1 The Prospects that Emerging Science Offers Us forLong Healthy Lifespans October 7, 2014 Great Presenter Series Wayland Public Library PART 1 Vince Giuliano
2 TOPICS PART 1 Overview on the sciences of aging PART 2 Actions and interventions for extending healthspan and lifespans – Focus on the personal and practical
3 THE SCIENCE OF AGING (selected views)
4 State of science – The relevant scientific literature is vastUnderstanding aging takes us into just about every area of human biology and medicine Image source Almost every body system, subsystem, molecular pathway and gene regulation program varies with aging More than a million new publications every year Growth in PubMed.org publications Now around 21.5 million indexed research publications
5 THE RESEARCH PARADIGM IS CHANGINGState of the science THE RESEARCH PARADIGM IS CHANGING THERE IS ALSO AN EXPLOSION IN THE VELOCITY OF BIOMEDICAL RESEARCH COMMUNICATIONS THERE IS ALSO AN EXPLOSION IN THE VELOCITY OF BIOMEDICAL RESEARCH COMMUNICATIONS
6 “While physics is infinitely deep,”State of the science “While physics is infinitely deep,” “biology is infinitely complex” I want to avoid the above two presentation pitfalls What I have to say here is simple but lends itself to extreme depth of complexity. A more-complete version of the story is in the handout and online versions of the presentation
7 Differentially expressed enzymes in Purine MetabolismImage source
8 Brain tumor pathways
9 Metabolic pathways
10 Composite network of molecular pathways active in HCV-infected liver tissue.
11 State of the science Purine metabolism – image source Image source There are thousands of such diagrams to be found in the literature not all consistent, mostly unconnected with other related diagrams The research tends to be solid but extremely complex. Because of this, researchers in one field usually can’t and don’t follow the literature in possibly-related fields.
12 It is rarely studied that wayLIMITS OF THE CURRENT CULTURE OF RESEARH Aging is multilayered The aging of a living organism is both a manifestation and a result of complex changes in composition, structure and function across all levels of biological organization from molecular pathways, cell components and cells, to organs and tissues, to whole-body systems. Almost all research investigations have been carried out at a specific single level of organization and often in isolation with a relatively narrow focus. It is rarely studied that way
13 Research is reductionistic and highly focusedThe dominant methodology and culture that dominates biological and biomedical research across the entire spectrum of research activities internationally. This traditional strategy has unquestionably led to significant progress and remarkable insights
14 Research is reductionistic and highly focusedThe dominant methodology and culture that dominates biological and biomedical research across the entire spectrum of research activities internationally. This traditional strategy has unquestionably led to significant progress and remarkable insights if we are ever to have a fully developed, fundamental understanding of aging and longevity and their relationship to health A more integrated approach is needed
15 So, how does science speak with regard to aging?With many tongues Important findings about aging can come from cancer research, Alzheimer’s disease research, genetics and epigenetics research, studies of animals and plants, population health studies, and aging research studies. They can come from just about everywhere in the life sciences. They can be inconsistent, pushing different viewpoints. The contributing scientists mostly do excellent work. But they don’t always talk with each other A tower of babel!
16 The context – State of the scienceUnderstanding aging takes us into just about every area of human biology and medicine The field is incredibly broad and deep It consists of many disparate areas of studies Most scientists are only partially aware of what other scientists producing related results are doing, and can be unaware that others have solved part of the problem that they are addressing. So, what is presented here is my own story of what is known about aging
17 Our challenge (Aging Sciences)Pulling together important current research results from diverse fields and interpreting them from the viewpoint of aging Publishing in-depth articles on key topics in our blog An 8-year undertaking, so far, nearly 500 in-depth articles 6,000 – 8,000 daily readers
18 CONSEQUENCES OF AGING
19 We know a lot about the consequences of agingIt is fatal We are living longer Survival curve is becoming rectangular Image source Yet, everybody dies by age 122
20 The life expectancy curve is being rectangularizedImage source Social security act passed 1935 Average US life expectancy 64 Now. Average US life expectancy 80
21 We know a lot about the consequences of agingEfficiency and regulation of key body systems declines with advancing age Stem cell senescence and decreased cell differentiation capability lessened immune responses Decline in key hormones Decreases in numerous key proteins Decreased antioxidant defenses Decreased DNA repair capabilities
22 We know a lot about the consequences of agingMetabolic pathways less efficient DNA gets methylated Histones get deacetylated Molecular signaling pathways becomes less efficient Activation of key health genes decreases Activation of cancer and other disease-related genes increases More and more DNA damage The list goes on and on Incremental deecripitude
23 Consequences of aging With declines there is a steep rise in susceptibilities to age-related diseases Cancers, cardiovascular diseases, diabetes, Alzheimer’s Disease, Parkinson’s Disease, etc. Alzheimer’s Disease Image source Image source
24 Consequences of aging With aging there is a steep rise in susceptibilities to age-related diseases, e.g. cancers Image source
25 Consequences of aging With aging, there is a steep rise in susceptibilities to age-related diseases Dementia Parkinson’s Disease Image source Image source
26 There is also generally a decline in capabilities, e.g. cognitiveImage source
27 The aged consume far greater health care resourcesCost of fall injuries by age group Image source Image source A growing world-wide problem Image source
