Biology of Ageing Flashcards
How is ageing distinct from longevity?
Aging is distinct from longevity, which is defined as the length of the lifespan independent of aging. This makes sense, as two individuals with similar lifespans are unlikely to ‘age’ at the same rate.
What are the two major groups of ageing theories that have emerged?
The damage theories of aging and the program theories of ageing
What does damage theories of ageing postulate?
Organisms experience environmental assaults throughout their lifespan. These insults can arise from external impacts (eg UV exposure), or from intrinsic physiological processes (eg Reactive Oxygen Species (ROS) generated from biochemical processes.
Damage (or error) theories of aging postulate that the cumulative impact of these assaults over the lifecourse causes aging.
What are examples of damage theories of ageing?
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.
What does program theories of ageing suggest?
Program theories of aging suggest that aging follows a biological timetable. This programme might be a continuation of the growth and development programmes of fetal life and childhood.
What are some examples of program theory of ageing?
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
Which theory of ageing is more generally widely accepted and has more evidence?
Damage theory
What are the criteria that hallmarks of ageing have to follow to be included?
(i) it should manifest during normal aging;
(ii) its experimental aggravation should accelerate aging; and
(iii) its experimental amelioration should retard the normal aging process and, hence, increase healthy lifespan
What are the genomic hallmarks?
Genomic instability , epigenetic changes, telomere attrition
How does genomic instability lead to ageing?
changes in the copy number and chromosome instabilbity are observed with increasing age and also changes to nuclear architecture and mitochondrial DNA which leads to cellular dysfunction leading to ageing
How does epigenetic changes lead to ageing?
Aging is associated with distinct epigenetic changes, including loss of DNA methylation, age-specific patterns of histone modification, and changes in the expression of enzymes that regulate DNA packaging and chromatin remodelling. Together, these lead to inappropriate expression of genes (transcriptional noise) and changes in the packaging and accessibility of DNA to proteins, which in turn can lead to impaired DNA repair and chromosome instability.
Hiw does telomere sttrition lead to ageing?
The ends of chromosomes contain repeated DNA sequences known as telomeres. In most cells, telomeres cannot be replicated fully by the DNA replication machinery, so shorten with each round of cell division, and once the telomere reaches a critical shortness, cells enter senescence (stop dividing).
Progressive loss of telomeres over the lifecourse of the organism is thought to lead to cellular senescence and an inability to maintain homeostasis in tissues, resulting in aging.
What are cellular hallmarks for ageing?
stem cell exhaustion, changes in cell signalling, cellular senescene
How does stem cell exhaustion lead to ageing?
Decline in the regenerative potential of tissues is a key hallmark of aging. Cell cycle activity in aged stem cells is reduced, leading them divide less frequently, and thus contribute less to repair and maintenance of tissues, resulting in aging.
How do changes in cell signalling lead to ageing?
Senescent cells (i.e. non-dividing cells at the end of their lifespan) can influence the cells around them to enter senescence too (so called bystander effect) through communication to neighbouring cells via gap junctions. Manipulation of signalling pathways, or prevention of chronic inflammation, may present attractive strategies for inhibiting aging.
