Telocyte Newsletter, Q3 2024: Three Unicorns

The painting above depicts a family of three unicorns, a detail easily overlooked if one fixates on the intricate brushstrokes rather than stepping back to appreciate the entire picture. Discovering three unicorns in a painting, or achieving breakthroughs in age-related disease treatments, hinges on identifying the right targets amidst a sea of complexities. A narrow focus on background details is a common stumbling block, and rarely leads to solutions. Too narrow a focus often obscures broader and more fundamental understandings, understandings which may lead to revolutionary insights and fundamental advances in medicine.

Many large national hospital systems are enamored of targeting outcome measures of clinical efficiency, hoping to increase the quality of clinical care while lowering the costs of that same care. A naive view would assess these as perfectly reasonable targets. Yet the use of naïvely identified targets can result in unforeseen – or even disastrous – outcomes. For instance, one hospital aimed to shorten patient stays to boost efficiency, a goal all too easily achieved by simply discharging every patient even as they register. This would enormously reduce the length-of-stay, but it ignores overall quality of care. Healthcare systems must balance efficiency, cost-effectiveness, and safety within the overarching objective of providing compassionate and high-quality patient care. Similarly, biomarkers of aging, while informative, only gain significance when viewed within the intricate web of aging processes as a whole. Biomarkers of aging can be invaluable, giving tangible and clear information about the aging process, but the naive use of biomarkers must not be confused with the understanding the overall process nor assumed to provide insight into effective points of intervention.

Too often, biomarkers are seen as independent clinical targets. The reality is that biomarkers have value only in the broad context of the complex cascade of aging as a whole. The aging process as a unified, dynamic system and not merely a collection of independent parts. To ascribe aging to mitochondrial dysfunction begs the question of why the mitochondrial dysfunction occurs in the first place. To think that all aging diseases are secondary to immune system aging begs the question of why the immune system ages at all. DNA damage, autophagy, protein changes, beta amyloid deposits, tau tangles, and hundreds of other biomarkers are targeted by academic and pharmaceutical firms the world over, but none of these biomarkers are aging, nor do they shed enough light on the underlying causes of age-related diseases. Targeting clinical biomarkers is no more useful than targeting a single naïve measure of hospital care. To intervene in aging – or in age-related diseases – requires fundamental intervention in the system not in its biomarkers, no matter how comprehensive the list of biomarkers we choose.

Failing that, we fail clinical care, we fail our patients, and we fail ourselves.