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Metabesity 2022

Session Highlights

1 

Keynote Lecture: Breakthroughs at the Tipping Point: The future of health, medicine, aging and longevity?  

  • what we need to do to match lifespan to healthspan 

  • how recent scientific breakthrough on COVID-19 revolutionized speed in scientific research that is now needed to be applied to aging research  

  • healthy longevity is the new frontier: definition of old is no longer 65 

  • the problems with long-term healthcare costs and why current medical insurances are not adequate to handle the increasing aging population 

  • US spends more for healthcare and has the worst life expectancy than most other countries: need for drastic changes in the US healthcare system  

  • politicians should target the aging population and multiply funds for research on aging  

  • the need to leverage the expertise of older people and make them active and useful members of our societies 

  • the need to target healthy longevity for all, not just billionaires 

2

Selected Scientific Topics in Aging: Longitudinal phenotypic markers of aging and other multidimensional prognostic approaches for age-related chronic diseases 

  • the three different metrics of aging: biological aging, phenotypic aging, and functional aging 

  • what the global longitudinal phenotypic score is and how it differs from other measures of aging 

  • the need for identification of biomarkers that can predict longitudinal phenotypic decline, so that interventions targeting the reduction on the rate of aging are developed 

  • the epigenetic age clock is a better predictor of cognitive decline compared to chronological age  

  • a newly identified 76-protein proteomic clock that can better predict chronological age 

3

Selected Scientific Topics in Aging: Mitochondria dysregulation and the integrated stress response in inflammaging and cellular senescence

  • how mitochondria, the integrated stress response and inflammation relate to aging  

  • that impaired mitochondrial function is associated with the aging clock and the progressive course of chronic diseases 

  • the key role of mitochondrial bioenergetics in regulating our epigenome  

  • the ongoing battle between COVID-19 downregulating mitochondrial genes and the host upregulating the uninhibited genes 

  • the effects of caloric restriction: what's maximally beneficial for growth and fertility is not beneficial for longevity  

  • how the integrated stress response pathway boosts longevity pathways  

  • how treating mitochondrial dysfunction can guide novel treatments for long COVID-19  

4

Achieving Evidence to Support Healthy Longevity Therapeutics & Products  

  • what are Healthspan products? 

  • how can we obtain substantial scientific and clinical evidence for a regulatory approval? 

  • the need for the Congress and the FDA to recognize aging as a disease  

  • can FDA shift from approving one product for one disease to approving one (or more) product for multiple chronic diseases? 

  • what are clinically meaningful endpoints for assessing aging and which surrogate markers or biomarkers should be used? 

  • how can we leverage knowledge obtained from AI-assisted analyses of multi-omics data for the identification of new biomarkers and changing the design of clinical trials? 

  • how deficiencies of the current regulatory framework on foods and supplements can help the design of a new regulatory system for Healthspan products 

5

Identification and Adoption of Novel Biomarkers and Endpoints for Healthy Longevity Initiatives 

  • the latest updates on the Framework for Identification of Operational Outcomes in Geroscience (FROG) research initiative: a multidisciplinary workforce for the study of aging and age-related chronic diseases 

  • how can novel biomarkers of aging be identified and how they relate to sensitive to interventions and clinically meaningful endpoints 

  • how to measure health and resilience  

  • the value of the generation of multi-dimensional biomarkers/surrogates associated with not only to one but multiple chronic diseases  

  • aging-related multi-morbidity is a disease of inequity where the strongest predictor is our zip code.  

  • geroscience-guided therapies will benefit individuals with the greatest burden of chronic diseases, for whom poverty and inequity are a major issue 

6

What Should be the Elements for a National Policy on Healthy Longevity? 

  • lessons that the US can learn pertinent to international policies on aging  

  • the immense societal and economic growth that will arise by investing in older people  

  • how a national policy for healthy longevity can protect vulnerable people from future pandemics 

  • the benefits of implementing courses on healthy longevity into colleges and even schools  

  • about the UK policy targeting five extra years of healthy life expectancy while minimizing health and inequalities  

  • about Singapore investing in older people as valuable resources with representatives and ministers from more than 12 ministries  

  • about Chinese insurance companies implementing programs pertinent to healthy longevity  

1 

The COVID-19 Pandemic as of Year 3: the Birth of a New Chronic Disease 

  • why health systems worldwide were not prepared to deal with the COVID-19 pandemic 

