reprogramming in vivo is associated with high mortality in mice, caused by cancer. There are only a handful of published papers demonstrating the possibility of in vivo reprogramming, and it is widely understood that there are still significant hurdles facing translation to the clinic.
This begs the question of whether such extensive investment into cell reprogramming is justified, given how nascent it is. Hundreds of millions of dollars have been poured into anti-aging start-ups, funded by the likes of Larry Page, Peter Thiel, and Larry Ellison, all of which aim to use in vivo reprogramming to reverse aging. Moreover, it is important to distinguish between treating the diseases of aging and attempting to reverse aging itself, the latter of which creates a host of ethical problems. There is no question that the ‘cure’ for aging will be expensive – the rejuvenation industry is dominated by the private sector precisely because it requires large, risky investments into an extremely novel technology with very little translational evidence.
Although understanding the biochemical mechanisms underpinning aging and treating age-related diseases is important, the surge in research to reverse aging does not have the general populace’s interests at heart. As long as the current hyper-capitalist biotechnology industry persists, billionaires will drive scientific innovation to the benefit of the rich only, and to the detriment of the remainder of society.
