Fight Aging!

The concept of a neatly packaged definition of a disease works well when dealing with the realm of infectious conditions. There is a pathogen, the pathogen causes certain symptoms, and one works towards intervention based on, for example, getting rid of the pathogen or interfering in its ability to do harm. Since medicine was largely concerned with tackling infectious disease until comparatively recently, the disease model has become very ingrained in the medical and regulatory community.

Unfortunately, this model doesn't work well for age-related disease. The situation is completely different. Aging involves a network of interacting, layered, underlying processes of molecular damage and consequent tissue dysfunction. Senescent cells and cross-links and calcification contribute to arterial stiffening, which causes hypertension, which harms the kidneys and the brain, joining the other forms of harm to the kidneys and the brain, and at some point in time the symptoms in any given organ cross over the line in the sand from "not a disease" to "we'll call this a disease". But calling it a disease really doesn't help to clarify what should be done about it.

That the disease model, formed in the era of the dominance of infectious disease in medical concerns, hasn't been helpful when it comes to guiding researchers towards the best strategies to treat age-related conditions is illustrated by the very slow progress made to date, across a lifetime of radical advances in all of the underlying technologies, such as materials science and computing, that enable the development of greater capabilities in medicine and life science research.

A different approach is needed for aging and its consequences, which is to largely abandon the idea of treating a specific disease, identified by a specific cluster of symptoms, and instead focus on treating a specific mechanism of aging. Identify a form of damage, such as the accumulation of senescent cells, and repair it, such as by selectively destroying those cells. Then assess the outcome.

The plasticity of ageing and the rediscovery of ground-state prevention

Disease is considered the most fundamental unit of analysis in medicine. The definition of disease is the object of ongoing philosophical debate between naturalistic, constructivist, and instrumentalist accounts. While there is no consensus on the concept of disease, the notion of disease is central to medicine. Until recently, the function of disease as the focus of medicine has gone unchallenged, due to its intuitive appeal as an obviously plausible target of medical intervention. However, the complexity of most age-related ailments, the fact that elders are affected by concomitant conditions (multimorbidity), and the fact that a great number of age-related symptomatic states escape clear nosological determination, have led some to question the utility of disease as the central focus of medical care.

In a provoking 2004 paper on the "end of the disease era," the authors explicitly criticized disease-centric medicine. They instead propose a more individualized approach that revolves around the clinical trade-offs necessary to manage a complexity of concomitant affections. Instead of treating each disease individually, medicine should strive to treat an individual patient's unique combination of diseases, and the way they affect physical and psychological functioning, as well as daily activities, goals, and life plans. The focus is less on discrete pathologies and survival, than on the reality of how an individual organism becomes diseased and weakened over time.

This post-disease paradigm is an example of a very general explanatory framework: one that considers multimorbidity, as opposed to discrete pathological states, to be the central focus of geriatric medicine. In this account, the health of the ageing person is best understood as the result of multiple concomitant pathologies.

In contrast, understanding health as the absence of disease is not compatible with the idea of measuring and protecting functional trajectories as the focus of geriatric care. From an epistemological point of view, this vision clearly resonates with the explanatory framework of ageing as a plastic phenotype. For researchers working on intrinsic capacity, the disease construct is inadequate for capturing how an individual fares in her environment in functional terms. Function, not disease, is the object of care in this clinical perspective on ageing.

The same applies to the molecular version of the explanatory framework. Researchers in this domain are not interested in linking alterations in metabolic pathways to the manifestation of a given discrete pathology. Their focus is rather on the role of those pathways in maintaining organ functionality over time. This, in turn, can translate into the delayed onset and slowing down of multiple diseases of old age. The longitudinal focus of intrinsic capacity emphasizes prevention over reaction even in the absence of a specific clinical phenotype.