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Aging and. Tract GAstrointestinal. What IS Aging?. Practically …. Aging = reduced tissue/physiological function. Aging = increased susceptibility to disease (age-related diseases). Aging = decreased resistance to stress (physical and psychological). Why do we age --- GENES.

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slide3

Practically ….

Aging = reduced tissue/physiological function

Aging = increased susceptibility to disease

(age-related diseases)

Aging = decreased resistance to stress

(physical and psychological)

slide4

Why do we age --- GENES

Genes determine species-specific

life span (LAGs)

(e.g., mice, monkeys, humans, tortoises)

Genes determine differences among

individuals within a species

(e.g., big/small noses)

(genetic polymorphisms)

slide5

Species-specific longevity genes

Flies (Drosophila melanogaster)

Nematodes (Caenorhabditis elegans)

Mice (Mus musculus)

Humans (Homo sapiens)

Galapagos turtles (Geochelone elephantopus)

Life spans ranging from 2-3 weeks to

100-200 years!

slide6

50 Years

18 Months

AGING in MICE AND MEN

MICE

HUMANS

Fitness Disease

(Cancer, osteoporosis, diabetes, etc.)

AGE (log)

Mice and Humans are 97% genetically similar!

slide7

Species-specific longevity genes

What are the genes that determine why

mice live <4 years, whereas humans

live >100 years?

Potentially big pay-off,

but complicated by development/evolution

slide8

Individual longevity genes

(polymorphisms)

Smaller pay-off,

but possibly amenable to intervention

(environment, life style, drugs??)

aging
Aging

Can we do Intervention.?

slide10

DIET

Eat well, but not too much!

Food ----> simple molecules

+ oxygen (mitochondria) ----> energy

FOOD ---> ENERGY

Oxygen metabolism ----> damaging byproducts

(ROS, oxidative stress)

Anti-oxidant defenses good, but not perfect

(different among species)

OPTIMAL food

= less ROS, less damage, more defenses

longer lifespans!

slide11

DIET

DIET

CALORIC RESTRICTION

GOOD NEWS!

30-40% calorie restriction

without malnutrition

extends HEALTHY lifespan 40-50%

(worms, flies, mice, rats -- maybe monkeys)

BAD NEWS!

Life SEEMS longer!!

(let's develop that CR pill)

slide12

EXERCISE

Yes, yes, yes ….. (but not too much)

Exercise ---> healthier muscles,

May be prevent telomere shortening .greater fitness

Greater protection from oxidative stress!

(not such a paradox, anti-oxidant defenses)

slide13

Think good thoughts!

Avoid undue stress

Physiological stress:

Stress hormones, a double edged sword

Physical stress:

Overwhelm cellular defense mechanisms

slide14

Why do we age ---

PAST ENVIRONMENT

Genes evolve in response to environment

This is REALLY why we age!

slide15

Aging before cell phones ……..

"Protected"

Environment

(climate control,

biomedical intervention

etc.)

100%

SURVIVORS

"Natural"

Environment

(hazards, predators,

infection, etc.)

HUMANS:

MICE:

4 mos

40 yrs

80 yrs

3-4 yrs

AGE

slide16

GOOD NEWS!

If we keep our "protected" environment,

we WILL evolve longer life spans!

BAD NEWS!

It's going to take a LONG time!

slide17

Sooo…. What's to be done about aging now?

Optimize present environment

New therapies on the horizon!

•Cell based therapies

•Drug based therapies

Support basic research in aging!

slide18

Individual longevity genes

Most identified so far are

disease-susceptibility genes

its role in several biological processes not directly related to lipoprotein transport, including Alzheimer's disease (AD), immunoregulation, and cognition.(e.g., ApoE4)

Solution = preventive drugs

Healthy centenarian studies are

underway!

Solution = ??????

slide19

Cell based therapies

Stem cells!

• embryonic

• adult

• nuclear transplant (cloning)

Telomerase!

• increase cell divisions

• anti-cancer therapy

slide20

Drug-based therapies

Anti-oxidants, mitochondrial protectors,

etc.

Hormones!

• growth hormone

• insulin/IGF (lessons from worms and flies)

• estrogen

CR mimetics!

aging definition
AgingDefinition

Aging is the progressive, universal decline first in functional reserve and then in function that occurs in organisms over

Aging is heterogeneous.

It varies widely in different individuals and in different organs within a particular individual.

Aging is not a disease; however, the risk of developing disease is increased, often dramatically, as a function of age.

