Commentary on Gaps in the Knowledge of Aging
There are any number of sizable gaps in the understanding of how aging progresses at the detail level, which processes are more or less important, the direct of causation for many different interactions, and so forth. Aging is very complex because a living organism is very complex. Even simply causes produce complex outcomes when operating in a complex system. The same sizable gaps in understanding exist when we ask how and why aging evolved to be near universal across the tree of life, given that physical immortality appears possible for lower animals, and for much the same reasons. The evolutionary landscape is a complicated environment.
The scientific impulse is to make progress towards full understanding of a system as it exists, but one can argue that finding answers to these questions will not actually be all that helpful when it comes to the near future production of the first generation of rejuvenation therapies. Those therapies must necessary address forms of molecular damage and disarray that cause degenerative aging, and which are already identified and well enough understood to allow meaningful progress towards interventions. Comprehensive lists of starting points and modes of therapy to be developed have existed for years, such as the Strategies for Engineered Negligible Senescence. The research community is nowhere near as ignorant of the causes of aging as it is of how exactly aging progresses in detail, and the human impulse is to change systems that are not ideal, such as the present state of degenerative aging, as soon as the tools exist to do so.
Today's open access paper is more reflective of the scientific impulse than the human impulse. It results from a narrow survey of researchers in the field, requesting commentary on unanswered important questions relating to aging. Thus we see a focus on the evolution of aging and why aging progresses differently between species and between individuals of the same species. This results from the urge to obtain a complete understanding, which remains somewhat distinct from what might be done effectively and soon to improve the state of aging. In fact, the state of research and development is one in which more might be learned, and more rapidly, by deploying the first rejuvenation therapies and observing the results, than by a more hands-off continued investigation of mechanisms without meaningful intervention.
Seven knowledge gaps in modern biogerontology
About a year ago, members of the editorial board of Biogerontology were requested to respond to a query by the editor-in-chief of the journal as to what one question within their field of ageing research still needs to be asked and answered. During the following couple of months, a majority of the editorial board members responded with their precise, and sometimes not-so-precise, questions, ideas and opinions. Based on those responses, this editorial article is my attempt to identify and compile a list of knowledge gaps in the biology of ageing research, and these are arranged under three main and general categories: (1) evolutionary aspects of longevity; (2) biological survival and death aspects; and (3) heterogeneity in ageing progression and phenotype. The implications of these knowledge gaps in biogerontology, especially in the context of ageing interventions for human health and longevity, are also discussed.
1. What are the evolved public (universal) and private (species-specific) longevity assurance genes for the essential lifespan of a species?
2. What is the nature of imperfections that limit the optimal functionality of the longevity assurance processes, and are they sex-specific?
3. With almost identical physical-time scales at the level of metabolic processes, how is the passage of biological-time regulated from one biological stage to the next through the life-cycle and until death?
4. What are the quantitative and qualitative features of the homeodynamic space in terms of the health and survival ability of a biological system?
5. What determines heterogeneity in the rate and extent of age-related changes at various levels of biological organization, from molecules to the whole body and population levels?
6. How to distinguish between harmful, useful, and neutral changes occurring during ageing?
7. How to identify and quantify the ability to tolerate, adapt, compensate and bypass age-related changes?
Since ageing is primarily a progressive loss of health, the focus of interventional strategies requires a shift from the treatment and prevention of diseases to the maintenance, recovery and enhancement of health. Such trends can already be seen emerging and being adopted.