Biology of Aging

Question 1

What is aging?

Answer 1

• not clearly defined
• time-related deterioration of the physiological functions necessary for survival and reproduction

Question 2

What is longevity?

Answer 2

The length of the lifespan independent of aging

Question 3

What are damage theories of aging?

Answer 3

Aging is caused by the cumulative impact of environmental assualts over the lifecourse

Question 4

What are some examples of damage theories?

Answer 4

• wear and tear theory
• rate of living theory
• cross-linking theory
• free-radical theory
• somatic DNA damage theory

Question 5

What are program theories of aging?

Answer 5

Aging follows a biological timetable which may be a continuation of development programs of fetal life and childhood

Question 6

What suggests that aging may be pre-programmed genetically?

Answer 6

• single-gene mutation disorders which have characteristics of accelerated aging
• e.g. Hutchinson-Guilford Progeria syndrome

Question 7

What are some examples of program theories?

Answer 7

• programmed longevity
• endocrine theory
• immunological theory

Question 8

Which theories of aging are more widely accepted?

Answer 8

Damage theories

Question 9

What is meant by the term ‘Hallmarks of Aging’?

Answer 9

• common characteristics of aging across multiple species
• aims to identify biological pathways which contribute to aging

Question 10

Which criteria must be met in order to qualify as a hallmark of aging?

Answer 10

• manifests during normal aging
• its experimental aggravation should accelerate aging
• its experimental removal should slow the normal aging process and therfore increase healthy lifespan

Question 11

What are genomic hallmarks of aging

Answer 11

• hallmarks concered with changes in gene structure or expression
• genomic instability
• epigenetic changes
• telomere attrition

Question 12

How does genomic instability lead to aging?

Answer 12

• there are changes in copy number, chromosome stability, nuclear architecture and mitochondrial DNA
• failure to remedy these changes leads to cellular dysfunction which contributes to aging

Question 13

How do epigenetic changes lead to aging?

Answer 13

• aging is associated with loss of DNA myelination, histone modification and changes in enzymes which regulate DNA packaging
• leads to inappropriate gene expression
• causes impaired DNA repair and chromosomal instability

Question 14

How does telomere attrition lead to aging?

Answer 14

• telomeres cannot be replicated fully in DNA replication in most cells
• shorten with each round of replication
• once they reach a certain length the cell stops dividing (senescence)
• loss of telomeres with age leads to cellular senescence and inabilty to maintain homeostasis, leading to aging

Question 15

What are the cellular hallmarks of aging?

Answer 15

• changes in cell behaviour or function over the lifecourse contributing to aging
• stem cell exhaustion
• changes in cell signalling
• cellular senescence?

Question 16

What is stem cell exhaustion?

Answer 16

• stem cell function decreases with age
• less able to contribute to repair and maintaenance of tissues
• also accumulate mutatuions leading to neoplasia formation

Question 17

How do changes in cell signalling lead to aging?

Answer 17

• more cells become senescent with aging
• senescent cells induce senescence in adjacent cells via cell signalling through gap junctions (bystander effect)

Question 18

How does cellualr senescence contibute to aging?

Answer 18

• aged senescent cells don’t get replaced as often
• increases demand for replacement cells which exhausts the stem cells
• senescent cells also secrete pro-inflammatory cytokines

Question 19

What are the biochemical hallmarks of aging?

Answer 19

• changes in cellular metabolism or biochemistry which contribute to aging
• impaired mitochondrial function
• impaired proteostasis
• impaired nutrient sensing

Question 20

How does impaired mitochondrial function contribute to aging?

Answer 20

• aging leads to loss of respiratory efficacy
• less energy is available for cellular processes
• mitochondrial dysfunction also leads to increased reactive oxygen species which damages cells

Question 21

How does impaired proteostasis contribute to aging?

Answer 21

• proteostasis ensures normal folding and maintenance of proteins
• if proteins are unfolded they are usually cleared by autophagy or breakdown by the proteosome
• aging leads to impaired clearing of unfolded proteins
• their aggregation disrupts normal cell function

Question 22

What is the evidence for impaired nutrient sensing contributing to aging?

Answer 22

• impaired function in GH and IGF-1 increases lifespan and healthy aging
• dietary restrictions can extend lifespan

Question 23

What is the information theory of aging?

Answer 23

Acquisitions of epimutations over the course of life leads to aging through the loss of youthful epigenetic information

Question 24

What can be done to treat biological aging?

Answer 24

• targeting the hallmarks of aging
• stem-cell therapies
• anti-inflammatories
• elimination of damaged and senescent cells
• telomerase reactivation
• epigenetic drugs
• dietary restrictions
• mitochondrial treatments