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Metabesity 2022

Session Highlights

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 


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 


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  


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 


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 


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  

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 


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  


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 


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 


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 


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  


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 


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 


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 


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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