MoPAct Policy Brief: 5 Biogerontology: a novel tool to stay healthy in old age

Policy priority Healthy lifestyle interventions in particular regarding nutrition and vaccination need to be implemented early in life with a lifecourse perspective.

Summary: Key findings: • Accumulating evidence from experimental studies shows that aging is not inevitably linked with the development of chronic diseases. • Only 20-25% of healthy life expectancy (HLE) is predetermined by genes; lifestyle and environment play a major role. • Age-associated accumulation of molecular and cellular damage can be prevented or greatly delayed by lifestyle interventions e.g. dietary manipulations. • Classical strategies (e.g. nutrition, exercise, vaccination) require broad communication to public. • Novel strategies (e.g. dietary interventions, novel drugs, stem cells) need successful translation from the understanding of molecular mechanism to animal models to clinic. • To be successful interventions need to be started early Figure 1. Strategies to increase HLE. (1) Classical interventions include nutrition, exercise, vaccination, no smoking/alcohol/drugs. (2) Novel interventions include in life with a life-course perspective. dietary interventions, clearance of senescent and damaged cells, mitohormetics, stem cells, drugs against inflammation, rejuvenation factors from blood, telomeres, Background: epigenetic drugs, chaperons and proteolytic systems (novel interventions adapted from López-Otín et al., Cell 2013). Population aging is progressing fast in all developed countries. Aging is associated with the development of multiple serious chronic illnesses, including type 2 diabetes, hypertension, heart Prevention disease, stroke, cancer, cognitive impairment and increased Prevention prior to the development of age-associated diseases morbidity and mortality from infectious diseases. As people is key for successful aging. Vaccination is a well-established are living longer they are increasingly living with one or more strategy to prevent infectious diseases that account for one comorbidities - long-term health conditions that cannot be third of mortality in elderly above 65 years and are a major factor cured, but can be controlled by medication or other in the development of morbidity and disability. The efficacy of treatment - placing current health and social care systems the immune system deteriorates with age including its defence under unprecedented demand. mechanisms and vaccination success. In addition, there exist biological and socio-economic inequalities in infectious disease susceptibility that contribute to differences in healthy life years and life expectancy between men and women and across EU member states. Empirical studies show that there is a clear bias in susceptibility Translation to infectious diseases based on sex and gender. In line with Based on the important discoveries of biological mechanisms that also responses to some vaccines differ between men and in the aging process and possible intervention strategies, one women.To comply with sex-specific differences in immunity, crucial question is how to implement these new developments. composition and dosage of vaccines need to be adjusted What are the translational barriers? Which stakeholders need specifically for men and women in order to increase efficacy to be involved? How to communicate new treatments, diets, and reduce adverse reactions. devices etc.? How to convince end-users to use novel products? Not only vaccinations in the elderly are required to protect them In order to explore these questions we have used telehealthcare from disease, but a life-course perspective on vaccination with devices as a translational showcase. regular booster immunizations throughout adulthood is needed Numerous telehealthcare devices exist from basic personal to sustain protection till old age. Vaccine policies are not alarms and fall detectors through to complex monitoring devices consistent across EU member states and often specific for health-related vital signs. Such devices could be used to help recommendations for adult vaccination are missing. The lack individuals live at home for longer; however they often go unused of harmonization of vaccine recommendations and financial in practice. compensation programs across Europe leads to significant Our study suggested that few telehealthcare devices were differences in vaccination rates and consequently protected developed based on the principles of user-centered design. As individuals. In addition the public needs to be better educated a result many were non-intuitive, with the majority of the focus on the risks and benefits of vaccination to increase compliance group participants not recognizing the purpose of the devices with vaccination guidelines. These issues need to be addressed from their appearance alone. Expert interviewees argued that to provide more equal opportunities for healthy aging. this lack of user-centered design resulted in unused products and products that failed to successfully meet end-user needs. Intervention Public and professional awareness campaigns are required The great majority of age-related chronic diseases can be with appropriate funding mechanisms for users to gain access prevented, or delayed, with the implementation of healthy to devices. The numerous barriers require systematically nutrition, physical exercise and cognitive training interventions. addressing, so device usage is promoted enabling individuals Based on current data dietary manipulations are the most to live at home successfully for longer. promising interventions to increase HLE. Data from animal and human studies indicate that long-term calorie restriction Approach and methods: combined with an adequate intake of the required nutrients We have been running reviews of the current literature, induces multiple metabolic adaptations that decrease the risk of discussions with experts and internet-based research to developing type 2 diabetes, hypertension, cardiovascular disease identify the most important achievements in the field of and cancer. Recent discoveries indicate that meal timing is also biogerontology suitable for translation. We have summarized critical: both intermittent fasting as well as a food intake adjusted the findings on the most promising approaches in the field of to the diurnal rhythm impact on metabolic health and multiple nutrition and immunology in peer-reviewed publications. biological functions, even in the absence of modifications in overall calorie intake. Also the diet composition e.g. lowered In order to define barriers in the translation of novel biogeron- intake of proteins or specific amino acids influences health and tological findings and the uptake of novel technologies we have longevity in animal models. In addition, nutritional modulation conducted focus groups and expert interviews using telehealth- of the gut microbiome seems to affect metabolic pathways that care devices as model system. control cardiovascular health, cancer risk and inflammatory/ immune function. More studies are warranted to understand the intricate interactions of factors that regulate aging and age-associated chronic disease.

WP personnel (in alphabetical order): Beatrix Grubeck-Loebenstein Richard ASPINALL, Anglia Ruskin University, Cambridge, UK Head, Institute for Biomedical Aging (previously at Cranfield University, Cranfield, UK), Research Natasha CAMPLING (Cranfield University, Cranfield, UK University of Innsbruck, Austria PM6-24), Luigi FONTANA, Università degli Studi di Brescia, Brescia, Italy (previously at Università degli Studi di Salerno, Email: Beatrix.Grubeck-Loebenstein@ Salerno, Italy), Carmen GIEFING-KRÖLL, University of Inns- uibk.ac.at bruck, Innsbruck, Austria, Beatrix GRUBECK-LOEBENSTEIN, University of Innsbruck, Innsbruck, Austria, Günter LEPPERDINGER, Paris-Lodron Universität Salzburg, Salzburg, Austria (previously at University of Innsbruck).

This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 320333 Call Identifer: FP7-SSH-2012-1/No. 320333