Biosystems II: Aging Lecture

How does basic metabolic rate relate to maximum lifespan and lifetime energy expenditure

-1 kg/mouse produce way more energy than 1 kg/elephant. -main reason, mouse has high surface to volume ration (will lose more heat, needs increased to maintain temp) -lifetime energy expenditure curve almost flat. Mouse produce more energy than elephant? -limit of lifespan depends on the size and metabolic activities. -if you slow down metabolism, may live longer

What is LaCroix's theory of aging? What factors contribute, what counteracts?

-aging is a way to avoid cancer RONS, ox stress, stem cell senescence/telomere erosion counteracted by apoptosis induction, enzymatic repair mechanism,scavenging by antiox

Telemere extension has what effect on aging?

-delays aging -no negative effect on mice. -embryonic stem cell from fertilized egg incubate (16 divisions)--> telomere become super long-->reimplant into unmodified embryo at blastula/morula stage-->gamete with long telomere. Animals are leaner (weighed less), less inflammation and healthier. Less cancer, live longer. +40% increase lifespan -tumor incidence

Mutations increasing lifespan:

100s of mutations that prolong life. Most mutations affect metabolism -one of the mutants was so you could not eat properly. Low metabolism. -the less you eat, the longer you live.

How is detoxification of mitochondria ROS accomplished? Where are these enzymes located?

Antioxidants from food Also: superoxide dismutase (SOD2 and SOD1 important: mutation is responsible for ALS/Leu Garig) superoxide anion + 2H+--.hydrogen peroxide Glutathione peroxidase: reduce hydrogen peroxide to water. (8 of these genes; GPX1-8) takes place in the intermembrane space and in the matrix.

Where is the source of electron leakage in the mitochondria? What is formed?

Complex I and complex III Superoxide anion is formed by partial reduction

Where does radical formation not occur in the mitochondria?

Complex IV bc no radical intermediates. Always 4 electrons and 4 protons to form water.

Production of ROS is used for what purpose in the immune system? What are formed? What enzymes catalyze this?

For imflammation.

In our own body, what are the immortal cells?

Germ cell line. Gotten from ancestors, given to offspring. -soma ages. Aging does not effect germ cells

What is the longest living vertebrate? How do they know the age?

Greenland shark-live up to 600 years. Cannot reproduce until 150 years. -living animal, can date when born (with carbon dating on a protein). Some proteins you get at birth and never replace for your whole life: proteins in the lance, never replaced. -lobsters dont age Species specific longevity in species or genes.

If a cell has high telomerase activity, it may be considered what?

Immortal. Bc it can rejuvenate the telomere and will prevent senescence. -Ex: cancer cells will express telomerase, stem cell. Drop in telomerase during fertilization. Blastula stage, telmorase starts to express again and sets the length of telomeres. Expression of telomerase in even stem cells is not long enough to prevent senescence forever. (do not have enough) Only embryonic stem cells have enough. and maybe cancer stem cells/cancer cells

Longevity limit: What causes people to think this is true?

Increasing maximum of older people until it plateaued in recent years.

What animals are immortal? What does that mean?

Jellyfish, Can still die, but do not age.

How does a macrophage attack bacterium?

Macrophage engulfs bacterium. NADPH willt ransfer electrons and partially reduce oxygen to create hydrogen peroxide and bleach, which attack the bacteria.

Production of the majority of ROS occurs where?

Mitochondria during ox phosphorylation (in the CAC/Krebs cycle) End product: water and o2

What are the 2 theories of aging? Weaknesses of each?

Programmed: -diversity allows species to adapt -need to get rid of the old -genetically programmed weakness: If the only function of a gene is to make you age and die, how can you pass this gene to kids (select the gene)? how do you use natural selection to select genes that make you unable to reproduce? Non-programmed: -aging is wear and tear -thermodynamic not efficient -not restricted to a finite number

What is an example of an animal that has the same genes but different lifespan?

Royal jelly for food, epigenetic changes, but the genes are the same. Queen lives 6 years, workers live 6 weeks.

What are some recent theories of aging correlation or causation? (3) -3 biologic parameters

Telemere length: counts rounds of cell division Endocrine: when you age, hormones reduce. Hormones themselves cause aging (but also might be effect) Epigenetic: in our DNA. Modification of DNA that affects gene expression. As we age, a lot of these expressions change. Not clear if cause or effect of aging.

What causes telomere shortening? What enyme fixes this?

The "end replication problem: DNA replicated from 5-->3. With antiparallel, can use an RNA primer. RNA primer degraded and replaced by DNA. In the end if you have an RNA primer that binds to the end, but no DNA to fill the gap. DNA gets a little shorter every time. Telomerase: can recognize the end (hanging strand). Binds and elongates the strand. Can extend the telomere. This enzyme is not present in all cells.

Telomere: where is it? what is the sequence? What is the maximum length? What is the main cause of stopped cell division?

The end of chromosome. TTAGGG sequence 5-15 Kb They get so short that they drive senescence and stop dividing. It is the main cause of stopped cell division.

Ames dwarf mice: What was the result of the experiment? How did they do it? What question was asked? What is healthspan?

do not produce growth hormone, so they are small, reduced growth. -these mice live much longer than normal. -less E production, less ATP, less free radicals Does CF and DF increase healthspan, lifespan or both? -healthspan starts from birth to the day where you see decline in a population. Extends healthspan, delays onset of disease and Also increases lifespan

Exogenous ROS production sources?

ex: acetaminophen -when metabolized, produce ROS

Is there a limit for maximum human lifespan? What does the survival plateau indicate?

largest increase in 40s thru 60s. Now plateau'd. Some think its a sign of a limit. ***improved medicine, but eat junk food. Maybe this is cause for plateau.