Biology of Aging Flashcards
What is aging?
- not clearly defined
- time-related deterioration of the physiological functions necessary for survival and reproduction
What is longevity?
The length of the lifespan independent of aging
What are damage theories of aging?
Aging is caused by the cumulative impact of environmental assualts over the lifecourse
What are some examples of damage theories?
- wear and tear theory
- rate of living theory
- cross-linking theory
- free-radical theory
- somatic DNA damage theory
What are program theories of aging?
Aging follows a biological timetable which may be a continuation of development programs of fetal life and childhood
What suggests that aging may be pre-programmed genetically?
- single-gene mutation disorders which have characteristics of accelerated aging
- e.g. Hutchinson-Guilford Progeria syndrome
What are some examples of program theories?
- programmed longevity
- endocrine theory
- immunological theory
Which theories of aging are more widely accepted?
Damage theories
What is meant by the term ‘Hallmarks of Aging’?
- common characteristics of aging across multiple species
- aims to identify biological pathways which contribute to aging
Which criteria must be met in order to qualify as a hallmark of aging?
- manifests during normal aging
- its experimental aggravation should accelerate aging
- its experimental removal should slow the normal aging process and therfore increase healthy lifespan
What are genomic hallmarks of aging
- hallmarks concered with changes in gene structure or expression
- genomic instability
- epigenetic changes
- telomere attrition
How does genomic instability lead to aging?
- 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
How do epigenetic changes lead to aging?
- 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
How does telomere attrition lead to aging?
- 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
What are the cellular hallmarks of aging?
- changes in cell behaviour or function over the lifecourse contributing to aging
- stem cell exhaustion
- changes in cell signalling
- cellular senescence?
What is stem cell exhaustion?
- stem cell function decreases with age
- less able to contribute to repair and maintaenance of tissues
- also accumulate mutatuions leading to neoplasia formation
How do changes in cell signalling lead to aging?
- more cells become senescent with aging
- senescent cells induce senescence in adjacent cells via cell signalling through gap junctions (bystander effect)
How does cellualr senescence contibute to aging?
- 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
What are the biochemical hallmarks of aging?
- changes in cellular metabolism or biochemistry which contribute to aging
- impaired mitochondrial function
- impaired proteostasis
- impaired nutrient sensing
How does impaired mitochondrial function contribute to aging?
- 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
How does impaired proteostasis contribute to aging?
- 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
What is the evidence for impaired nutrient sensing contributing to aging?
- impaired function in GH and IGF-1 increases lifespan and healthy aging
- dietary restrictions can extend lifespan
What is the information theory of aging?
Acquisitions of epimutations over the course of life leads to aging through the loss of youthful epigenetic information
What can be done to treat biological aging?
- targeting the hallmarks of aging
- stem-cell therapies
- anti-inflammatories
- elimination of damaged and senescent cells
- telomerase reactivation
- epigenetic drugs
- dietary restrictions
- mitochondrial treatments