The biochemical composition of tissues changes with age; physiologic capacity decreases, the ability to maintain homeostasis in adapting to stressors declines, and vulnerability to disease processes increases with age .

biology of aging
Biology of Aging

As we age, we become increasingly unlike one another. For any variable one can measure, the variation in the distribution of values in a population increases with age. While the mean value may trend up or down, the age-related increase in the range of values is striking testimony to the diverse manifestations of the aging process. In addition, homeostatic mechanisms are slower to respond to stressors and take longer to restore normal function as we age. The ability to maintain stable function in the face of a change in the environment is called allostasisand it declines with age.

demography of aging
Demography of Aging

Improvements in environmental (e.g., clean water and improved sanitation) and behavioral (nutrition, reduced risk exposures) factors and the treatment and prevention of infectious diseases are largely responsible for the 30-year increase in life expectancy since 1900.

In the United States, by 2030, 1 person in 5 will be >65 years.

global aging
Global Aging

At present 59% of older adults live in the developing countries of Africa, Asia, Latin America, the Caribbean, and Oceania.

The developed world has the largest absolute number of older adults and is experiencing the largest percentage increase.

gastrointestinal disorders
Gastrointestinal Disorders

Gastrointestinal (GI) disorders represent the third cause of consultations by general practitioners among subjects older than 65 years in Western countries.

gastrointestinal disorders1
Gastrointestinal Disorders

Age-related anatomical and physiologic changes occur in the major organ systems, affecting functions as diverse as swallowing and hepatic and renal clearance of therapeutic drugs. Because of these factors, and because older patients are more likely to be receiving multiple drugs for concomitant illness, they are more prone to drug-drug interactions and to medication-induced injury of the esophagus and stomach. In addition, several gastrointestinal disorders, notably gastroesophageal reflux and peptic ulcer disease, are commonly seen in the elderly.

J Clin Gastroenterol. 1991;13 Suppl 2:S65-75Bozymski EM, Isaacs KL

Department of Medicine, University of North Carolina, Chapel Hill 27599-7080

objectives
Objectives
  • Define age-related changes in the gastrointestinal tract
  • Discuss common G.I. problems associated with aging
  • Describe the risk factors for gastro-esophageal reflux disease
  • Describe the risk factors for peptic ulcer development
  • List the causes of diarrhea and fecal incontinence in the elderly
epidemiology
Epidemiology
  • Over 35 million people aged > 65 years in the United States
    • 12% of the 2003 US population were older than 65
      • 18.3 million aged 65-74
      • 12.9 million aged 75-84
      • 4.7 million aged ≥ 85
  • 35% to 40% of geriatric patients will have at least 1 GI symptom in any year
    • Common problems in this age group include constipation, fecal incontinence, diarrhea, irritable bowel syndrome (IBS), reflux disease, and swallowing disorders

Hall KE, et al. Gastroenterology. 2005;129:1305-1338.

He W, et al. 65+ in the US: 2005. US Census Bureau Web site. Available at: http://www.census.gov/prod/2006pubs/p23-209.pdf. Accessed 11/30/06.

the age wave

Increase in the Number of Persons

Aged 65+ Years in the United States

72

(20%)

Number (millions)

Percent of population

55

(16%)

40

(13%)

Population

35

(12%)

31

(13%)

26

(11%)

20

(10%)

17

(9%)

12

(8%)

9

(7%)

7

(5%)

5

(5%)

4

(4%)

3

(4%)

Year

The “Age Wave”

He W, et al. 65+ in the US: 2005. US Census Bureau Web site. Available at: http://www.census.gov/prod/2006pubs/p23-209.pdf. Accessed 11/30/06.

motility an gi tract
Motility an GI tract

Normal aging is associated with significant changes in the function of most organs and tissues. In this regard, the gastrointestinal More important is the impact of various age-related diseases on gastrointestinal motility in the elderly: for example, long-standing diabetes mellitus may reduce gastric emptying in up to 50% of patients; depression significantly prolongs whole-gut transit time; hypothyroidism may prolong oro-caecal transit time; and chronic renal failure is associated with impaired gastric emptying. In addition, various, frequently used drugs in the elderly cause disordered gastrointestinal motility. These drugs include anticholinergics, especially antidepressants with an anticholinergic effect, opioid analgesics and calcium antagoniststract is no exception.

gastrointestinal disorders2
Gastrointestinal Disorders

Available data allow the conclusion to be drawn that impaired intestinal motility, as evidenced by attenuated migrating motor complex activity, results in bacterial overgrowth.

