The Molecular Basis of Aging & Disease Flashcards
Define longevity
How long an organism lives
Define senescence
Time related deterioration
Define mortality rate
The probability of death in a given period of time
What is semelparity?
Genetically programmed senility and death after reproduction
Name a species which undergoes semelparity
Pacific salmon
What are the four distinct mortality phases in humans?
1) Raised mortality in infancy
2) low mortality until midlife (~60 years)
3) high mortality from midlife to old age
4) Reduced mortality in extreme old age
Name two ways to find out which genes protect/ promote aging, death and damage in life?
Genetic linkage studies and genome wide association studies
What kind of diseases of premature aging can be found using genetic linkage studies?
Monogenic, causal
What kind of diseases can be found using GWAS?
Complex with many SNPs and low effect size
What are progeroid syndromes?
A group of genetic disorders characterised by clinical features mimicking physiological ageing at an early age
True or false: Progeroid syndromes are monogenetic?
True
What is segmental progeria?
A progeroid disease affecting multiple tissues. It is autosomal recessive.
An example is Werner Syndrome (gene: WRN)
What is unimodal progeria?
A progeroid disease which affects one main tissue. It is autosomal dominant. An example is familial Alzheimer’s disease (gene: APP)
What is the most common feature of accelerated aging in progeroid syndromes?
A loss of genome integrity
What do progeroid syndromes tell us?
There are similarities between the molecular hallmarks of aging and human progeroid symptoms. There is a powerful argument that molecular defects which cause these syndromes are the major causative agents of agent.
What are the primary hallmarks of aging (causes of damage)?
Genomic instability, telomere attrition, epigenetic alterations and loss of proteostasis
What are the antagonistic hallmarks of aging (responses to damage)?
Deregulated nutrient sensing, mitochondrial dysfunction and cellular senescence
What are the integrative hallmarks of aging (culprits of the phenotype)?
Stem cell exhaustion and altered intercellular communication