  • pandemics, including COVID-19, go through cycles of panic and neglect 

  • how international mistrust, miscommunication and lack of cooperation affected the COVID-19 response 

  • how countries should invest in preparedness and response for the next pandemics 

  • cooperation between scientists and policy makers is essential when informing the public  

  • how should inequities and disparities in health status and access be addressed  

  • the need to invest on meaningful sustainable action with a portfolio of medical countermeasures to prepare for the next pandemic 

  • what is the social cost that we are prepared to bear to deal with the next pandemic 

2

The Importance of Research Collaborations in Confronting Medical Crisis: The Covid-19 Example

  • about the emergence of a new chronic disease: long COVID-19 and its health and societal impacts 

  • about the Massachusetts Consortium on Pathogen Readiness (Mass CPR), initiated during COVID-19, aiming to address infectious diseases, chronic diseases and mental health issues 

  • how the COVID-19 pandemic boosted international scientific collaboration and communication 

  • new breakthroughs in understanding of pediatric COVID-19  

  • how can studying the chronic fatigue syndrome help address the long term sequalae of long COVID 

  • that long COVID is a disease of middle-aged people, currently affecting 2% of the US population. 

  • how pre-print publications have revolutionized scientific progress and speed of communication 

  • about the importance of research collaboration, sharing information and increasing the speed of communication for the combat of future epidemics  

3

Leveraging Novel Immunological Signatures and Biological Pathways to Reverse Immunosenscence and Inflammaging

  • aged individuals exhibit a poor antiviral immune response, slower viral clearance and resolution of systemic inflammation and enhanced post-infection disability 

  • defective T cell responses underlie impaired anti-viral immunity and decreased muscle function in aged hosts 

  • systemic chronic inflammation underlies the pathogenesis of aging and most non-communicable diseases and infectious diseases  

  • how can boosting the resilience of the aging immune system help deal with the COVID-19 pandemic and future pandemics  

  • senolytics can restore anti-viral immunity and vaccine effectiveness  

  • immune aging drives senescence in non-lymphoid tissues and reduces the ability of the immune system to clear existing senescent cells 

  • Cationic Amphiphilic Drugs, including anti-depressants and heart medications, share similar properties with pathogens and can act as senolytics 

  • the Inflammatory Age biological clock can predict frailty and multi-morbidity 

  • the use of spaceflight as a model to understand the process of accelerated aging and its effects on immune aging 

4

Targeting Root Causes of Neurodegeneration for Age-Related Chronic Diseases

  • about a common mechanism underlying the pathogenesis of multiple neurodegenerative diseases that involves deleterious interactions between brain-resident microglia and astrocytes  

  • how DNA damage in neurons drives the activation of microglia which generate neurotoxic astrocytes that secrete inflammatory mediators and kill neuronal cells 

  • that amyloids may not be the cause but the effect in neurodegenerative diseases 

  • senescence is increased in response to DNA damage and clearance of senescent cells reverses aging and features of Parkinson's disease and Tauopathies  

  • how amyloids protect against disease pathogenesis in multiple sclerosis through exerting immunosuppressive effects in the brain and the periphery 

  • how activation of the TNF-a receptor II in immune cells is therapeutic in Alzheimer's models  

  • clinical trials in the field are hard to design, take a lot of time and there is inconsistent clinical benefit even when there is unambiguous target engagement 

  • that early phase clinical research in neurodegeneration is of seminal importance to move the asset along to later stages of development  

  • future therapeutic strategies should simultaneously target the peripheral immune system and the DNA damage response and cellular senescence in the brain 

5

American Federation for Aging Research (AFAR) Update on SuperAgers and FAST (biomarkers) Initiative

  • that centenarians spend a very little time suffering from diseases 

  • that healthy longevity has strong genetic associations 

  • genes that inhibit growth hormone pathways enhance healthy longevity genes  

  • healthy longevity genes inhibit functions of genes associated with chronic diseases 

  • how the SuperAger Initiative, funded by AFAR, aims to identify healthy longevity genes in 10,000 centenarians  

  • about the FAST (finding aging biomarkers by searching existing trials) initiative that will utilize multi-omics data from clinical trials to identify aging biomarkers  

  • the need to determine biomarkers and surrogate markers that respond to gerotherapeutics and target multiple chronic diseases 

