The Aging Brain Seminar Lecture I: The Problem of Aging

1. The Aging Brain SeminarLecture I: The Problem of Aging Timothy R. Jennings, M.D., DFAPA Author: Could It Be This Simple? The God-Shaped Brain The Journal of the Watcher The Remedy NT The God-Shaped Heart The Aging Brain: Proven Steps to Prevent Dementia and Sharpen Your Mind Past-President Tennessee Psychiatric Association Past-President Southern Psychiatric Association www.comeandreason.com

2. Objectives 1. Describe aging, what it is and what happens as we age. 2. Identify early life risk factors that accelerate aging. 3. Examine the impact our beliefs and thought patterns have upon the brain, and discover methods to reduce risk of dementia.

3. Disclosure/Resource

4. Risk Factors – A Metaphor • Many risk factors–but don’t be overwhelmed • Consider metaphor of keeping your car in to shape the risk factors of breakdown or accident

5. Risk Factors – A Metaphor • Driving a poorly constructed vehicle—being born with genetic or epigenetic vulnerabilities to aging • Driving a vehicle in poor condition—persons who don’t exercise or fail to maintain healthy nutrition • Driving a vehicle with defective or worn out brakes—people who have impaired ability to calm themselves or slow themselves down • Driving a vehicle with bald tires—overly emotional individuals who are not grounded in reality and who easily slip and slide as the emotional weather changes

6. Risk Factors – A Metaphor • Distractions such as texting, changing the radio station, or other people in the vehicle—caught up in entertainment, alcohol, drugs, addictions such that one doesn’t attend to their health • Poor vision—lack of education, insight, or understanding • Wet, snowy, or icy conditions—toxins, pollution, industrial exposures that accelerate aging • Purposeful sabotage—victims of abuse, war, and crime • Sleeping at the wheel—failure to listen and learn, ignoring healthy guidance when presented

7. Risk Factors – A Metaphor • Addressing 1 or more risk factors does not guarantee our cars will never break down or we will never have an accident, but it reduces the risk • Nor does having one or more of these problems mean we are certain to get into an accident or have a breakdown, but the more factors the greater the risk • So too with aging and risk of dementia

8. What is Aging? • Chronologically growing older? • Functionally growing older? • Slow decline in vitality and ability • We all move through time at the same rate—but we don’t all age at the same rate

9. Understanding Design Law • Principles, protocols, upon which life is built to operate—laws of health • Why don’t you put water in the tank of your car • This type of thinking is counter to human organizations—they impose laws • Immature think—its okay to smoke tobacco or marijuana as long as it is legal • The mature recognize legalizing it doesn’t make it healthy • It is not possible to be healthy in violations of the laws of health

10. Risk factors increase over time

11. 2nd Law of Thermodynamics • Entropy – if energy isn’t put into a system it slowly decays • Leave your home for 20 years and return • Allow a car to sit for 20 years • Human genome??? • If mankind is disconnected from God, is there a slow, gradual entropy to our genome? • Are we degrading or evolving to higher forms? • The Bible says that when Adam sinned, “dying you will die.”

14. Human Genome • An instruction manual containing a library of information • DNA molecules = letters • Clusters of these molecules = words • Words group to form genes = chapters • Chapters/genes group into Chromosomes = volumes • Volumes/Chromosomes group into genome = library containing 3.2 Billion base pairs in 23 pairs of chromosomes or 46 chromosomes

15. Genetic Entropy Mutation Type Mutations per person per generation <1 100-300 100-300 2-6% (plus) 2-6% (plus) Numerous Thousands? > 1000 • Mitochondrial • Nucleotide substitution • Satellite mutations • Deletions • Duplications/insertions • Inversions/translocations • Conversions • Total/person/generation

16. Genetic Mutations • A person at 65 will have in their DNA up to 6000 point mutations that were not there at birth • Each generation receives up to 1000 new mutations that the previous generation did not start with. • There has not been one mutation found that has actually added genetic information or improved the species • The human genome is slowly degrading

17. Chromosomes lose telomeres Risk factors increase over time

18. Telomeres

19. Telomeres • 1965 – cells with short telomeres didn’t divide in culture • 1990 – each time a human cell divides the telomeres shorten until cannot divide • 2006 – People with mood d/o’s have shorter telomeres • 2011 – institutionalized children have shorter telomeres • 2012 – telomere length predicts remaining lifespan http://psychnews.psychiatryonline.org/doi/full/10.1176/pn.47.17.psychnews_47_17_18-a

