The Dublin Longevity Declaration
Aubrey de Grey and Brian Kennedy are prominent scientists in the longevity community who take very different approaches to the problem of human aging. They recently collaborated to write the Dublin Longevity Declaration, now posted online and signed by some of the leading figures in the aging research field, as well as fellow travelers in the longevity industry, founders of biotech companies attempting to implement interventions to treat aging. We live in a world in which the opportunity to produce actual, real, working rejuvenation therapies exists, but too few people believe this to be true. There is too little funding devoted to this goal. Declarations signed by prominent scientists, patient advocates, and biotechnology industry executives are one part of a broad range of advocacy that is still needed if we are to live in a world in which the treatment of aging stands alongside the treatment of cancer as a broadly supported goal.
For most of our history, even getting to old age was a significant accomplishment - and while centenarians have been around at least since the time of the Greeks, aging was never of major interest to medicine. That has changed. Longevity medicine has entered the mainstream. First, evidence accumulated that lifestyle modifications prevent chronic diseases of aging and extend healthspan, the healthy and highly functional period of life. More recently, longevity research has made great progress - aging has been found to be malleable and hundreds of interventional strategies have been identified that extend lifespan and healthspan in animal models. Human clinical studies are underway, and already early results suggest that the biological age of an individual is modifiable.
A concerted effort has been made in the longevity field to institutionalize the word "healthspan". Why healthspan (how long we stay healthy) and not its side-effect of lifespan (how long we live)? The reasons are linked more to perception than reality. Fundamental to this need to highlight healthspan is the idea that individuals get when they are asked if they want to live longer. Many imagine their parents or grandparents at the end of their lives when they often have major health issues and low quality of life. Then they conclude that they would not choose to live longer in that condition. This is counter to longevity research findings, which show that it is possible to intervene in late middle life and extend both healthspan and lifespan simultaneously. Emphasizing healthspan also reduces concerns of some individuals about whether it is ethical to live longer.
A drawback of this strategy exists, though: many current longevity interventions may extend healthspan more than lifespan. Lifestyle interventions such as exercise probably fit this mold. Many interventions that have dramatic health-extending effects in invertebrate models have more modest effects in mice, and there is a concern that they will be further reduced in humans. In other words, the drugs and small molecules that we are excited about today may, despite their hefty development costs and lengthy approval processes, only extend average healthspan by five or ten years and may not extend maximum lifespan at all.
Most experts in the field now acknowledge that this is a likely outcome in the near future and one focus of longevity medicine is now on achieving it. But far more is possible. Arguably, the avoidance of an emphasis on lifespan is a consequence of an overly pragmatic approach to two fundamental questions: Why do humans age and what can we do about it? These are surely two of the biggest questions in human biology. Although we try our best to ignore it, the prospect of an inevitable decline in health leading to mortality shapes our thoughts and actions. Despite the incredible advances in longevity research, these questions remain unanswered. What biological processes bring about the aged state? Can aging not just be significantly slowed, but more and more thoroughly reversed? How would humans, and their societies, be different if we achieve these goals?
It will cost billions of dollars in research and significant time to answer such questions, but we assert that it would undoubtedly pay for itself many times over. What cards need to be turned over to answer the longevity question? What interventional strategies are likely to take us beyond modest healthspan effects, and toward radical change in the rate of biological aging? Most of the lifestyle or small-molecule interventions that are currently being tested target pathways affecting longevity. These include those designed to improve metabolism, restore youthful immune function, maintain youthful body composition, eliminate deleterious cells, or improve cellular stress responses. But there are strategies on (and just over) the horizon that may have much bigger impact. These need to be seriously interrogated and resources need to be devoted to these big questions. There needs to be an acceptance and tolerance of significantly higher levels of failure in longevity research, knowing that big ideas are sometimes wrong and that the ones that are right will far outweigh the setbacks. Is radical lifespan extension foreseeable? No one can answer that question with certainty. But there are certainly enough tantalizing clues suggesting that aging is sufficiently malleable to warrant the allocation of very substantial resources.