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Healthy Aging: Antioxidants, Adaptogens & Cognition

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Healthy Aging: Antioxidants, Adaptogens & Cognition Healthy Aging: Antioxidants, Adaptogens & Cognition Karen Butler Michael Altman, CN, RH (AHG) Kieron Edwards, Ph.D. Senior Editor Herbalist Nutritionist Chief Scientific Officer Informa Markets Anthocyanins International LLC Sibelius Natural Products (SeattleCancerCareAlternatives.com) David Heber, M.D., Ph.D., FACP, FASN Katie Stage, N.D., RH (AHG) Professor Emeritus and Founding Director, Therapeutics Division Director UCLA Center for Associate Professor, Southwest Human Nutrition College of Naturopathic Medicine (SCNM) Booth #5310 Towards healthy aging Kieron Edwards PhD MBA www.sibeliusnaturalproducts.com OCTOBER 2019 1 Talk outline Booth #5310 . The trends and challenges of aging . What occurs during aging? . Theories, effects, and pathways of aging . Supporting healthy aging 2 Aging: The monster at the end of the Booth #5310 book 3 The trends and challenges of aging Booth #5310 4 What is aging? Booth #5310 . Ageing results from the impact of the accumulation of a wide variety of molecular and cellular damage over time. This leads to a gradual decrease in physical and mental capacity, a growing risk of disease, and ultimately, death. But these changes are neither linear nor consistent, and they are only loosely associated with a person’s age in years (WHO) 5 Age-related changes to health Booth #5310 . Physical aging . Sensory loss, body composition changes, osteoarthritis . Cognitive aging . Immune aging . Immunosenecence, inflammation . Cardiovascular health . CVD is still the leading cause of death in older adults . Metabolic health . Cancer . Second leading cause of death in older adults 6 Living longer and better? Booth #5310 . Human lifespan is increasing . Almost 2 years increase per decade . Age is a major risk-factor in many human diseases and conditions . 62% of Americans over 65 have more than one chronic condition (Ward et al., 2013) . Healthspan has not increased at the same rate (Bellantuono et al., 2018) 7 An aging global population Booth #5310 . Global population over 60 years . 1980 – 382 million . 2017 – 962 million (over 80 137 million) . 2050 – 2.1 billion (over 80 425 million) . Growth much faster in less developed countries . But still occurring in developed countries 8 (Statistics from “World population ageing; 2017 highlights” report, United Nations) An aging global population Booth #5310 . Larger number of older adults but also increasing percentage . By 2050 35% of European and 28% of N. American populations will be over 60 (United Nations, 2017) . Projections in US have older adults (>65) outnumbering children (<18) by 2035 . Great burdens on individuals and society . Provision of social- and health-care 9 Aging: A challenge and an opportunity Booth #5310 . Higher percentage of older adults take supplements . Healthy aging supplements sales are growing . Is the opportunity bigger? . Not just Baby Boomers . Millenials taking greater interest . Awareness from caring for older relatives . Concern for cognitive and physical decline . Realisation of importance of lifestyle choices 10 What occurs during aging? Booth #5310 (Lopez-Otin et al., “The Hallmarks of Aging”, Cell 2013 11 Programmed, error, or both? Booth #5310 . Pre-programmed process . Regulated by the neuronal, endocrine system, and changes in gene expression over time . Natural selection will act on longevity if it is beneficial to fitness . Accumulation of damage or errors over time . Cumulative damage form intrinsic and extrinsic factors cause the reduction in function of biological system 12 Mitochondrial dysfunction and ROS Booth #5310 . Mitochondrial function declines with age . Reduced ATP production . Increased leakage from electron transport chain – increased ROS and damage to biomolecules (DNA, proteins, lipids...) . Free-radical theory of aging . Gradual accumulation of damage by ROS leads to cellular aging • Superoxide dismutase (SOD) proteins present in all aerobic organisms • However, hormetic effects of ROS as well and ROS important to cell signalling 13 (Image credit: Stroo et al., Frontiers in Neuroscience, 2017) Build up of un-degradable molecules Booth #5310 . Multiple mechanism lead to build up of molecules . Toxic by-products of normal metabolism e.g. Lipofuscin “age-pigment” . Mis-processed or mis-folded of proteins e.g. Amyloid proteins . Advanced glycation end products (AGEs) . Contributes to breakdown of intracellular processing and transport mechanisms . e.g. autophagy and proteolysis . Intracellular and extracellular aggregates . Tau aggregates or Amyloidβ plaques . Atherosclerotic plaques 14 (Image credit: Stroo et al., Frontiers in Neuroscience, 2017) Senescence Booth #5310 . Stable arrest of the cell cycle SASP . Linked to telomere shortening, DNA damage, Inflammation mitogenic signals... Senescent cells accumulate in aged tissues . SASP: pro-inflammatory conditions may contribute to aging . Inflammation a major risk factor in many age- related diseases . Contributes to decline in stem cell populations with age . Reduced regenerative capacity . Atrophy and immunosenecence • e.g. thymus 15 (Image credit: Stroo et al., Frontiers in Neuroscience, 2017) Core pathways of aging Booth #5310 . Studies in model organisms have identified several key pathways of aging conserved across species . Insulin IGF-1 Signalling (IIS) pathway strongly conserved . Together with its core targets FOXO and mTOR . Principally related to glucose sensing . Mediates DR/CR benefits . Decreased IIS results in lower rates of cell growth and metabolism and therefore lower rates of cellular damage 16 Core pathways of aging Booth #5310 . Inter-connected aging network . Nutrient sensing plays a core role . IIS – Glucose . mTOR – amino acid concentrations . AMPK – low energy status [AMP] . Sirtuins – low energy status [NAD+] . Regulates balance of anabolism and catabolism . Pro-longevity treatments mimic low nutrient availability . e.g. Rapamycin (Barzila et al., Perspectives in Diabetes, 2012) 17 Supporting healthy aging Booth #5310 18 Healthy aging Booth #5310 . There is undeniably a strong role of accumulation of error and damage over time in aging . Some of these factors are intrinsic, but other drivers are external . e.g. Environmental damage and stresses . Can we slow down or even reverse this damage? . Slow down the sand-timer 19 Clues from other species Booth #5310 . What positive interventions to take? . Calorie restriction has demonstrated increased longevity across multiple species . First demonstrated in rodents in the 1930s . Various treatments also show consistent effects across multiple species . Rapamycin, Resveratrol, Curcumin... Act on these core pathways of aging 20 Clues from long-lived humans Booth #5310 . Role for genetics in longevity, but it is still a plastic trait . Long-lived people in “Blue-zones” show some consistent behaviours Sardinia, Italy Ikaria, Greece . Diet • Moderate calorie intake/intermittent fasting • Rich in plant-based foods Loma Linda, CA • Moderate alcohol . Physical activity Nicoya, Costa Rica . Sleep . Mood Okinawa, Japan • Social interaction, sense of purpose, avoidance of chronic stress... 21 Supporting healthy aging Booth #5310 . Positive lifestyle interventions have the potential to increase longevity and delay the onset of age-related pathologies . Supplements can make a key contribution to this • Mimic calorie-restriction without the down-sides . Demonstrating benefits in humans poses a challenge . Aging is not recognised as a disease . How do you measure aging? . To date limited evidence of efficacy in humans beyond epidemiological studies 22 Summary Booth #5310 . Aging poses a significant challenge to individuals and society . Basic research has identified many of the hallmarks associated with aging . Slowing down the accumulation of age-related damage has promise to delay the on-set of age-related pathologies . Improve peoples healthspan . Lifestyle interventions, including supplements, have the potential to contribute to this 23 Going beyond slowing down? Booth #5310 . Lifestyle interventions may slow down – or even reverse – some forms of age-related damage . Other elements will likely require medical interventions . e.g. Senence, tissue atrophy, accumulation of AGEs lipofuscin etc. Relevant technologies are being developed so it is conceivable that these could be tackled as well . Gene and enzyme therapies, stem-cell therapies, immunotherapies 24 Booth #5310 25 Booth #5310 A Nutraceutical Platform Technology for Health THANK YOU Sibelius [email protected] Kieron Edwards PhD MBA www.sibeliusnaturalproducts.com 26 NEW RESEARCH WITH ANTIOXIDANT INGREDIENTS David Heber, MD, PhD, FACP, FASN Professor Emeritus of Medicine and Public Health Founding Director, UCLA Center for Human Nutrition DISCLOSURES McCormick Science Institute – Honoraria and Travel Herbalife Nutrition Institute – Honoraria and Travel POM Wonderful – Research Awards Inflammaging Information Classification: General How Do You Measure Age? • Chronological age does not correlate perfectly with functional age, i.e. two people may be of the same age, but differ in their mental and physical capacities. • Each nation, government and non- government organization has different ways of classifying age. • Divisions are sometimes made between the young old (65–74), the middle old (75–84) and the oldest old (85+). Information Classification: General Dunedin Study A longitudinal investigation of health and behavior in a complete birth cohort. Study members (N=1,037) were all born between April 1972 and March 1973 in
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