20. Telomere Length Declines in Dividing Cells as We Age Telomere Length in Base Pairs (Human Blood Cells) AGE (Years)

21. Telomeres • Shorter in males than females (but not at birth) 1 • Heredity accounts for 80% environ 20% • Negative effect • Childhood adversity 2 • Mood disorders • Hostility 1.Okudo, K., et al., Telomere Length in the Newborn, Pediatric Research (2002) 52, 377–381 Shalev, I., et al., Exposure to violence during childhood is associated with telomere erosion from 5 to 10 years of age: a longitudinal study, Molecular Psychiatry (2013) 18, 576–581; doi:10.1038/mp.2012.32; published online 24 April 2012

22. Telomeres • Positive effect • Healthy Diet— • Doubling the amount of carotenoids lengthened telomeres by 2% 1 • Carotenoids --highest levels had telomeres 5-8% longer 1 • Plant based diet increased telomerase acitivity2 • Older father when conceived 3 • Exercise 4 Kyoung-Bok Min, Jin-Young Min, European Journal of Nutrition April 2017, Volume 56, Issue 3, pp 1045–1052. Ornish, D., et al., Effect of comprehensive lifestyle changes on telomerase activity and telomere length in men with biopsy-proven low-risk prostate cancer: 5-year follow-up of a descriptive pilot study. The Lancet Oncology Volume 14, Issue 11, October 2013, Pages 1112-1120 Eisenberg DT, Hayes MG, Kuzawa CW. Delayed paternal age of reproduction in humans is associated with longer telomeres across two generations of descendants. PNAS USA. 2012;109:10251–6. Sjögren, P; Fisher, R; Kallings, L; Svenson, U; Roos, G; Hellénius, M (2014-09-03). "Stand up for health--avoiding sedentary behaviour might lengthen your telomeres: secondary outcomes from a physical activity RCT in older people.". Br J Sports Med48: 1407–9.

23. Percent of Newborns Living to 65 http://www.cdc.gov/nchs/data/ahcd/agingtrends/01death.pdf

24. Why are more people living longer over the last 100 years if the genome is deteriorating? • Reduced infections • Clean water • Safe food • Sanitation • Better nutrition • Vaccinations • Antibiotics • Improved dental care

25. Causes of Death • 1900’s 30% of all deaths from: • Pneumonia & Influenza • Tuberculosis • Diarrhea & Enteritis • 1990’s 60% of all deaths from: • Heart Disease • Cancer • Stroke http://www.cdc.gov/nchs/data/ahcd/agingtrends/01death.pdf

26. Causes of Death Today }Lifestyle • Cardiovascular Dz • Cancer • Stroke • Chronic lung Dz • Alzheimer’s Dz • Diabetes • Flu and pneumonia • Accidental injury • All other causes • 28.2% • 22.2% • 6.6% • 6.2% • 4.2% • 2.9% • 2.6% • 2.2% • 24.9% http://www.cdc.gov/chronicdisease/resources/publications/aag/aging.htm

27. What Contributes to Functional Decline as we Age?

28. Chromosomes lose telomeres Risk factors increase over time

29. Increases Inflammation Risk factors increase over time Chromosomes lose telomeres

30. Factors that Increase Risk of Dementia • Mindset – unhealthy beliefs • For as he thinks in his heart, so is he. (Prov 23:7 NKJV)

31. Expectations Mindset • 1979 – Men 75 years old • 1 week at a retreat, no material dated later than 1959 • 1 week they were to pretend it was 1959 • Given ID’s with their 55 y/o picture • Tested before and after: physical strength, posture, perception, vision, cognition, memory. • Results? Langer, E. (2009), Counterclockwise: Mindful Health and the Power of Possibility. New York: Ballentine.

32. Expectations Mindset • In every measure they improved • Greater flexibility • Better posture • Much improved hand strength • Eye-sight improved by 10% • Memory improved by 10% • More than half had improved IQ scores • Appeared younger • when before and after pictures were shown to random strangers Langer, E. (2009), Counterclockwise: Mindful Health and the Power of Possibility. New York: Ballentine.

33. Factors that Increase Risk of Dementia • Mindset – unhealthy beliefs • Social Security – fosters belief that productivity ends at 65 • We must educate that life doesn’t end at 65

34. NPTX2 Gene/Protein • Activates with new learning • Organizes and synchronizes brain circuits to form new memories • Turning this gene off makes one vulnerable to dementia • Keeping this gene on reduces dementia risk • What keeps this gene on? • Activity in the neurons—new learning—so retirement with the mindset of “I am done now” and nothing new to challenge…shuts this gene off and accelerates cognitive decline 1 1. Reti, IM, et al., Prominent Narp expression in projection pathways and terminal fields. J Neurochem. 2002 Aug;82(4):935-44.