1

AI, Big Data and Devices for Healthy Longevity 

  • big data collected longitudinally can discover underlying health issues pre-symptomatically 

  • that the use of AI, wearables and devices can detect diseases outside the clinic reducing doctors’ appointments and hospital visits  

  • how wearables can predict health outcome and alert individuals prior to disease development 

  • about a new AI-generated tool that can predict glucose several hours into the future without the need of a CGM  

  • how severe stress increases biological aging that can be restored after alleviation of the stressor 

  • novel biological clocks that distinguish biomarkers that cause aging from those that respond to aging 

  • how to delay and eradicate lifestyle diseases through AI-assisted smarter eating and activity measurements 

  • how AI-guided mining of the host and microbiota transcriptome can aid preventive healthcare  

2

Scientific Editors discuss advances and challenges in targeting underlying common roots of chronic diseases and enhancing health span 

  • the need for journal editors to highlight and encourage studies focusing on preventing rather than treating disease  

  • preventive and biomarker studies need large and broad populations in terms of sex, ethnicity and age, and are costly and time-consuming 

  • aging studies should be performed in old mice that incorporate their tissue microenvironment, nutritional and behavioral aspects  

  • big data explosion through omics studies imposes a big challenge on how to analyze and review it 

  • about the lack of adequate training on biostatistics for analysis of multi-omics studies 

  • about the problem with the reproducibility of AI studies  

  • that scientists should be skeptical about pre-print publications as they lack the quality control provided by the peer-review process 

  • that journals need to implement mechanisms to ensure published studies are correctly promoted and disseminated to ‘lay’ editors and the public 

3

Commercialization: Who, What, How? 

  • the need to develop a novel healthy longevity commercial model that targets prevention of chronic diseases and intervenes early in the aging process 

  • Big pharma (Pfizer, Lilly and Novo Nordisk) is investing on agents that target type II diabetes and obesity but also show effects on multiple chronic diseases 

  • the 5-year ‘Cosmos’ clinical trial, funded by MARS, that included 21,000 participants and discovered protective effects of a cocoa supplement on cardiovascular outcomes, morbidity and mortality 

  • Cambrian Biopharma’s ‘steppingstone’ indication model where an aging target is identified and explored initially in a cardiac, metabolic, CNS indication, and then the same or a backup molecule is investigated in longevity studies 

  • the need to break the silos imposed by the current regulatory framework and enhance the communication and collaboration between big pharma and big food companies  

  • which are the biomarkers of health and how can they be used to help people monitor/manage their health or disease trajectories 

  • for most chronic diseases, the criteria for regulatory approval are not the same as the criteria for reimbursement  

  • need to establish an ecosystem involving biotech, pharma, food, and supplement companies to marshal healthy longevity science into clinical data and take it through regulators 

  • need to develop predictive biomarkers that inform on how the drugs are preventing the progression of chronic diseases 

4

Endogenous and Exogenous Ketosis in Health & Disease 

  • breakthrough scientific studies that have reshaped our thinking about ketones from toxic byproducts to cellular fuels  

  • similarities and differences between exogenous ketones and the ketogenic diet 

  • novel effects of ketones on regulating cellular metabolism, epigenetics, the gut and brain axis and inflammation 

  • the key role of ketogenic diets in reversing type 2 diabetes and lowering the risk of cardiometabolic complications 

  • how caloric restriction and fasting -generated ketones can decelerate aging  

  • the protective effects of exogenous ketones on head injuries during military training  

  • how the ketogenic diet can boost the efficacy of anti-cancer therapies 

5

Preempting Age-Related Chronic Diseases and Disabilities: How Do We Get There, Sooner than Later 

  • how to employ new, repurposed and/or combinations of agents as candidates for healthy longevity products  

  • what are the current advances on healthy-longevity candidate drugs, such as, metformin, rapamycin and rapalogs 

  • which are the biomarkers and clinical endpoints that reflect health instead of disease 

  • how can multi-omics data gathering, AI and biobanking be leveraged for the design of new anti-aging drugs and reshape the format of clinical trials 

  • about the MARS-funded, largest to-date food supplement clinical trial (‘COSMOS’) that discovered protective effects of cocoa flavonols on cardiovascular events, morbidity, and mortality 

  • what are the regulatory hurdles in conducting clinical trials with nutritional supplements  

  • how drugs targeting aging can help decrease health disparities and the life expectancy gaps among underserved populations 

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