General Principles of Ageing Flashcards
What is health span?
the amount of time lived in healthy conditions
What is lifespan?
the total duration of an individual’s life, measured from birth to death
What is life expectancy?
the average number of years a newborn is expected to live if current mortality rates remain constant throughout their lifetime
What doe the geroscience hypothesis suggest?
the biological processes of ageing contribute to the development of diseases, and by slowing down or modifying the ageing process, it may be possible to delay or prevent the onset of multiple age-related diseases
What does the geroscience hypothesis work to do?
- advance the understanding of the biology of ageing
- identify novel therapeutics or lifestyle interventions to treat age-related diseases
- identify biomarker signatures of early dysfunction to maintain health
Give examples of non-modifiable and modifiable risk factors
- non-modifiable – genetics, age, family history, gender
- modifiable – diet, physical activity, alcohol use, smoking
What do evolutionary theories of ageing suggest?
ageing occurs because natural selection favours traits that enhance reproductive success early in life, rather than traits that promote longevity in later life
What are the 2 types of physiological theories of ageing?
programmed and damage/error theories
What are the 3 programmed theories of ageing?
- programmed longevity – consistently turning genes on/off leads to age-related aberrance and, when exhibited, a senescent phenotype
- endocrine theory – hormonal networks, such as the insulin-IGF1 signalling pathway, are used by biological clocks to set the rate of human ageing
- immunological theory – a dysfunctional immune system inspires pathogenic dominance and subsequent age-related decline of the vulnerable organism
What are the 5 damage/error theories of ageing?
- rate of living theory – as basal metabolic rate increases, life expectancy decreases
- free radicals theory – free radicals target vulnerable cellular macromolecules and render cells dysfunctional; endogenous antioxidants compensate to an extent but this threshold is passed in ageing
- wear and tear theory – essential and highly utilised cellular constituents wear with time, until they are no longer functional
- somatic DNA damage – rate of DNA damage accumulation surpasses the body’s natural compensatory capabilities; accumulation of genetic mutations and aberrance of mitochondrial DNA are also implicated
- cross linking theory – proteins undergo cross linking reactions and accumulate in this state within cells, damaging them and leading to ageing by retarding cellular function
What is a characteristic of many long-lived species?
better resistance to environmental stressors
What are the 3 criteria that must apply for each hallmark of ageing?
- the time-dependent manifestation of alterations accompanying the ageing process
- the possibility to accelerate ageing by experimentally accentuating the hallmark
- the opportunity to decelerate, halt, or reverse aging by therapeutic interventions on the hallmark
What do primary hallmarks of ageing do?
progressively accumulate with time and unambiguously contribute to the
ageing process
What do antagonistic hallmarks of ageing do?
reflect responses to damage
What are integrative hallmarks of ageing?
the accumulated damage inflicted by the primary and antagonistic hallmarks and cannot be compensated anymore
What do integrative hallmarks of ageing result in?
- stem cell exhaustion
- intercellular communication alterations including extra cellular matrix (ECM) damage
- chronic inflammation and dysbiosis
What are the 4 primary hallmarks of ageing?
- genomic instability
- epigenetic modifications
- telomere attrition
- proteostasis
What is genetic instability?
the accumulation of genetic mutations, chromosomal damage, and DNA degradation over time; it accelerates the ageing process and heightens the risk of diseases
What can epigenetic modifications do?
affect specific genes or transcriptional programmes which are important for ageing, survival, cellular growth and senescence or death
Give examples of epigenetic modifications
- DNA methylation
- histone modification
- chromatin remodelling
What are telomeres?
protective caps at the ends of chromosomes that shorten with each cell division
What is telomere attrition?
when telomeres shorten over time and trigger cellular senescence, which contributes to tissue ageing and a decline in tissue regeneration
What is proteostasis?
the balance of protein synthesis, folding, and degradation within a cell
What is the result of a collapse in proteostasis?
accumulation of damaged/misfolded proteins that can cause cellular stress, impair normal cell function, and promote the formation of protein aggregates; cell function is impaired and ageing is accelerated
