Flashcards in Intro to Aging Deck (19):
What are biomarkers used for aging? What does the Gompertz law state?
Death rate and lifespan (ie chronological age); death rate increases exponentially with age in protected environment where external causes of death are negligible, but prob of dying in a give year doubles every 8 years
What is life expectancy? What factors does this reflect?
Average # of years of life remaining at a given age;
econ status, childhood death, infectious diseases, biological aging, levels of health care, etc.
What are the four theorys of aging?
1. Programmed theory of aging - evolution selected genes that promote aging in order to limit pop size or accelerate generation turnover, but under serious challenge
2. Mutation accumulation theory of aging - aging is a matter of neglect, and force of selection cannot oppose accumulation of alleles with late deleterious effects over generations; if we don't die off, like in a protected environment, we deal with cataracts, osteoporosis, etc.
3. Antagonistic pleiotropy theory of aging - some genes may be selected for beneficial effects on repro and survival successes early in life, but same genes have unselected deleterious effects with age --> aging; look at mole rat that has less selection on repro, but has extended life span since deleterious gene effects are postponed
4. Disposal soma theory of aging: successful repro and progeny limit time allocated to damage repair at cellular level (longevity at cost of repro fitness)
What is the greatest risk of diseases? What is compression morbidity? If we treat people with early onset degen diseases, what could that allow for with patients?
Aging; thought that slowing down aging process might delay onset of aging-related degen disorders;
extended lifespan and healthspan (latter is length of time when one is in "optimal" health)
What are hallmarks in aged tissues (9)?
Genome instability, telomere attrition, epigenetic alterations, proteostatic stress, deregulated nutrient sensing, mito dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication
What does the free rad (oxidative stress) theory of aging include? What opposes this hypothesis?
Hydroxyl radical can damage cellular components and lead to aging, like the mito, leading to more ROS and more mito deterioration;
In mice, heterozygosity of Sod2 (Mn-Sod) leads to more 8-deoxyguanosine accumulation and increased tumor incidence, but NO SHORTENED LIFESPAN
What is the mito theory of aging?
Dysfunctional mito could contribute to aging by affecting energy depletion, more apoptosis and necrosis, nuclear genome instability, problems with redox balance, and global protein homeostasis issues
What does the cell senescence/telomere theory of aging include? What contradicts this theory?
Replicative cellular senescence contributes to aging, consistent with antagonistic pleotropy theroy of aging such that cell senescence early can suppress cancer early but later on could cause frailty; naked mole rat can live a long time even though its telomere length is shorter than a rodent, which has a shorter lifespan
What does the somatic mutation theory of aging predict?
DNA damage is the primary cause of aging, leading to replicative errors, mutations, persistent DNA damage, and genomic instability
What is the proteostatic Stress Theory of Aging talking about?
Protein dysfunction, disruption of cell membranes, formation of toxic protein aggregates, and apoptotic or non apoptotic cell death
Of the Ames and Snell mice, which lived longer? What cascade would normally be triggered with GH?
Dwarf mice defective in GH or GH receptor knocked out;
GH --> IGF-1 --> PI3 Kinase --> Akt --> mTor --> Aging; Akt inhibits FOXO, which would otherwise prevent aging
When FOXO is upregulated, what happens? If you downregulate mTOR, what happens to a cell? What can downregulate mTOR as a drug? What upregulates mTOR and what downregulates it?
Cell maintenance, stress resistance, and metabolic homeostasis;
decreased cell growth and increased cell maintenance and repair;
Aa's, inflammation, insulin/IGF-1 upreg, low energy/AMPK and stresses downregulate
In Laron syndrome, what do patients end up having?
Free of cancer and with low blood insulin levels, as well as higher insulin sensitivity levels; however, they don't have longer lifespans and can actually suffer from obesity
How much of longevity is attributable to heriditary factors? When do you feel impact of genetic factors?
25%; past the age of 60
What genes have been found to be associated with longevity?
FOXO3A (controls growth, metabolism, stress resistance), CETP (transport of cholesteryl esters and triglycerides between lipoproteins), APOC3 (component of VLDL that inhibits LPL), TOMM40 (encodes protein translocase on mito outer membrane)
What is associated with Hutchinson Gilford Progeria Syndrome? What is it a member of in terms of syndromes?
Elevated DNA damage, epigenetic alterations, chronic p53 signaling, inflammation, metabolic alterations, autophagy deregulation, stem cell dysfunction, protein dyshomeostasis; segmental progeroid syndromes (could show cardiovascular aging but no neurodegeneration and cancer)
How can caloric/dietary restriction help increase max lifespan?
Activating FOXO TF (increase stress resistance), reduce mTOR signaling (decrease protein translation), activate AMPK and AMP to remodel metabolism, and increase autophagy; also decrease insulin/IGF-1
What can exercise help do at molecular level?
Increased ATP synthesis and O2 consumption, increased hormetic response and stress signaling, increased mito density and metabolic capacity and resistance to oxidative stress, and then increased bioenergetic reserve, these latter two inhibiting aging process