Life Changing:

.title[
# Life Changing:
]
.subtitle[
## Genetics and Treatments of Ageing
]
.author[
### Rebekah J White
]
.institute[
### University of Exeter & The Royal Society
]
.date[
### EMPSEB 30 April, 2022
]

---

# Why do we need lifespan and healthspan altering drugs?

<img src = "https://i.pinimg.com/originals/70/63/62/706362c3d7c74fb0425b4d6a865db73e.gif" />"

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# Why do we need lifespan and healthspan altering drugs?
## In general -
Increase lifespan: Aid in targeting age-linked decline in humans 
No change in lifespan: Safe to use / less likely to have confounding factors 
Decrease lifespan: Pests/parasites, or know to avoid

So, all results are useful.

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# How do we get started?

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### How do we get started?

* Not starting in humans 
 * Risky, time consuming, expensive, unethical, overall difficult 
--

* Therefore, start in the lab 
 * Cells or tissue in a dish is useful but ex situ studies have issues, e.g., not considering systems biology... so use a model

* Need a model that fits certain criteria 
 * Lab tractable, inexpensive, short lifespan, and more

---

.center[
![C. elegans](https://c.tenor.com/F3F7xNG27P8AAAAC/omw-worm.gif)]
#.center[Nematodes are a good fit]

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# Next, you need a drug that may change lifespan/healthspan...

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# Finding a drug

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# P. pacificus nematodes + nystatin

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<video loop autoplay controls width="100%" height="100%" controls id="my_video">
 <source src="pfiss_snuffle_Trim.mp4" type="video/mp4">
</video>]

<img src = "https://upload.wikimedia.org/wikipedia/commons/thumb/9/95/Nystatin.svg/800px-Nystatin.svg.png" /> ]

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# We also need an indicator of healthspan 
## Rupturing

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## Lifespan assay
#### General method

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## Lifespan assay
#### General method

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# Nystatin shortens lifespan (p < 0.05)

![](nys123 .jpg)

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# ... and healthspan (p < 0.05)

--
![](nys123rup.jpg)

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# Great - so something happens here
## But we can learn even more
How does gene expression change with the drug?

Knowing this will allow
* Gene targets
* Increased translatability to other organisms 
* Relevance as a anti-parasitic drug

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#RNAseq

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# Differentially expressed genes with nystatin

Some differences in upregulation (left) and downregulation (right):

* Gene

* Gene
]

* Gene

* Gene
]

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# What do these genes do?

If you want to generate a table, make sure it is in the HTML format (instead of Markdown or other formats), e.g.,

```r
knitr::kable(head(iris), format = 'html')
```

<table>
 <thead>
 <tr>
 <th style="text-align:right;"> Sepal.Length </th>
 <th style="text-align:right;"> Sepal.Width </th>
 <th style="text-align:right;"> Petal.Length </th>
 <th style="text-align:right;"> Petal.Width </th>
 <th style="text-align:left;"> Species </th>
 </tr>
 </thead>
<tbody>
 <tr>
 <td style="text-align:right;"> 5.1 </td>
 <td style="text-align:right;"> 3.5 </td>
 <td style="text-align:right;"> 1.4 </td>
 <td style="text-align:right;"> 0.2 </td>
 <td style="text-align:left;"> setosa </td>
 </tr>
 <tr>
 <td style="text-align:right;"> 4.9 </td>
 <td style="text-align:right;"> 3.0 </td>
 <td style="text-align:right;"> 1.4 </td>
 <td style="text-align:right;"> 0.2 </td>
 <td style="text-align:left;"> setosa </td>
 </tr>
 <tr>
 <td style="text-align:right;"> 4.7 </td>
 <td style="text-align:right;"> 3.2 </td>
 <td style="text-align:right;"> 1.3 </td>
 <td style="text-align:right;"> 0.2 </td>
 <td style="text-align:left;"> setosa </td>
 </tr>
 <tr>
 <td style="text-align:right;"> 4.6 </td>
 <td style="text-align:right;"> 3.1 </td>
 <td style="text-align:right;"> 1.5 </td>
 <td style="text-align:right;"> 0.2 </td>
 <td style="text-align:left;"> setosa </td>
 </tr>
 <tr>
 <td style="text-align:right;"> 5.0 </td>
 <td style="text-align:right;"> 3.6 </td>
 <td style="text-align:right;"> 1.4 </td>
 <td style="text-align:right;"> 0.2 </td>
 <td style="text-align:left;"> setosa </td>
 </tr>
 <tr>
 <td style="text-align:right;"> 5.4 </td>
 <td style="text-align:right;"> 3.9 </td>
 <td style="text-align:right;"> 1.7 </td>
 <td style="text-align:right;"> 0.4 </td>
 <td style="text-align:left;"> setosa </td>
 </tr>
</tbody>
</table>

---

# What do we now know?

* Nystatin decreases lifespan 
* This is likley due to upregulation of so and so genes and downregulation of so and so genes 
* These genes are putatively involved in lifespan regulation and prevention of rupturing 
* Worm knock-outs/knockdowns of these genes? 
* Next this will be examined in further nematode species in the lab to elucidate effected genes and pathways to increase translatability to other families, such as parasitic nematodes 
* This provides insight into the evolution of lifespan and age-linked decline

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##I am following this process in 8 other treatments and in three species of Pristionchus nematodes,
##and imaging the worms after exposure...

##So watch this space!

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# Thank you to

![](rslogo.jpg)

]

.pull-right[
Twitter [**@rebekah_jwhite**](https://twitter.com/rebekah_jwhite) 
GitHub [**berk1835**](https://github.com/berk1835)

Slides created in RStudio via the R package [**xaringan**](https://github.com/yihui/xaringan).

<img src="uoelogo.png" width="6667" />
]