Treating Old Cells: Progress In Reducing Chronic Inflammation

Acute inflammation Credit: Department of Pathology, Calicut Medical college

Inflammation is a big player in many aging processes, from arthritis to facilitating cancer and even increased telomere shortening. We need to find ways to reduce its burden, and research is beginning to offer solutions.   

What is inflammation?

It's a popular word nowadays, but many people don't really know what is it. Inflammation is a response to damage, but essentially a faulty, or over-exaggerated response to it. Your body has to make decisions every time a cell is damaged or a pathogen invades you and this effects how much 'collateral' damage is inflicted on neighbouring tissue. The problem is that inflammation is a complex balancing act, and one the body loses control over as you age. One one hand, if you have insufficient inflammation you'll be easier to dispatch by disease and won't eradicate damage effectively, but if you have too much? You damage your own body and cause lots of other problems at the same time.  

Senescence gives rise to inflammation

Humans are comparatively fairly good at holding off cancer, and one of the mechanisms we think helps stave it off is senescence. When cells become damaged, they can either be killed off, survive and risk going cancerous, or become senescent. This means they stop dividing and hang around spewing out signals. This mechanism may help stop cancer developing in youth by placing at risk cells in stasis, but senescent cells linger around for a long time; releasing a cocktail of inflammatory molecules called the SASP (senescence-associated secretory phenotype). Senescence also occurs after a cell has divided a certain amount of times and its telomeres are worn down - unless it's been 'immortalised' like in cancer cells. Certain cell types like stem cells can also divide many more times.

Senescent cells have a distinctive appearance

There are lots of theories about why we have senescence at all, and many people believe that while it may help an organism stay healthy in youth, it has consequences that arise later on. This ties in with the evolutionary theory of aging, in which certain aging processes have been favoured. 

What can we do about it?

At a minor level there are anti-inflammatory foods and medications like aspirin and ibuprofen that can reduce the burden slightly. These are currently not licensed for long-term treatment of age-related inflammation however and only ameliorate the problems. 

Most inflammation arises from senescent cells, and they're a big anti-aging target. There are a number of solutions people have discussed, from removing them altogether to lengthening telomeres. When mice were engineered so that senescent cells were quickly removed, they experienced a 20-25% increase in lifespan. New research is also focusing on reducing the inflammatory signals they release.  

Chronic inflammation leads to age-related frailty

Calming the body down

Recent research has uncovered that inhibiting a family of enzymes called the Janus Kinase family (JAK) can reduce the factors released by senescent cells - calming their harmful behaviour. Interestingly, there's hope that inhibiting these same enzymes can restore hair growth

When the research team analysed old mice treated with these inhibiting drugs, the animals showed improvements in grip strength, endurance and physical activity. They also exhibited fewer inflammatory markers. It's may not be a cure-all, but it could be quickly implemented given that these drugs are already approved for other conditions.

"One of the things we want to do is find some kind of treatment for this other than prescribing better wheelchairs or walkers, or other kinds of things that we are stuck with now that are Band-Aid solutions"

Other potential treatments

'Anti-aging' drug rapamycin has also been studied for its inflammation busting capabilities (among other benefits). It was able to prevent tumours from relapsing due to harmful inflammation, and showed potential in reducing overall inflammation when dosed intermittently. It's a potent and potentially harmful drug, but there's hope that in small bursts it could have positive effects. We'll have to wait for more research to find out more.

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