To go along with Nature Medicine's latest focus issue on aging and the prospects for producing therapies to treat aging, I see that Science Magazine's December 4th special issue covers much the same topic. It is interesting to see this example of a convergence of discussion in respected publications, representative of a greater willingness by the scientific community to earnestly consider and plan a path towards the medical control of aging.
I used the occasion of the Nature Medicine issue to complain about the present mainstream research focus; when it comes to aging, the majority of scientists involved in the field undertake research programs that cannot possible produce meaningful results in terms of additional years of healthy life. Meanwhile approaches that can in principle produce real, actual rejuvenation in old people, and prevent aging in the young, are neglected in comparison. Today I'll instead focus on the more positive side of things, which is that the treatment of aging is now a serious, accepted, legitimate field of research within the broader scientific community. It took twenty years of persuasion and slow bootstrapping of research results to get to this point, but now here we are.
Ten or fifteen years ago for scientists to talk in public about extending healthy human life spans was to risk funding and career, which certainly stunted the pace of progress. There has been a sea change in the last few years as the results of advocacy flourished - things couldn't be more different now. Within the extended research community the important arguments today are over how aging should be treated, not whether or not it is plausible, useful, or desirable. The common sense position has finally won out among scientists: aging should be treated because it is the cause of age-related disease, and it is a given that we should work towards curing and preventing age-related disease because it is a source of suffering, pain, and death. If you think that suffering, pain, and death are bad things, then you should be all for working as hard as possible to end degenerative aging. It is the greatest single cause of suffering, pain, and death in the world by a very broad margin: more than 100,000 lives lost every day, and hundreds of millions of others in various states of pain, frailty, and disability.
The dream of cheating death has evolved into a scientific quest to extend healthy life span. Scientists and doctors are looking for ways to maximize the number of years that we live free of chronic diseases, cancer, and cognitive decline. But before we can intervene, we have to understand the cellular and molecular mechanisms that drive aging and senescence. Some clues reside in our telomeres, the tips of our chromosomes that shrink with age. Others lie in our stem cells, which can only go on for so long repairing our tissues. Our mitochondria, too, the so-called powerhouses of the cell, may hold some answers to prolonging youthfulness. Other research points to changes in the gut microbiota associated with frailty in the aged. At a mechanistic level, the modulation of coenzyme NAD+ usage or production can prolong both health span and life span. Current geroscience initiatives aim to harness basic insights in aging research to promote general advances in healthy aging.
Questions remain throughout the aging field. By tweaking everything from genes to diets to environmental temperature and mating, scientists have created Methuselah flies and other remarkably long-lived animals while garnering fundamental insights into the biology of aging. Still, researchers puzzle over the most basic questions, such as what determines the life spans of animals. Meanwhile, a handful of molecular biologists are searching for ways to measure a person's biological, as opposed to chronological, age, but that quest, too, has proved elusive. An ever-growing literature addresses both theoretical and pragmatic approaches to the challenge of aging. In this special issue, we have focused mainly on the cellular aspects of mammalian aging, with the goal of spurring future developments in promoting health span, if not life span.
The longest lived laboratory animals shed light on the forces that lead some to any early grave and others to beat the odds and see many more birthdays than the norm. Experiments with mice, flies, and worms have won that manipulating genes, restricting calorie intake, and giving animals drugs can extend life span - by as much as 10-fold. Researchers also have elucidated several biochemical pathways that lead to longevity. And one lab animal, the hydra, appears to have found a fountain of youth of sorts: Unless it sexually reproduces, it appears immortal.
Research into stem cells and aging aims to understand how stem cells maintain tissue health, what mechanisms ultimately lead to decline in stem cell function with age, and how the regenerative capacity of somatic stem cells can be enhanced to promote healthy aging. Here, we explore the effects of aging on stem cells in different tissues. Recent research has focused on the ways that genetic mutations, epigenetic changes, and the extrinsic environmental milieu influence stem cell functionality over time. We describe each of these three factors, the ways in which they interact, and how these interactions decrease stem cell health over time. We are optimistic that a better understanding of these changes will uncover potential strategies to enhance stem cell function and increase tissue resiliency into old age.
Age is the greatest risk factor for nearly every major cause of mortality in developed nations. Despite this, most biomedical research focuses on individual disease processes without much consideration for the relationships between aging and disease. Recent discoveries in the field of geroscience, which aims to explain biological mechanisms of aging, have provided insights into molecular processes that underlie biological aging and, perhaps more importantly, potential interventions to delay aging and promote healthy longevity. Here we describe some of these advances, along with efforts to move geroscience from the bench to the clinic. We also propose that greater emphasis should be placed on research into basic aging processes, because interventions that slow aging will have a greater effect on quality of life compared with disease-specific approaches.