Targeting multimorbidity: Using healthspan and lifespan to identify biomarkers of ageing that pinpoint shared disease mechanisms

Abstract

Advancing age is the major risk factor for chronic diseases, such as cardiovascular disease, type 2 diabetes, cancer and Alzheimer's disease. The rising number of older individuals is thus resulting in an increased burden on our healthcare system. Instead of tackling each of these age-related diseases one by one, focused approaches aimed at the identification of shared disease mechanisms, that can ideally be targeted using lifestyle and/or pharmacological interventions, could be more productive. But, how do we identify the vulnerable people in the population that are at high risk for developing (multi) morbidity? This is a question that the research community tries to answer by looking for so-called biomarkers of ageing, i.e. markers that are predictive of age-related morbidity and mortality. When they are successfully identified, such markers can be used as surrogate endpoints in clinical trials or intervention studies that are aimed at improving general health.According to the criteria of the American Federation for Aging Research (AFAR) a perfect biomarker of ageing should; (a) outperform chronological age in predicting age-related disease and mortality, (b) be simple (i.e. accurate and reproducible) and inexpensive to test without harming the test subject, and (c) work in both humans and model organisms to make findings directly translatable [1]. Several potential biomarkers of ageing have been proposed [2], including clinical markers involved in physiological (e.g. fasting blood glucose, glycated haemoglobin, and blood lipids) and immune function (e.g. C-reactive protein), but, thus far, none has met all the proposed AFAR criteria.Many of the proposed biomarkers have shown to be associated with the risk of specific age-related diseases, e.g. an imbalance in fasting glucose or blood lipids has been associated with the onset and progression of type 2 diabetes or cardiovascular disease, respectively. However, it is still unclear if these biomarkers are able to predict

A proteomic signature of healthspan

“…They defined healthspan as the number of years from birth to the first occurrence of conditions in our healthspan definition plus hip fracture. Additionally, a critique of both definitions is that, except for dementia, late-onset diseases are underrepresented, meaning those who remain disease-free may not necessarily be in good health 35 . Including additional late-onset diseases is unlikely to significantly change our results, as the UKB is a relatively young cohort, and our goal was to train a predictor for early interventions.…”

Multimorbidität im Versorgungsalltag – Definitionen, Strategien und Grenzen

“…Deswegen ist es wichtig, zwischen "Healthspan" zu unterscheiden, also den Lebensjahren ohne chronische Erkrankungen und den damit verbundenen Einschränkungen, und "Lifespan", der generellen Lebenserwartung. Die Healthspan ist in den letzten Jahrzehnten nicht im gleichen Maße wie die Lifespan angestiegen, sodass der Mensch zwar länger, jedoch mit multiplen chronischen Erkrankungen lebt [3].…”

Identifying Metabolomic and Proteomic Biomarkers for Age-Related Morbidity in a Population-Based Cohort - the Cooperative Health Research in South Tyrol (CHRIS) study

“…In turn, these health outcomes feed back into the underlying biological processes impacting the rate of aging and enhancing the risk for further disease 4 . It is therefore important to enhance our understanding of the molecular basis of age-related diseases to improve measures for disease prevention and general health 5 . Omics-based biomarkers provide insights into the molecular processes driving functional decline, they also help monitoring health trajectories, age-related physiological decline and disease onset 6 .…”

“…Omics-based biomarkers provide insights into the molecular processes driving functional decline, they also help monitoring health trajectories, age-related physiological decline and disease onset 6 . Such biomarkers can also support the development of prevention strategies targeting those processes and provide surrogate endpoints in intervention studies 5 . The goal is early identification of individuals at higher risk of diseases, who will benefit most from such preventive interventions 7 .…”