Academia and industry seem to be focusing on projects that may not significantly extend human life span by treating aging as a medical condition. Many pharmacological approaches, such as calorie restriction mimetics and autophagy upregulation, have shown limited success compared to exercise. However, the Strategies for Engineered Negligible Senescence (SENS) viewpoint, which focuses on repairing cell and tissue damage, shows promise. The longevity industry is growing, with companies like Calico and Altos Labs investing billions in research. While the geroscience approach may not be perfect, it is the wrong direction to dismiss the entire longevity industry.
Inflated expectations: the strange craze for translational research on aging
The emergence of Hevolution and the XPRIZE Healthspan is just the latest development in a remarkable phenomenon: a dramatic upsurge in activity in the private sector aimed at developing treatments for aging, fuelled by a heady optimism that the time is nigh. Other examples that involve massive funding to achieve practical outcomes in applied research on aging include the California Life Company (Calico), into which some US$2.5B has been invested; and Altos Labs, which in 2022 raised US$3B from investors.
Here we ask the question: what is the basis for this optimism? The last quarter of a century has seen a concerted effort by scientists to understand the fundamental biological mechanisms of aging, and much ground has been covered. How has this informed the recent upswell in commercial activity? We suggest that the latter is an anomaly arising in part from developments within the aging research field a decade ago that were, in some ways, counterproductive. These include the emergence of the so-called geroscience research agenda.
What seems to have happened is the following. Advances in research on the biology of aging that culminated in the 1990s yielded startling implications. It seemed possible not only to understand the fundamental mechanisms of aging, but also to slow them down. These promising prospects led to the aging field becoming bigger and better, thanks to increased funding and the influx of many good scientists. As a result, standards of research grew more rigorous, including critical reassessments of earlier findings. Such careful research over the past two decades has, regrettably, undermined a number of the reasons for earlier optimism. Disappointingly, caloric restriction in rhesus monkeys proved not to have the same remarkable effects as those seen in rodents. Growth hormone defects that extend lifespan in mice were found not to do so in humans.
With the dwindling likelihood that humans possess the plasticity in aging seen in shorter-lived animals, and the failure of existing theories of aging, how should one further pursue research? Here two possible approaches may be envisaged. On the one hand, scientists could renew their efforts to develop an effective theoretical framework with the capacity to explain diverse phenomena of aging. On the other hand, research could focus on translating existing theoretical claims and experimental observations into therapeutic trials – preclinical or clinical. The pursuit of this strategy in the early 2010s marked the emergence of the geroscience agenda.
In the past, this strategy of prioritizing translational research in the absence of a good understanding of the basic science has sometimes proved successful, aided by brute force and serendipity. There are, however, also numerous instances where such trial-and-error approaches failed, sometimes involving investment of billions of dollars. The reader may pick their own examples. Unquestionably, for translational research to yield useful, practical applications, at least some level of scientific understanding is required. At issue is judging when the time is ripe to move from basic to translational research, particularly where large investments of money and effort are involved. The oddest thing about the translational geroscience approach is its combination of pessimism about understanding aging, and optimism about translational research. Arguably, the inverse is more realistic.
