Researchers are building as ever increasing amount of evidence supporting the idea that as our bodies age, there is an accumulation of cells that cease to function normally. But rather than simply dying, these ‘non-functional’ cells shut down and enter a state which is refered to as ‘senescence‘.
And scientists have also discovered that these senescent cells are not completely dormant. They are still active, but their activity can be of a rather negative flavour. And new research from the
The good new is that a novel class of therapies are being developed to deal with senescent cells. These new drugs are called senolytics.
In today’s post, we will discuss what is meant by senescence, we will review the new data associated with Parkinson’s, and we will consider some of the interesting senolytic approaches that could be useful for PD.
This is not my living room… honest. Source: Youtube
Humans being are great collectors.
We may not all be hoarders – as in the image above – but everyone has extra baggage. Everybody has stuff they don’t need. And the ridiculous part of this equation is that some of that stuff is kept on despite the fact that it doesn’t even work properly any more.
The obvious question is:
Oh, and don’t get me wrong – I’m not talking about all that junk you have lying around in your house/shed.
No, I’m referring to all the senescent cells in your body.
Huh? What are senescent cells?
An Advanced Glycation Endproduct (or AGE) is a protein or lipid that has become glycated.
Glycation is a haphazard process that impairs the normal functioning of molecules. It occurs as a result of exposure to high amounts of sugar. These AGEs are present at above average levels in people with diabetes and various ageing-related disorders, including neurodegenerative conditions. AGEs have been shown to trigger signalling pathways within cells that are associated with both oxidative stress and inflammation, but also cell death.
RAGE (or receptor of AGEs) is a molecule in a cell membrane that becomes activated when it interacts with various AGEs. And this interaction mediates AGE-associated toxicity issues. Recently researchers found that that neurons carrying the Parkinson’s associated LRRK2 G2019S genetic variant are more sensitive to AGEs than neurons without the genetic variant.
In today’s post we will look at what AGE and RAGE are, review the new LRRK2 research, and discuss how blocking RAGE could represent a future therapeutic approach for treating Parkinson’s.
The wonder of ageing. Source: Club-cleo
NOTE: Be warned, the reading of this post may get a bit confusing. We are going to be discussing ageing (as in the body getting old) as well as AGEing (the haphazard process processing of glycation). For better clarification, lower caps ‘age’ will refer to getting old, while capitalised ‘AGE’ will deal with that glycation process. I hope this helps.
Ageing means different things to different people.
For some people ageing means more years to add to your life and less activity. For others it means more medication and less hair. More wrinkles and less independence; more arthritis and less dignity; More candles, and less respect from that unruly younger generation; More… what’s that word I’m thinking of? (forgetfulness)… and what were we actually talking about?
Wisdom is supposed to come with age, but as the comedian/entertainer George Carlin once said “Age is a hell of a price to pay for wisdom”. I have to say though, that if I had ever met Mr Carlin, I would have suggested to him that I’m feeling rather ripped off!
George Carlin. Source: Thethornycroftdiatribe
Whether we like it or not, from the moment you are born, ageing is an inevitable part of our life. But this has not stopped some adventurous scientific souls from trying to understand the process, and even try to alter it in an attempt to help humans live longer.
Regardless of whether you agree with the idea of humans living longer than their specified use-by-date, some of this ageing-related research could have tremendous benefits for neurodegenerative conditions, like Parkinson’s.
What do we know about the biology of ageing?