Paper(s): Baker, D., Wijshake, T., Tchkonia, T. et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479, 232–236 (2011). https://doi.org/10.1038/nature10600. This was the paper that launched Unity Biotechnology. Later shown in WT mice Baker, D., Childs, B., Durik, M. et al. Naturally occurring p16Ink4a-positive cells shorten healthy lifespan. Nature 530, 184–189 (2016). https://doi.org/10.1038/nature16932.
Presented by Tara Mei on 3/27/2022
Senecent Cells and Aging
What is a senescent cell?
Image: NIA
SASPS
Image: Roe Ethridge
The GOOD
Tumour suppression
Embryonic development
Wound healing
The BAD
Tumour growth
Seem to be present in lots of aging diseases
?
?
QUESTION
What happens if you remove senescent cells?
BIGGER QUESTION
Are senescent cells causal in aging diseases?
STEP 1: Made a transgene that removes SCs in mice upon drug treatment
STEP 2: Cleared SCs with drug
STEP 3: Checked for effects of clearing SCs on aging
So what happened?
Delayed lordokyphosis
Delayed cataracts
Larger muscle fibres
Larger fat deposits
Better exercise
So what happened?
…but no lifespan increase
Side effects: None
Delayed lordokyphosis
Delayed cataracts
Larger muscle fibres
Larger fat deposits
Better exercise
What happens if you remove SCs later in life?
Not mentioned
QUESTION
What happens if you remove senescent cells?
BIGGER QUESTION
Are senescent cells causal in aging diseases?
So what happened?
Lifespan increase
Delayed cataracts
Larger fat deposits
Reduced glomerulosclerosis
Increased cardiac stress tolerance
Side effects: Slower wound closure
New!
New!
n=14
n=9
Still unclear:
Do both chronic and acute senescense matter in aging disease?
Why do senescent cells accumulate with age?
What might side effects of clearing SCs be?
Are all cell types equally responsive to senolytics?
How do we characterise senescence/how many markers are enough?
senescence-associated β-galactosidase
enlarged cytoplasm
lack of DNA replication
expression of kinase inhibitors p21 and p16
nuclear senescence-associated heterochromatin foci
SASPS