Laboratory of Epidemiology, Demography and …Weight and height tend to increase with age, then...
Transcript of Laboratory of Epidemiology, Demography and …Weight and height tend to increase with age, then...
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Overview of Age-Related Changes in Physiology
Tamara Harris, M.D., M.S.Laboratory of Epidemiology, Demography and
BiometryNational Institute on Aging
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Weight and height tend to increase with age, then decrease
Body fat increases even if weight is constantCentral fat, particularly visceral fat, increases with ageLean mass decreases with age as does boneBoth tissues are increasingly infiltrated with fat with age
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BUT!!Few consistent problems secondary to age-related liver changes
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Renal function declines with age
Can be estimated from serum creatinineExacerbated by hypertensive diseaseMay affect clearance of supplementsBUT!!Few consistent problems identified
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Little known about effects of non-alcoholic fatty liver
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Major age-related problem is due to lack of communication:
Patients don’t tell their health care provider they are takingsupplements unless the health care provider asks!
Why don’t patients tell?- doctors are prejudiced or not knowledgable- don’t want to admit to unconventional therapies- reason for use seen as unrelated to care- not consider supplements to be “drugs”
Other factors mentioned in earlier presentations….
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Herbal Medicines and Perioperative CareAng-Lee et al. JAMA 2001;286:208
Echinacea – ImmunosuppressiveHepatotoxic
Ephedra -- SympathomimeticHalf-life 5 hours – urine-excreted
Garlic -- Platelet functionStop 7 days prior to surgery
Gingko -- Platelet function among othersStop 36 hours prior to surgery
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Herbal Medicines and Perioperative CareAng-Lee et al. JAMA 2001;286:208
Ginseng -- Platelet function among othersStop 7 days before surgery
Kava -- Sedative/hypnoticHalf-life 9 hours –urine/fecesStop 24 hours before surgery
Valerian -- Sedative-GABA receptor drugspotentiated - ?withdrawal
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St. John’s wort – putative antidepressant
Liver function
CYP4503A4 induced – doubling metabolic activity
Lidocaine, calcium channel blockers, serotonin receptor antagonists
CYP4502C9 induced -- reduces anticoagulant effects of warfarin, interferes with other NSAIDS
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Where do people get their information?
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AGING TODAY: Homogeneity VERSUS Heterogeneity
“If you’ve seen oneold person, you’ve seen one old person”
VSAGE 65+
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OutcomesLife course SUCCESSFUL
Co-morbiddiseases
Lots of drugs!DisabilityDeath
GenesEnvironmentPersonal habits
SmokingAlcoholExercise
USUAL
FRAIL
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1 2 3 4 5 61.4
1.6
1.8
2.0
2.2
2.4
2.6
2.8
1 2 3 4 5 6 7 81.4
1.6
1.8
2.0
2.2
2.4
2.6
2.8 IADLs
Katz ADLs
Med
ian
IL-6
Plas
ma
Leve
l(p
g/m
L)M
edia
n IL-
6 Pl
asm
a Le
vel
(pg/
mL)
Rosow-Breslau Nagi
Life Satisfaction Self-Rated Health
1 2 3 4 5 6
1 2 3 41 2 3 4
1 2 3 4
Median IL-6 Level According to Functional Status in the Duke EPESE(Cohen HJ et. al. The association of plasma IL-6 level with functional disability in community-dwelling elderly. Journals of Gerontology 1997; 52:M201-M208)
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IL-6 is a hallmark of inflammationAcute inflammation• Acute insult triggers molecular defenses including
High pro-inflammatory cytokines from macrophages and other cells
Acute phase activation - liver protein profile• Constitutional symptoms• Vital for health - resolution, death or chronic
Chronic inflammation• Milder form • Unresolved but controlled • Asymptomatic• Health benefits/detriments under investigation
Role in wasting/sarcopenia?Paradoxical risk factorsNovel risk factor disease/disabilty
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Inflammation and Health Outcomes in Old Age
dementiadiabetesarthritis
infections
periodontal dx
acute phase proteinscatabolism increased
pulmonarydisease
?
coagulationproinflammatorycytokines
poor healthoutcomessmoking
altered lipid profile?endothelial injury?smooth muscle cellproliferationinsulin resistance
?cardiovasculardisease
cerebrovasculardisease
?
(-)cancer
weight
NSAIDS, ASAantioxidantsglucorticoidsestrogen
(+)
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Research needs:
Studies of pharmacologic properties of new supplements
Emphasis on heterogeneity in older population, particularly on defining risks for frail
Study effects of age-associated conditions affectingliver including fatty liver disease and inflammation
Drug interactions with multiple co-medications
Better education programs for providers and patients to communicate the results of this research
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Continue search for effective supplements…..