Lecture 17

What are the primary hallmarks of cellular damage associated with aging?

Specific alterations to DNA and protein in the cell, Genetic instability, Loss of telomeres, Epigenetic alterations, Loss of proteostasis

What are the major sources of DNA damage?

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* Exogenous sources: chemical and biological agents
* Endogenous sources: DNA replication errors, spontaneous hydrolytic reactions, reactive oxygen species (ROS)

What are the repair mechanisms associated with aging?

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* Repair to DNA
* Repair to accelerated loss of telomeres
* Integrity of mitochondrial DNA (mtDNA)

How does UV light contribute to DNA damage?

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* UV light can cause adduct formations, which are difficult to repair.
* It can lead to double strand breaks and base damages.

What is the significance of telomere shortening in chromosome aging?

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* Telomere shortening is associated with aging.
* Repairing and extending telomeres can have anti-aging effects.
* Telomerase is considered anti-aging.

What are telomeres?

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* Telomeres are repetitive sequences at the end of chromosomes.
* They are typically around 10 to 15 kilobases in length but get trimmed after every cell division.
* Once telomeres reach a certain short length, cell division stops, leading to aging.

What are the three main causes of epigenetic traits?

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* DNA and histone methylation patterns
* Acetylation of histones
* Chromatin remodeling

How do methylation and acetylation affect gene expression?

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* Methylation and acetylation influence the structure of DNA and histones.
* DNA methylation and histone acetylation can make genes more or less accessible to transcription factors.

How are epigenetic marks inherited?

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* DNA methylation patterns can be inherited by daughter cells.
* The environmental history of the mother can be passed down to the next generation.

How can unfolded proteins contribute to the aging phenotype?

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* Heat shock, ER stress, and oxidative stress can unfold normally folded proteins.
* Unfolded proteins can aggregate, leading to the aging phenotype.

What is deregulating nutrient sensing associated with aging?

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* Deregulation of nutrient sensing, including growth hormones and insulin-like growth factor (IGF-1), is associated with aging.
* Declining IGF-1 levels and less efficient insulin responses are responses to aging.

What is cellular senescence?

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* Cellular senescence is the process by which the capacity for cell division, growth, and function is lost over time.
* Accumulation of senescent cells reduces tissue functions.

How does stem cell exhaustion contribute to aging?

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* Stem cell exhaustion occurs when stem cells are lost, leading to reduced tissue function.
* Rejuvenation of stem cell population through induced pluripotent stem cells can have anti-aging effects.

How does obesity impact aging?

* Obesity accelerates aging.
* Obese individuals may have damaged DNA and shorter telomeres.
* Olive oil and increased intake of broccoli can potentially increase lifespan.

How does Nrf2 play a role in antioxidant activity?

* Nrf2 is targeted to the proteasome by Keap1.
* Oxidative stress can stimulate Keap1 to release Nrf2, allowing it to enter the nucleus and stimulate the expression of antioxidant enzymes.
* Sulforaphane in broccoli can bind to Keap2, inhibiting proteasome targeting and resulting in increased antioxidant activity.