Aging

Question 1

What is the general vs specific view of aging?

Answer 1

General view: aging is the sum of all structural / functional changes occurring over time

Specific view: post-maturational period of decline in health (senesence), ultimately resulting in death

Question 2

What generally causes cellular aging?

Answer 2

Progressive decline in cellular function due to accumulation of cellular / molecular damage, especially genetic abnormalities

Question 3

What organism is ageless?

Answer 3

Bacteria

Question 4

On a survival curve, what is the maximum life span potential?

Answer 4

The time at which the last individual in the population dies (0% survival)

Question 5

What does life expectancy mean on a survival curve?

Answer 5

50% or median survival of a population / cohort

Question 6

What are the two shapes of survival curves, and which one do humans exhibit?

Answer 6

1. Exponential decline -> due to constant environmental hazards, a constant fraction dies overtime. Characteristic of “the wild”
2. Sigmoid decline -> diminishment of environmental hazards, characteristic of non-wild conditions (fraction dying changes overtime). This is a property of civilization = humans exhibit this. Shows the phenomenon of aging.

Question 7

Have LE and MLSP changed significantly overtime? Why?

Answer 7

LE - has increased. The median survival has grown higher and higher. This is thought to be a product of reduction in environmental hazards.

MLSP - seems to be intrinsic and based on senescence, has not changed overtime. Even 2000 years ago, there were some elders who lived as long as our oldest people. (species-specific).

Question 8

What is the mode of inheritance of Hutchinson-Guilford syndrome, what is it also called, and what is the nature of the defect?

Answer 8

Infantile progeria syndrome -> defect in lamin A gene, a nuclear membrane protein.

Autosomal recessive

Average life expectancy is about 12 years

Question 9

What is the mode of inheritance of Werner syndrome, what is it also called, and what is the nature of the defect?

Answer 9

Adult progeria syndrome
-> defect in DNA helicase gene, involved in DNA repair and recombination

Autosomal recessive

Average life expectancy is about 40 years

Question 10

Are progeria syndromes identical to normal aging?

Answer 10

No, there are a lot of other pathological processes going on, but certainly there are shared features.

Question 11

What did the Hayflick experiments demonstrate?

Answer 11

The number of doublings of fibroblast-like cells is finite, and is followed by deterioration.

Organisms with greater possible fibroblast doublings tended to have a longer lifespan

Question 12

After about how many divisions are telomeres lost?

Answer 12

~50

Question 13

What are sirtuins and what are a few of their functions?

Answer 13

NAD-dependent protein deacetylases

Function in DNA repair, gene expression, apoptosis, and aging
-> have a protect effect against DNA damage via deacetylation of proteins which are active to cause DNA dysfunction

Question 14

What is the mechanistic basis for dietary caloric restriction reducing certain age-related diseases?

Answer 14

A reduction in oxidative metabolism reduces the rate of oxidative / free radical damage

• > longevity
• > some theory that we may have a maximum lifetime energy usage allowance

Question 15

What piece of evidence seems to imply that acquiring, processing, and transmitting knowledge is useful to overall survival of the species?

Answer 15

Brain size directly correlates with longevity

Question 16

What do genomic mechanisms of aging suggest?

Answer 16

Specific aging genes, including genes which control cell doubling (telomerase), apoptosis, and gene regulation sirtuins, control the ultimate senescence of the organism.

Question 17

What is the somatic mutations theory?

Answer 17

A wear and tear mechanism of aging, which suggests that cumulative DNA damage from processes such as radiation or chronic insult leads to impairment of cell / organism survival.

Question 18

What are wear and tears mechanisms of aging?

Answer 18

Aging occurs through the accumulation of damage due to random events, i.e. free radicals, glycosylation, etc

Question 19

What are the regulatory system mechanisms of aging based on?

Answer 19

Aging occurs due to dysfunction in one of the major organ systems, which acts as sort of biological clock

Question 20

What is the immunologic system theory?

Answer 20

Changes in immune system lead to abnormal immune function, increasing incidence of autoimmune disease and neoplasms
-> form of regulatory system mechanism

Question 21

What is the neuroendocrine model of aging?

Answer 21

HPA axis controls aging, based on the idea that puberty is on a biological clock
-> thus far, the “pacemaker” or “timekeeper” is yet to have been found.

Question 22

Based on the rate of living / metabolic energy theory, what governs how long you live?

Answer 22

Lifespan energy potential (LEP) -> MLSP is proportional to the amount of energy which can be consumed by the organism during its lifetime

Question 23

What is an age-related vs age-dependent disease?

Answer 23

Age-related = increases in frequency with aging, but not directly caused by it

Age-dependent = diseases related directly to effects of age / chronic exposures

Question 24

What are some age-related diseases?

Answer 24

Atherosclerosis / CVD, septicemia, pnuemonia, cancers, Alzheimer’s and Parkinson’s

Question 25

What are some age-dependent diseases?

Answer 25

Osteoporosis, osteoarthritis, cataracts, BPH / prostate cancer, temporal arteritis

Question 26

What are primary aging changes and give a few examples?

Answer 26

Non-disease conditions which happen uniformly in all aging people, occur gradually, and are irreversible

• > menopause, wrinkles, gray / loss of hair, lipofuscin accumulation
• > may occur at different times for different people due to environmental exposures

Question 27

What are some broad classes of physiologic aging changes, and what percentage change is thought to happen per decade?

Answer 27

5-10% decline in function per decade, past age 30

Classes: Changes in body composition (decreased tissue water), alterations in cardiovascular and immune function, neuroendocrine / metabolic changes, reduction in brain size