The age-associated changes of PARKIN

# # # #

Tiny variations in a region of DNA referred to as “Parkin” are associated with an increased risk of developing Parkinson’s (particularly young onset forms of the conditions). The Parkin DNA provide the instructions for making a protein that is involved with many functions inside cells.

New research indicates that as we age, Parkin protein becomes less available. In fact, by the time we turn 50 years of age, “Parkin is largely insoluble”, meaning that the majority of the protein is no longer able to do its job.

This shift appears to involve oxidation changes.

In today’s post, we will discuss what Parkin and oxidation are, how Parkin might be affected by oxidation, and how this information might be useful to treating Parkin-associated Parkinson’s.

# # # #


Me (I wish) before 27. Source: Pinterest

I don’t know about you, but 27 was my peak.

Before my 27th birthday, I could run around all over the place – acting like an idiot, with all the energy in the world. I was invincible and having lots of fun. And yes, some vices might have been involved – I would drink myself blind on a Friday night, wake up fresh the next day and do it all merrily again.

Me before 27. Source: Thefix

But then, my 27th birthday came along and I woke up the next day tired and feeling… fatigued. Weary even. And definitely with less enthusiasm than I had before I passed out the night before. My father called it a “hang-over” (which up until that time I had naively/idiotically thought I was immune to).

Me, before (left) and after 27 (right). Source: Wanna-joke

But I gradually developed this sinking feeling that it was something else.

Something more sinister.

It was as though something had changed. Something inside of me.

And I distinctly remember a moment of realisation, when I asked “Am I getting old???”

My father saw my concern and gave me sage advice (“It’s like I always say, aging ain’t for sissies“), and with that I changed my ways.

Source: DS

Since that moment, I have been fascinated by the biology of aging, particularly in the context of Parkinson’s (age is the main correlate with neurodegenerative conditions like Parkinson’s and Alzheimer’s). So it was with great interest that I read a manuscript in November last year that had been posted on the openly-available preprint database bioRxiv.

What did the manuscript say?

Continue reading “The age-associated changes of PARKIN”

I’m worried about my IMM-AGE

 

Researchers have recently described a new method to quantify a person’s “immune age” – a measure that could act as a key determinant of future health, as well as response to disease and treatment.

This novel test appears to provide a more reliable predictor for the status of one’s immune system than any other previous method.

And it could be useful in other ways.

In today’s post, we will discuss this new method of determining “immune age”, explore examples of how similar analysis has been used for other conditions, and consider what it could mean for Parkinson’s.

 


Source: Emaze

Do you remember Andre Agassi?

I know he’s still around, but when I was young and less beautiful, I was a big fan. Not only of his on court achievements, but also of his charismatic off-court image.

And it certainly paid off well for him:

One of the things that Agassi taught us was that “image is everything”.

Before Agassi, tennis was a conservative sport of white shirts & shorts (McEnroe was basically as radical as things got). It was bland, conservative, and – yes, I’ll say it – boring.

Agassi not only brought colour but charisma to the game. It was shocking and disgraceful to some, but to young, naive fools like me, it was a captivating breath of much needed fresh air.

Source: Hesaidandshesaid

Despite the early infatuation with the stylings of Mr Agassi, I have to admit that I have never remotely been concerned about own image. My dimensions mean that I wear what fits as opposed to what I like, and as a result the finished product is better behind a keyboard rather than speaking to a crowd.

But as I have gotten older, I have become concerned about a different kind of IMM-AGE (not a typo).

Let me explain: Recently some researchers in Israel and at Stanford University in the US published a rather remarkable research report which if replicated could have important implications for how we approach medical care.

What did they report?

Continue reading “I’m worried about my IMM-AGE”

Distinctly human?

 

It is often said that Parkinson’s is a ‘distinctly human’ condition. Researchers will write in their reports that other animals do not naturally develop the features of the condition, even at late stages of life.

But how true is this statement?

Recently, some research has been published which brings into question this idea.

In today’s post, we will review these new findings and discuss how they may provide us with a means of testing both novel disease modifying therapies AND our very notion of what Parkinson’s means.

 


Checking his Tinder account? Source: LSE

Deep philosphical question: What makes humans unique?

Seriously, what differentiates us from other members of the animal kingdom?

Some researchers suggest that our tendency to wear clothes is a uniquely human trait.

The clothes we wear make us distinct. Source: Si-ta

But this is certainly not specific to us. While humans dress up to ‘stand out’ in a crowd, there are many species of animals that dress up to hide themselves from both predator and prey.

A good example of this is the ‘decorator crab’ (Naxia tumida; common name Little seaweed crab). These creatures spend a great deal of time dressing up, by sticking stuff (think plants and even some sedentary animals) to their exoskeleton in order to better blend into their environment. Here is a good example:

Many different kinds of insects also dress themselves up, such as Chrysopidae larva:

Dressed for success. Source: Bogleech

In fact, for most of the examples that people propose for “human unique” traits (for example, syntax, art, empathy), mother nature provides many counters (Humpback whales, bower birds, chickens – respectively).

So why is it that we think Parkinson’s is any different?

Wait a minute. Are there other animals that get Parkinson’s?

Continue reading “Distinctly human?”

Sensing seriousness about senolytics

 

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 Rockefeller University suggests that these senescent cells could potentially explain certain aspects of Parkinson’s.

The good news 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:

Why do we hold on to stuff long after we don’t use it anymore?

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?

Continue reading “Sensing seriousness about senolytics”

Reduce your RAGE as you AGE

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 conditionsAGEs 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?

Continue reading “Reduce your RAGE as you AGE”