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OAIC Annual Meeting Plenary Session Age and Sex are THE drivers of - - PowerPoint PPT Presentation
OAIC Annual Meeting Plenary Session Age and Sex are THE drivers of - - PowerPoint PPT Presentation
OAIC Annual Meeting Plenary Session Age and Sex are THE drivers of most diseases and chronic conditions Age and Sex are THE drivers of most diseases and chronic conditions Claude D. Pepper Older Americans Independence Centers (OAIC) The goal
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Age and Sex are THE drivers of most diseases and chronic conditions
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Claude D. Pepper Older Americans Independence Centers (OAIC) The goal of the OAIC program is to increase scientific knowledge that allows older adults to maintain or restore their independence.
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83 years old; HTN, Hyperlipidemia, prior MI 83 years old; HTN, Hyperlipidemia, prior MI
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A new paradigm – address the most common risk factor for all chronic disease simultaneously, and translate it into HEALTHspan
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Part 1
Interventions that address aging: success in animal models
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Proteostasis Epigenetics Macromolecular Damage Inflammation Other Biology Metabolism Stem Cells Stress Response
López-Otín et t al. Cell 153:1194 (2013) Sierra & Kohanski J Gerontol June 2014
Conceptualization: Mechanism of Aging
Slide courtesy Felipe Sierra, PhD
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Proteostasis Epigenetics Damage Inflammation Other Biology Metabolism Stem Cells Osteoporosis Sarcopenia Frailty Vision Diabetes Dementia CKD Arthritis
Chronic Disease
COPD Neurodegeneration Stress Adaptation Hearing
Aging mechanisms link to the development of chronic disease
CVD
Slide courtesy Felipe Sierra, PhD
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Major advances in lifespan and healthspan improvements-animal models
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Senescence Associated Secretory Phenotype ( SASP) – strongly pro-inflam m atory!!
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Part 2
Translating anti-aging approaches to humans to improve healthspan
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How will we test the hypothesis that anti-geronic approaches enhance healthspan in humans?
Slide courtesy Steve Kritchevsky
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The Problem of Biomarkers in Aging Research
Slide courtesy Steve Kritchevsky
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Epigenetics:
CHANGES IN METHYLATION AT CPG SITES ALTER GENE EXPRESSION WITHOUT CHANGING THE INHERITED GENETIC CODE. METHYLATION PATTERNS CAN BE USED TO PREDICT A PERSON’S CHRONOLOGIC AGE
(S. Horvath Genome Biol. 2013)
METHYLATION PATTERNS ARE ALSO BEGINNING TO REVEAL DIFFERENCES BETWEEN CHRONOLOGIC AND BIOLOGIC AGE
(Rickabaugh et al. PLoS One 2015)
( Katerina Karavodin)
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DNA Methylation – may be the single best marker
- f “passing time,” i.e. Chronologic Age
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DNA Methylation and Age Verified in nearly all tissues
(prostate, head & neck, cartilage?)
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HIV-1-infection accelerates epigenetic aging
Using a multi-variate model that includes methylation patterns, age, and HIV status, Rickabaugh, et al. estimated that HIV-1- infection accelerates aging by ~14 years in ART naïve MACS participants
- Rickabaugh et al. PLoS
One 2015 All from the MACS cohort
- 24 samples from 20–24 year olds
- 24 samples from 48–56 year olds
- In each group, 12 were HIV-1 seropositive
men and 12 were HIV-1 seronegative men
- Avg BMI similar, Hep B/ C status similar
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What do integrative functional assessments add?
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Examples of Functional “biomarkers”
- Multi-morbidity/Cumulative deficit scores
– Rockwood, VACS (for HIV)
- Physical function
– Gait speed, grip strength, SPPB/other composite functions, 6 min walk distance
- Cognitive function/reserve
– MOCA, many others
- Vulnerability/Resilience
– Fried Frailty Index, Resilience (Psychosocial)
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Gait Speed and Survival in Seniors
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Death and Disability Rate by Modified Physiologic Index score: The Health ABC Study
Sanders J L et al. J Gerontol A Biol Sci Med Sci 2012;67:1439-1446
Score based on tertiles of: 1. Systolic Blood Pressure 2. Forced Vital Capacity 3. Digit Symbol Substitution Test 4. Cystatin-C and a priori cut-points of 5. Serum Fasting Glucose (<126; 126-142,≥142)
Slide courtesy Steve Kritchevsky
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