LongeCity - Aging Science

6 question for the dedicated biogerontologist. If you can answer them correctly it indicates you have a good knowledge on very relevant areas in current research, enjoy!

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Nuclear reprogramming factors are used to make cells “younger”. Which factors are used and which methods have been used to quantify the success of this technique?
CRISPR-Cas9 to insert a flP cassette, improved autophagy in the cells which was measured by increased protein leakage. After treatment the mice did better on a Morris-Maze water test and appeared happy with high energy levels.
Clears protein and lipid garbage (lipofuscin) which enables the nucleus in the cell to regenerate and express more RAN-GTP. It then becomes more responsive to factors wanting to be imported into it which creates an anti aging effect.
The transcription factor genes KLF4, OCT4, NANOG, c-MYC, LIN28, and SOX2 which are also named Yamanaka factors. They measured a reduction of inflammation, improved regenerative response in muscle stem cells, changes towards a more youthful methylation pattern in an epigenetic clock.
An approach in bioinformatics to model the nucleus using different codes that simulates the degeneration of the nucleus with age. When testing that simulation one can see what actually works to produce results that can be applied in vitro later. Nuclear reprogramming can be done in a variety of programming languages such as Python, R and Tensorflow.
Implantation of an artificial cell nucleus made of titanium that rejects misfolded protein cargos, this could be used to slow down aging and are tested in tissue samples of children with Hutchinson-Gilford progeria.

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What are common markers to quantify cellular senescence in tissues? What are advantages and disadvantages?
P53 is the master regulator gene that is normally used as a marker, if it is inhibited the cell turns senescent. It can be discovered through a variety of techniques such as western blotting and ELISA which are cheap for biotech companies.
Labelling them with a fluorescent protein such as GFP with a “senescent tag”. Senescent cells do not divide and if isolated in a petri dish they appear dull and inert but can shine bright if taking up Senescent-associated Beta-Galactosidase.
A RNA-based expression technique such as RNA-seq.
In aged laboratory animals one can measure an increase in SASP through whole-body tissue homogenization. Interleukin-1 is normally heavily increased.
Cyclin-dependent Kinase inhibitors such as p21 and p16. There is no agreed universal marker for all types of senescent cells and there is a significant heterogeneity between tissues.

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What putative benefits can be concluded from using HDAC inhibitors as drug candidates for aging?
There is an increased level of HDAC activity in aged cells. Oxidative stress, inflammation and mitochondrial function is improved when it is inhibited due to enhancement of cellular stress response.
Increased NAD activity in oxidative phosphorylation.
HDAC reverses histone deacetylation which makes the histones bind around DNA more tightly. A tightly bound DNA is prevalent in youth but loosens up with age and becomes disorganized and subsequently affects aging positively.
The glycolysis progresses more rapidly in old organisms which emulates the young. This occurs due to a stress response when the cell is deprived of Hexokinase, Deoxyribose, Alanine and Cytosine (HDAC).
Thicker composition of cellular membranes due to more youthful levels of membrane lipids.

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What would be expected to cause the improvements observed in young-old haematopoetic stem cell transplants in mice?
More viscous blood leading to less atherosclerosis with age.
Better immune function caused by the CD4 and CD8 immune cells, this would affect the body systemically with increased amounts of LSK cells. Lifespan was also increased by 12% in these stem cell transplant experiments
Reversal of fibrosis due to less growth factors, this delays systemic tissue aging and studies have extended lifespans of mice with up to 27% from this
Stem cell therapies will give systemic effects since transplanting one type of stem cell in the blood will activate all types of stem cells in different tissues.
More active removal of accumulated toxins through better filtration rates in kidneys.

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Which of the following mechanisms has been linked to loss of melanocyte stem cells?
The circadian clock in the body cells has a preprogrammed rate of when to turn hair grey through the Cry and Per proteins, uneven sleeping patterns and night shifts therefore cause more rapid greying of hair due to dysfunctional stem cells.
Stem cells can be lost through repetitive cleansing with Shampoos since many contain low grade cytotoxic agents. Through replacing Shampoos with natural alternatives such as coconut oil one can expect a reduction in the rate of hair graying
Noradrenaline depletes melanocyte stem cells during stress which causes permanent greying.
Excessive body fat causes premature greying of hair since adipocytes are toxic to melanocyte stem cells. This is why calorie restricted mice go gray later.
Greying of hair is associated with too much metal consumption in the diet which stains the stem cells and subsequently produces grey hair.

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Of the following proteins, which is linked to cellular aging and how?
MreB protein causes the cells to grow too big and become unable to support their cytoskeletal structure.
Retinoic acid binding protein, the main cause of wrinkles is that it stops binding retinoic acid which degrades the extracellular matrix.
Rhodopsin, it accumulates in the eye and contribute to agerelated macular degeneration
BCL-xL, this is a mitochondrial protein controlling cellular senescence
Hydrolases, they become overexpressed and cleave apart many cellular structures which causes the inside of cells in an aged organism to become a slur that cannot perform basic functions.

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