Senescence-associated secretory phenotype (SASP) and theophylline

#1

A study showing that theophylline reduces the number of senescence-associated secretory phenotype (SASP). If so, could theophylline, along with senolytics, further increase the number of senescent cells and benefit longevity?

https://avesis.gazi.edu.tr/yayin/f1219d10-a9d1-4604-9805-fa6da9109324/a-potential-senotherapeutic-drug-theophylline-restores-the-doxorubicin-induced-senescent-cell-morphology-in-a549-cells

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#2

Interesting…

Performance enhancement in sports

Theophylline and other methylxanthines are often used for their performance-enhancing effects in sports, as these drugs increase alertness, bronchodilation, and increase the rate and force of heart contraction.[9] There is conflicting information about the value of theophylline and other methylxanthines as prophylaxis against exercise-induced asthma.[10]

Adverse effects

The use of theophylline is complicated by its interaction with various drugs and by the fact that it has a narrow therapeutic window (<20 mcg/mL).[2] Its use must be monitored by direct measurement of serum theophylline levels to avoid toxicity. It can also cause nausea, diarrhea, increase in heart rate, abnormal heart rhythms, and CNS excitation (headaches, insomnia, irritability, dizziness and lightheadedness).[2][11] Seizures can also occur in severe cases of toxicity, and are considered to be a neurological emergency.[2]

Its toxicity is increased by erythromycin, cimetidine, and fluoroquinolones, such as ciprofloxacin. Some lipid-based formulations of theophylline can result in toxic theophylline levels when taken with fatty meals, an effect called dose dumping, but this does not occur with most formulations of theophylline.[12] Theophylline toxicity can be treated with beta blockers. In addition to seizures, tachyarrhythmias are a major concern.[13] Theophylline should not be used in combination with the SSRIfluvoxamine.[14][15]

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#3

IMO it’s likely the best of the methylxanthines for aging, far better than caffeine, but we don’t have direct evidence one way or the other. All drugs in this class will have dosage limited by toxicity.

#4

I don’t think you really want to increase the number of senescent cells :slight_smile:

The best way to reduce SASP is to clear out senescent cells as they are the sole source of SASP. Fewer senescent cells = lower SASP