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Flashcards in Mechanism of Aging Deck (37):
1

Define aging

failure to maintain homeostasis under conditions of physiological stress accompanied by a decreased viability and increased vulnerability of the individual

2

True or false? aging is the most important risk for most chronic diseases

true

3

This is a group of effects which lead to a decreasing expectation of life with increasing age

senescence

4

In recent history, the documented age of human has not exceeded ____ years, which means it's probably an upper limit for natural aging

122

5

Studies have suggested that life-span is determined ___-___% by genetics

30-35

6

Organisms as diverse as fruit flies and monkeys when placed on calorie restricted diets show up to a ___% increase in maximum life spans

50

7

The ____-__ mutant of C. elegant has maximum life-span increased by 100% due to having a slower metabolism

age-1 (single gene mutation in PI3 Kinase homolog)

8

In mice, caloric restriction coupled with an insulin/IGF pathway mutation can ____ lifespan

double

9

Fibroblasts having a limited proliferative capacity in vitro of about 50 population doublings is known as the ____ limit

Hayflick

10

Describe the error or "wear and tear" hypothesis of aging

damage to cellular structure eventually leads to cell death

11

Describe the programmed cell death hypothesis of aging

senescence inducing genes limit life span of cells

12

A strong correlation exits between metabolic rate and rate of aging in certain species. Cold blooded species show ____ life span when metabolic rate is decreased by temperature

increased

13

In regards to waste product accumulation, this is non-enzymatic glycosylation of long lived proteins which leads to oxidized, cross linked products which accumulate within cells as they age.

lipofuscin

14

Damage to DNA accumulates with age due to inadequate DNA repair processing with age. This increases the incidence of _____

cancer

15

Free radicals have been thought to be correlated with aging. Where are most free radicals generated?

mitochondria

note: cellular functional impairment occurs when oxygen radicals overwhelm natural cellular antioxidant defenses

16

True or false? current evidence supports anti-oxidant supplementation as a major means to prevent age-related pathology

false; it does NOT support this

17

This is the enzyme responsible for synthesizing telomeres. This enzyme is present in the germ cell line, but not somatic cells

telomerase

18

Overexpression of telomerase in mice increases lifespan, but only in ____-resistant mice

cancer

19

Oxidative phosphorylation declines with age. True or false?

true - mitochondria function declines with age

20

Overexpression of mitochondrial catalase in mice leads to a 20% _____ in maximum life span

increase

note: supports mitochondrial function (oxidative phosphorylation)

21

Autophagy - cellular self-digestion (supply nutrients and remove damaged proteins) ____ with aging

declines

22

Proponents of this hypothesis say aging is just an extension of the developmental program - a death program that kicks in during the post-reproductive years

program hypothesis

23

What is the problem with the program hypothesis?

there can be no genetic selective advantage to decreased or increased lifespan for post-reproductive age

24

What mutation causes Werner's syndrome and how does it present?

mutation: DNA helicase

symptoms: gray hair before 27, bilateral cataracts, osteoporosis, death by late 40's

25

What mutation causes Hutchison-Gilford Progeria Syndrome and how does it present?

mutation: lamin A - nuclear structural gene involved in chromosome maintenance/DNA repair

symptoms: stroke or heart attack by 13, children resemble aging traits of an 80 yo

26

_____ is produced in the liver in response to growth hormone secretion from the pituitary gland It activates a signaling pathway that inactivates FoxO TFs

IGF-1

27

IGF-1 mutants seem to be linked to protection of mitochondria from ____ ____

oxidative damage

28

_____ is a major complex of proteins which monitors nutrients and stress in the cell

TOR

29

TOR kinase regulates proteins synthesis in the cell in response to stress and nutrient levels. TOR kinase inhibition is linked to what?

increased longevity

30

AMP kinase is a nutrient and energy sensor that represses ____ pathways when the cell's AMP/ATP ratio rises

anabolic

31

AMP kinase acts on _____ TF's which regulate energy metabolism and longevity

FoxO

32

_____ activates AMP kinase and can extend lifespan in mice

Metformin

33

This group of proteins are linked to regulation of metabolism due to the fact that they have NAD-dependent deacetylase activity. They regulate genes linked to switches in metabolism and their activity changes during aging.

Sirtuins

34

Humans have ___ SIRT genes

7

35

SIRT 1 is linked to what?

IGF-1, autophagy, and mitochondria biosynthesis

36

Chronic inflammation plays a role in the progression of age related diseases. ____ cells secrete interleukins

Senescent

37

Which vitamin has multiple anti-aging qualities?

Vitamin D