Introduction to Aging Flashcards
What is the mutation accumulation theory of aging?
Because of extrinsic mortality and rarity of aged animals in a natural pop, the force of selection is too weak to oppose the accum of germline mutations with late-acting deleterious effects. “Aging is a matter of neglect”
What is the disposal soma theory of aging?
Aging is the result of the accum of dmg, which can be repaired at the expense of repro effort. Lifespan is determined by the balance of resources invested in longevity vs repro fitness.
“Aging is a matter of resource allocation”
What is the antagonistic pleiotropy theory of aging?
Some genes may be selected for beneficial fx on repro and survival successes early in life, but the same genes have unselected deleterious fx with age, which contributes directly to aging. Longevity is therefore antagonistic to repro and survival fitness.
“Aging is a reflection of imperfections”
Example: bone calcification in young is good, bad in old for arteries.
Name as many cellular and molecular hallmarks that appear in aged tissues.
Genome instability, telomere attrition, epigenetic alterations, proteostatic stress, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, & altered intercellular accumulation.
Aging results from a decline in the force of [blank] acting on traits in late life.
Natural selection
Explain the naked mole rat success story
Less predation leads to less pressure for successful reproduction leads to an extended lifespan because there are more resources for cell maintenance.
The Free Radical (oxidative stress) Theory of Aging
Aging is an accum of oxid dmg to biomolecules as well as mitochondria (which produce more ROS).
However, studies haven’t shown correlation betw free radical production and shortened lifespan.
Mitochondrial dysfunction may cause aging in a manner
dependent or independent of ATP and ROS production. How so? Just look at the answer it’s a long ass list.
They function in metabolism & cell growth; synthesis of pyrimidine, iron-sulfur cluster, heme, aa’s, phospholipids; heat, work, protein homeostasis, ROS signaling, and apoptosis. We need to figure out if free radical production has an effect on cell function.
Cell Senescence/Telomere Shortening theory of aging
I’m not gonna describe it, it’s pretty self-explanatory. Know that it has its caveats as a theory.
Somatic Mutation Theory of Aging
DNA dmg followed by DNA repair, but in the process of replication, mutations, rep errors, genomic instability, and persistent DNA dmg lead to either aging or cancer.
The Proteostatic Stress Theory of Aging (the most popular molecular theory for aging)
The loss of protein homeostasis whereby they become damaged, misfolded, aggregated and become toxic. It induced apoptosis which leads to aging.
Why have dwarf mice been shown to live at least 50% longer than normals?
Dwarf mice are defective in GH production or function.
Reduced IGF-1/Insulin signaling extends lifespan. How?
FOXO no longer inhibited by Akt/PI3 Kinase ptwy. FOXO benefits survival and inhbits aging. mTOR (pro-aging) no longer activated.
How does activation of FOXO txnl factor benefit survival?
Target genes influence ROS detox, cell cycle arrest, DNA repair, glucose metab, & energy homeostasis.
Basically, it increases cellular maintenance, stress resistance, & metabolic homeostasis.
Reduced mTOR signaling favors cell survival. How?
mTOR senses nutrient abundance and inflammation; it’s a key regulator of increasing cell growth. Downregulating it decreases cell growth and increases the resources for cell maintenance and repair.