slide47

GI Motility

pristalsism and Migratory

Myo electric

complex

gastrointestinal disorders3
Gastrointestinal Disorders
  • Heart disease, cancer, and stroke have become the leading "killers" among older adults, while deaths due to infection have decreased. Adults surviving into late life suffer from high rates of chronic illness; 80 percent have at least one and 50 percent have at least two chronic condition. There is a strong association between the presence of geriatric syndromes (cognitive impairment, falls, incontinence, vision or hearing impairment, low body mass index, dizziness) and dependency in activities of daily living
geriatric diseases of the upper digestive tract
Geriatric diseases of the upper digestive tract

During aging, secretion and motility of the upper GI tract slow down. The reduction of these functions, however, does not create complaints. In the higher age groups, a number of symptoms from age-dependent diseases occur more frequently, e.g., dysphagia in response to cerebral ischemia, or disturbed gastric emptying caused by diabetic visceral neuropathy. Moreover, certain GI diseases occur more often in the elderly, e.g., chronic atrophic gastritis, NSAR-induced gastric ulcers, malignancies, and others. In contrast, almost nothing is known about diseases or symptoms of the GI tract that might be specific for the elderly. With only a few exceptions, there are no age-dependent clinical differences. Nevertheless, intestinal diseases often develop more rapidly and the mortality is higher in the elderly than in younger people.

Z Gerontol. 1992 Sep-Oct;25(5):286-8.

age related changes in the gastrointestinal tract
Age-Related Changes in the Gastrointestinal Tract
  • Areas identified as important to aging are:
    • Pathophysiology of swallowing disorders
    • Esophageal reflux
    • Dysmotility symptoms
    • GI immunobiology
    • Cellular mechanisms of neoplasia in the GI tract
    • Decreased visceral sensitivity

Motility

Hormone

responsiveness

Visceral

sensitivity

Drug

metabolism

Liver sensitivity

to stress

Pancreas:

Structure

and function

Immunity

Lithogenic

bile

Colonic

function

Hall KE, et al. Gastroenterology. 2005;129:1305-1338.

esophageal aging
Esophageal Aging
  • Dysphagia, regurgitation, chest pain, heartburn- associated nausea are common in the elderly
  • “Presbyesophagus”: (age-related changes in esophageal function)
    • Decreased contractile amplitude
    • Polyphasic waves
    • Incomplete relaxation of the lower esophageal sphincter (LES)
    • Esophageal dilation
  • GERD
    • Common in the elderly
    • Impaired clearance of acid
    • Longer duration of reflux episodes
    • Atypical symptom presentation

Hall KE, et al. Gastroenterology. 2005;129:1305-1338.

aging and the stomach
Aging and the Stomach

Hall KE, et al. Gastroenterology. 2005;129:1305-1338.

Cullen DJE, et al. Gut. 1997;41:459-462.

nutrition
Nutrition
  • Geriatric patients, especially aged > 85 years, are at risk for decreased food intake due to several factors:
    • Mobility impairment
    • Ability to obtain food
    • Loss of taste, may be due to decreased olfaction
    • Poor dentition
    • Decreased appetite
    • “Anorexia of Aging,” may be related to neuroendocrine changes
    • Depression

Hall KE, et al. Gastroenterology. 2005;129:1305-1338.

gastrointestinal bleeding is common in the elderly
Gastrointestinal Bleeding Is Common in the Elderly
  • 75% GI bleeding in the upper tract
    • Esophagus
    • Stomach
    • Small bowel
  • 20%-25% GI bleeding in the lower tract
    • Terminal ileum
    • Colon
    • Rectum

Hall KE, et al. Gastroenterology. 2005;129:1305-1338.

gastrointestinal bleeding in the elderly
Gastrointestinal Bleeding in the Elderly
  • Of the 75% bleeding in the upper tract
    • 50% bleeding is due to NSAID use
    • 50% bleeding is due to ulceration or erosions (peptic or esophageal)
  • Females are at higher risk than males
  • Continued bleeding and rebleeding are the highest predictors of mortality and morbidity in older patients

Hall KE, et al. Gastroenterology. 2005;129:1305-1338.

Image courtesy of David C. Metz, MD.

colorectal cancer in the elderly
Colorectal Cancer in the Elderly
  • An estimated 106,680cases of colon and 41,930 cases of rectal cancer were expected to occur in 2006
  • 90% of all cases occur in individuals aged > 50 years

American Cancer Society. Cancer Facts and Figures 2006. Atlanta: American Cancer Society; 2006.

Burt RW. Gastroenterology. 2000;119:837-853.

Image courtesy of Subhas Banerjee, MD.

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