28 AGING SUCKS !
29 WHAT CAUSES AGING?
30 What causes aging? There are at least 24 respectable scientific theories of what causes aging Here are a few of them – my top 14 in 2007
31 Aging theories – my 2007 starting listOxidative damage Cell DNA damage Tissue Glycation Lifofuscin accumulation Mitochondrial dysfunctionality Chronic inflammation Immune system compromise Neurological degeneration Declines in Hormone Levels Susceptibility to Cancers Susceptibility to cardiovascular diseases Telomere shortening Epigenomic transformations Cell senescence
32 Discovered later Dozens of other reasons for aging , e.g16. Age related declines in SIRT, NAD+, PGC1alpha, Nrf2, etc, expression 17. Age related increases in NF-kappaB, P66shc, GSK-3 beta expression 18. Proliferation of ANRIL DNA repeats and inserted segments 19. Mutations in non-coding DNA and micro RNAs 20. Age-related changes in microbiomes 21. Proliferation of circular RNAs 22. Age-related circadian dysregulation 23. Insufficient stress
33 About the theories of agingThey are not independent E.g., oxidative damage can foster tissue glycation which, together with programmed accumulation of INK4a can increase susceptibility to cancers Every week new research reveals more complex inter-relationships among the theories. They all define important ways for looking at aging From the viewpoint of wanting to slow, stop or even reverse aging, we can’t ignore any of them.
34 Aging, like the universe, has no center or single central cause
35 Epigenetics/EpigenomicsSOME RESEARCH AREAS WHERE THERE HAS BEEN SIGNIFICANT RECENT ADVANCEMENT AND DISCOVERY Molecular biology study of biology at a molecular level. Overlaps with biology, chemistry, genetics and biochemistry. Epigenetics/Epigenomics Critical information in DNA but not in the genes themselves Gene activation pathways Stress Management Lessons of long-lived species Stem cell science Induced pluripotent stem cells Adult somatic stem cells, autologous stem cells
36 Cross-species communications and interdependencies MORE SCIENTIFIC AREAS WHERE THERE HAS BEEN SIGNIFICANT RECENT ADVANCEMENT AND DISCOVERY Cross-species communications and interdependencies Roles of biomes - Microbes that lie with and affect us; the gut, the skin, in the soil, etc. Lessons of long-lived species Circadian regulation Lessons of centenarians, super-centenarians Data mining Systems biology Nanotechnology Liposomal supplement and drug delivery
37 Epigenetics/EpigenomicsNot very long ago we thought that once we sequenced the genes in the human genome we would be ready to understand biology, diseases and aging. After all, genes make our proteins, and that is what we are all about We were wrong
38 Epigenetics/EpigenomicsWe now know that the genes in the nucleus of a cell contain only a small portion of the information there. The rest of the information controls which genes are activated and when. It is called epigenetic information After all, all the cells in a body contain the same genes. And most of our genes are the same as those in mice or apes In both cases the differences are mainly due to which genes are activated Gene activation patterns change throughout life and with aging So, more and more researchers now grasp that we need to go far beyond genetics to epigenetics to understand what is going on in biology and aging.
39 Epigenetic information is encoded:In the long sequences of DNA between genes, once thought to be “junk DNA” (ncRNA coding) In how genes are silenced by being methylated In how tightly DNA is wrapped around the spindles (histones) in cells (histone acetylation) Compared to some 25,000 genes there are millions of epigenetic marks. Most remain unknown. Epigenetics is providing a whole new way of looking at biology, diseases and biology
40 SOME RESEARCH AREAS WHERE THERE HAS BEEN SIGNIFICANT RECENT ADVANCEMENT AND DISCOVERYMolecular biology study of biology at a molecular level. Overlaps with biology, chemistry, genetics and biochemistry. Epigenetics/Epigenomics Critical information in DNA but not in the genes themselves Gene activation pathways Stress Management Lessons of long-lived species; molecular stress pathways Stem cell science Induced pluripotent stem cells Adult somatic stem cells, autologous stem cells
41 Cross-species communications and interdependencies MORE SCIENTIFIC AREAS WHERE THERE HAS BEEN SIGNIFICANT RECENT ADVANCEMENT AND DISCOVERY Cross-species communications and interdependencies Roles of biomes - Microbes that lie with and affect us; the gut, the skin, in the soil, etc. Lessons of long-lived species Circadian regulation Lessons of centenarians, super-centenarians Data mining Systems biology Nanotechnology Liposomal supplement and drug delivery
42 Where are we in aging research? - OverallAMOUNT AND DEPTH OF DETAIL IS ASTOUNDING – A HUMAN IS BY FAR THE MOST COMPLEX ENTITY KNOWN IN THE UNIVERSE LIKE PUTTING TOGETHER A 30 MLLION PIECE MULTIDIMENSIONAL JIGSAW OF AGING AND THE PATHWAYS INVOLVED IN AGING
43 Where are we in aging research? - OverallWE ARE ASSEMBLING SUB CHUNKS OF THE PUZZLE WITHOUT KNOWING HOW THEY WILL ALL EVENTUALLY FIT TOGETHER WE DON’T HAVE A GUIDING PICTURE ON THE BOX COVER WE HAVE ENOUGH BIG SUBCHUNKS TO MAKE MANY OF US THINK THAT THE PUZZLE WILL BE COMING TOGETHER SOON WE ARE UNDERSTANDING MORE AND MORE ABOUT THE CONSEQUENCES OF AGING AND THE PATHWAYS INVOLVED IN AGING = AND WHAT TO DO TO LIVE LONGER HEALTHIER LIVES
44 Rubens: Defeating the aging monster?
45 PLEASE GO ON TO PART 2 OF The Prospects that Emerging Science Offers Us for Long Healthy Lifespans Actions and interventions for extending healthspan and lifespans – Focus on the personal and practical Vince Giuliano