Biology Of Aging

Question 1

Aging?

Answer 1

Represents a time-dependent decline in physiological function

Question 2

Longevity and aging?

Answer 2

Distinct
Longevity - length of lifespan independent of aging

Question 3

Damage theories?

Answer 3

Cumulative impact of assaults over the life course causes aging

Question 4

Damage theory examples? We R ChieFS

Answer 4

Wear and tear theory
Rate of living theory
Cross-linking theory
Free-Radical theory
Somatic DNA damage theory

We R ChieFS

Question 5

Wear and tear theory?

Answer 5

Over time the components of cells and tissues eventually wear out, leading to the aging of the organism

Question 6

Rate of living theory?

Answer 6

An organisms rate of basal METABOLISM determines its lifespan - the higher the basal metabolism, the shorter the lifespan (eg rodents vs humans)

Question 7

Cross-linking theory?

Answer 7

Accumulation of cross-linked proteins over time impairs cellular function, slowing down bodily processes and leading to aging

Question 8

Free-Radical Theory?

Answer 8

Reactive oxygen species (ROS) cause damage to cellular macromolecules, (DNA, proteins) and organelles, impairing function. Accumulation of this damage over time results in aging

Question 9

Somatic DNA damage theory?

Answer 9

Genetics MUTATIONS are acquired faster than they can be repaired. These accumulate over time leading to a breakdown of genetic integrity, resulting in aging

Question 10

Program theories of aging?

Answer 10

Aging follows biological timetable - might be continuation of the growth and development programmes of fetal life and childhood

Question 11

Program theories of aging examples?

Answer 11

Programmed longevity
Endocrine theory
Immunological theory

Question 12

Programmed longevity?

Answer 12

this suggests that aging arises due to time-dependent changes in expression of key genes involved in growth or development.

Question 13

Endocrine theory?

Answer 13

this suggests that hormonal influences (eg GH-IGFI signalling) constitutes a biological clock that determines the rate of aging of an organism

Question 14

Immunological theory?

Answer 14

this suggests that progressive loss of immune system activity with increasing age leads to cellular stress and eventual death from impact of disease

Question 15

Genomic hallmarks?

Answer 15

concern changes in gene, chromosome or genome structure or expression, changes in the epigenome, that result in cellular dysfunction, leading to aging.

Question 16

3 genomic hallmarks?

Answer 16

1. Genomic instability
2. Epigenetic changes
3. Telomere attrition

Question 17

Genomic instability?

Answer 17

DNA damage accumulated -> mutations and premature aging syndromes
indicates link between aging and genetic integrity
Changes in copy number and chromosome stability in DNA observed with increasing age, as well as changes in nuclear architecture

Question 18

Epigenetic changes?

Answer 18

Aging associated with distinct Epigenetic changes:
-loss of DNA methylation
-age-specific patterns of histone modification
-changes in expression of enzymes that regulate DNA packaging and chromatin remodelling

cause transcriptional noise and changes in packaging and accessibility of DNA

Question 19

Transcriptional noise?

Answer 19

Inappropriate expression of genes
part of Epigenetic changes hallmark

Question 20

Telomere attrition?

Answer 20

Loss of telomeres over lifecourse thought to lead to cellular senscence and an inability to maintain homeostasis in tissues -> aging

telomerase - can maintain telomere length which can modulate mammalian lifespan

Question 21

Cellular hallmarks?

Answer 21

Relate to changes in cell behaviour or function over lifecourse -> aging through failure to maintain or repair tissues or organs

Question 22

Cellular hallmarks examples?

Answer 22

1. Stem cell exhaustion
2. Changes in cell signalling
3. Cellular senscence

Question 23

Stem cell exhaustion?

Answer 23

Decline in regenerative potential
Less cell division, less repair and maintenance of tissues, neoplasia formation

Question 24

Changes in cell signalling?

Answer 24

Age-related changes in inflammation, hormonal changes, and reduced immune system activity
Manipulation of signalling pathways may allow aging inhibition
senescent cells can influence cells around them to enter senescence too through communication via gap junctions

Question 25

Cellular senescence?

Answer 25

Senescence - stable arrest of cell cycle - in DNA damage -> prevents ongoing proliferation Senescence cells secrete pro-inflammatory cytokines In aged cells, senescence still occurs but stem cell activity is less efficient

Question 26

Biochemical hallmarks?

Answer 26

Relate to cellular changes in metabolism or biochemistry -> cell damage and dysfunction -> aging

Question 27

Biochemical hallmarks examples?

Answer 27

1. Impaired mitochondrial function 2. Impaired proteostasis 3. Impaired nutrient sensing

Question 28

Impaired mitochondrial function?

Answer 28

Loss of efficacy of respiratory train with aging -> less energy for cellular processes Mitochondrial dysfunction with aging -> increased ROS -> damage cellular macromolecules Accumulated mtDNA -> reduced bioenergetic -> decrease in cellular processes and aging

Question 29

Impaired proteostasis?

Answer 29

Proteostasis - controls normal folding and maintenance of proteins in folded state through chaperone activity Persistence of unfolded proteins -> aggregation = disrupted normal cell function (associated with age related disorders e.g. Alzheimer’s, Parkinson’s)

Question 30

Impaired nutrient sensing?

Answer 30

Mutations that impair function of activity of GH - IGF1 pathway = increased lifespan and healthy aging However, very low GH-IGF1 signalling incompatible with life