Читать книгу Pathy's Principles and Practice of Geriatric Medicine - Группа авторов - Страница 49

Facing the global challenges of ageing,⁷⁵ scientists who study this phenomenon have realised there is great urgency to consolidate a body of knowledge that will be helpful in clinical care. The field of geroscience thus emerged,¹⁶ followed by perspectives about ‘creating the next generation of translational geroscientists’.⁷⁶ The geroscience hypothesis is the following: the accumulation of diseases and loss of functions with ageing is driven by common biological mechanisms. Understanding these mechanisms would allow measuring ‘biological age’, predicting adverse outcomes in late life, and ultimately identifying interventions that extend healthspan.

Efforts have been made to identify putative markers of biological ageing^27,46,77 but are hampered by (among other things) the lack of a consensual definition of what a biomarker of ageing should measure/predict. Death is obviously a significant outcome but can be preceded by a long period of multimorbidity and disability, so time‐to‐death per se is not a sufficient outcome for a biomarker of healthy ageing. Age‐related multimorbidity is considered because a single disease‐centred approach may focus research on a specific organ or on one limited physiological system. Frailty, conceptually defined as an age‐associated decrease in physiologic reserve, increasing vulnerability to stressors, can be considered a clinical metric of biological ageing.⁷⁸ There is also growing interest in measuring intrinsic capacity – a composite of all of an individual's physical and mental capacities⁷⁹ – as a key determinant of functional ability. Markers of biological age described in this chapter are linked to one or several of these outcomes, the multiplicity of which somewhat clouds this area of research. Defining a consensual, relevant set of outcomes should be a first significant step for geroscience.

Therapeutic opportunities targeting components of biological ageing (senolytics, inflammasome inhibitors, mesenchymal stem cells, calorie restriction mimetics, autophagy inducers, and so on) are promising. Besides pharmacological approaches, lifestyle interventions (e.g. with regard to physical activity and diet) are known to have beneficial effects on several biological components of ageing.^62,80,81 A better understanding of the biology of ageing would also probably revolutionise geriatric medicine by describing patterns of multimorbidity according to common mechanisms of multiple diseases in the same patient, paving the way to tailored interventions. Currently, geriatricians face overwhelming complexity and cascades of adverse outcomes requiring a broad knowledge of physiology and medicine and the ability to choose which symptom and/or disease (on a potentially long list) can be controlled with a positive effect on quality of life.²⁷

Thus a significant current need is to find biological explanations for the heterogeneity of phenotypical ageing, not only from the perspective of age‐related diseases or lifespan but also from a functional perspective. This is probably one of the biggest current challenges for science and medicine, but there is reason to hope that such an approach will help us promote healthy ageing and achieve optimal longevity for as many people as possible.