35. Factors that Increase Risk of Dementia • Mindset – unhealthy beliefs • I’m no good…. • Trying to control outcomes/worry about future • Fear inducing God-constructs • Increased worry, stress, anxiety, fear • Activates brain’s fear circuitry • Increases inflammatory factors

36. Over active Amygdala • Activates sympathetic nervous system • Which activates macrophages – • Why? • Which release cytokines – IL1, IL6, TNF • Which damage: • Insulin receptors, glucocorticoid receptors, interfere with NE, 5HT, DA signaling • Resulting in: • Increased DM, obesity, high cholesterol, MI, Stroke, depression • All of which increase dementia Miller AH, et al. Biol Psychiatry. 2009;65(9):732-741.

37. Factors that Increase Risk of Dementia • Mindset – unhealthy beliefs • Dysfunctional relationships • Regardless of the source of the dysfunction (i.e. a child who is abused is not the source of the dysfunction but will still suffer damage from the dysfunction)

38. Animal Studies • Pups of nurturing mothers (licking/grooming) compared to pups of mothers who didn’t nurture • Pups without attentive mothers had altered brain development such that they had over active amygdalas and social impairments • When pups of neglect mothers were reared by nurturing mothers their brain development was the same as the pups of the nurturing mother

39. Child Abuse and Gene Expression in Brain Tissue • 41 Canadian men (25 severe abuse, 16 controls) • DNA examined from hippocampal neurons • 362 alterations in gene expression • Those most significantly affected where genes which regulated neuronal plasticity Arch Gen Psych, 2012; 69(7):722-731

40. Childhood Adversity Represents a Risk for Adulthood Disease 70 Number of Adverse Childhood Experiences 60 0 (n=502) 1 (n=253) ≥2 (n=98) 50 40 % of Study Members With the Condition 30 20 10 0 Panel 1: Major Depression Panel 2: hsCRP >3 mg/L Panel 3: Clustering of Metabolic Risk Markers 32-year prospective study. Major depression (panel 1): z=4.94, P<.001. High-sensitivity C-reactive protein (hsCRP) level  3 mg/L (panel 2): z=3.24, P=.001. Clustering of metabolic risk markers (panel 3): z=4.58, P<.001. 1 age-related disease risks (panel 4): z=5.66, P<.001. Adapted from Danese A, et al. Arch PediatrAdolesc Med. 2009;163(12):1135-1143.

41. Adults who were abused as children • Have higher rates of medical illnesses • Have higher rates of mental illnesses • Have higher suicide rates • Have higher alcohol/drug problems • Thus more disability and death • The Bible promise of long life for those with healthy family relationships is not magic or special divine intervention – it is the natural outcome of living in harmony with God’s design

42. Factors that Increase Risk of Dementia • Mindset – unhealthy beliefs • Dysfunctional relationships • Lack of spirituality/altruism

43. The Bible Teaches to Love & Love is Life • The entire law is summed up in a single command: “Love your neighbor as yourself.” Galatians 5:14 • Love “is not self-seeking” 1Cor 13:5 • In the way of righteousness there is life; along that path is immortality. Pr 12:28 • He who pursues righteousness and love finds life, prosperity and honor. Pr 21:21 • The law of the Lord is perfect, reviving the soul. Ps 19:7

44. WATER • image courtesy of chrusion | FX

45. www.comeandreason.com

46. Altruism Promotes Better Health • Adults who volunteer (after accounting for variables such as education, baseline health, smoking, etc.) • Live longer, have less illness, less disability, less depression, less dementia and live independently longer than those who did not.2 Post, S. Altruism and Health Perspectives from Empirical Research, Oxford University Press, New York, 2007: p. 22,26).

47. God Construct Changes Brain DLPFC ACC VMPFC Orbital PFC Pituitary Hypothalmus Amygdala Hippocampus Newberg, A. How God Changes Our Brain. Ballantine Books, New York. 2009: p.49. Illustration by Simon Harrison

48. REST GeneRepressor Element 1-Silencing Transcript • Cell Conductor – turning genes on and off • Impacts neuronal and brain circuitry development • Protects memory circuits—low levels increased risk of dementia • Turned off my chronic mental stress • Turned on by meditation and healthy spirituality 1 1. Ashton N, Hye A, Leckey C et al. Plasma REST: A Novel Candidate Biomarker of Alzheimer’s Disease Is Modified by Psychological Intervention in an At-Risk Population. Transl Psychiatry. June 6, 2017; 7(6): e1148

49. How Healthy Spirituality Helps Slow Aging • Activates PFC and ACC, calms amygdala, lowers inflammatory response resulting in improved mental and physical health • Altruistic activities result in better mental and physical health • Reduced anxiety and worry • Healthier lifestyle so reduced oxidative stressors • Healthier relationships lower stress

50. Two Grand World Views: Belief Systems • Godless origin of life? • Intelligent God created life?