Biology Of Aging Flashcards
Aging?
Represents a time-dependent decline in physiological function
Longevity and aging?
Distinct
Longevity - length of lifespan independent of aging
Damage theories?
Cumulative impact of assaults over the life course causes aging
Damage theory examples? We R ChieFS
Wear and tear theory
Rate of living theory
Cross-linking theory
Free-Radical theory
Somatic DNA damage theory
We R ChieFS
Wear and tear theory?
Over time the components of cells and tissues eventually wear out, leading to the aging of the organism
Rate of living theory?
An organisms rate of basal METABOLISM determines its lifespan - the higher the basal metabolism, the shorter the lifespan (eg rodents vs humans)
Cross-linking theory?
Accumulation of cross-linked proteins over time impairs cellular function, slowing down bodily processes and leading to aging
Free-Radical Theory?
Reactive oxygen species (ROS) cause damage to cellular macromolecules, (DNA, proteins) and organelles, impairing function. Accumulation of this damage over time results in aging
Somatic DNA damage theory?
Genetics MUTATIONS are acquired faster than they can be repaired. These accumulate over time leading to a breakdown of genetic integrity, resulting in aging
Program theories of aging?
Aging follows biological timetable - might be continuation of the growth and development programmes of fetal life and childhood
Program theories of aging examples?
Programmed longevity
Endocrine theory
Immunological theory
Programmed longevity?
this suggests that aging arises due to time-dependent changes in expression of key genes involved in growth or development.
Endocrine theory?
this suggests that hormonal influences (eg GH-IGFI signalling) constitutes a biological clock that determines the rate of aging of an organism
Immunological theory?
this suggests that progressive loss of immune system activity with increasing age leads to cellular stress and eventual death from impact of disease
Genomic hallmarks?
concern changes in gene, chromosome or genome structure or expression, changes in the epigenome, that result in cellular dysfunction, leading to aging.
3 genomic hallmarks?
- Genomic instability
- Epigenetic changes
- Telomere attrition
Genomic instability?
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
Epigenetic changes?
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
Transcriptional noise?
Inappropriate expression of genes
part of Epigenetic changes hallmark
Telomere attrition?
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
Cellular hallmarks?
Relate to changes in cell behaviour or function over lifecourse -> aging through failure to maintain or repair tissues or organs
Cellular hallmarks examples?
- Stem cell exhaustion
- Changes in cell signalling
- Cellular senscence
Stem cell exhaustion?
Decline in regenerative potential
Less cell division, less repair and maintenance of tissues, neoplasia formation
Changes in cell signalling?
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
Cellular senescence?
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
Biochemical hallmarks?
Relate to cellular changes in metabolism or biochemistry -> cell damage and dysfunction -> aging
Biochemical hallmarks examples?
- Impaired mitochondrial function
- Impaired proteostasis
- Impaired nutrient sensing
Impaired mitochondrial function?
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
Impaired proteostasis?
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)
Impaired nutrient sensing?
Mutations that impair function of activity of GH - IGF1 pathway = increased lifespan and healthy aging
However, very low GH-IGF1 signalling incompatible with life
