Longevity Briefs: Can High Intensity Exercise Help Eliminate ‘Zombie Cells’?

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

Ageing is accompanied by cellular senescence, where cells become unable to divide but also refuse to die. These ‘zombie cells’ accumulate and release inflammatory signals and other harmful molecules, leading to tissue dysfunction and diseases. Previous studies have suggested that exercise, and especially high intensity exercise, leads to a reduction in senescent cell burden in various tissues and organs. Why? One theory is that exercise-induced muscle damage activates a brief inflammatory immune response, which boosts the clearance of senescent cells. In this study, researchers set out to test this theory.

The discovery:

12 men aged 20–26 underwent a short bout of high-intensity interval exercise (HIIE) consisting of 15 sets of 20-second cycling. Researchers took muscle biopsies before and after exercise, and measured expression of  p16INK4a mRNA, a marker of cellular senescence. As expected, HIIE was associated with a reduction in p16INK4a, but here’s where it gets interesting: participants had been randomly assigned to take the anti-inflammatory medication ibuprofen or a placebo before undergoing exercise. The study found that 3 hours post-exercise, p16INK4a levels were reduced to 20% of their pre-exercise levels in the placebo group, but only to 50% in the ibuprofen group. In other words, suppressing inflammation appeared to greatly reduce the anti-senescent effects of high intensity exercise.

The study also found a similar reduction in an inflammatory marker called CD11b 3 hours post-exercise, and this reduction was also diminished in those who took ibuprofen. In other words, levels of this inflammatory marker were higher after 3 hours in those who took anti-inflammatory medication, which seems counterintuitive. However, exercise-induced muscle damage results in a temporary period of inflammation during which immune cells ‘eat’ damaged cells and debris, followed by a period of anti-inflammatory activity during which muscle tissue is repaired. These two processes working together help keep muscle tissue healthy and youthful. The authors propose that the initial inflammatory stage sets in motion the subsequent repair stage, and that by inhibiting the inflammatory stage, ibuprofen disrupts the entire ‘inflammatory program’. 

The implications:

This study suggests that a rather low volume of HIIE exercise can trigger a brief inflammatory response, followed by a long term anti-inflammatory response that together suppress senescence and maintain healthy muscle tissue. It also suggests that the initial inflammatory response is important and that suppressing it with anti-inflammatory drugs might dampen the anti-senescent benefits. The authors note that some studies have shown ibuprofen to reduce muscle strength gains from resistance training, but only at high doses (1200mg/day, the same dose used in this study). There’s also a lack of data about the link between exercise, senescence and anti-inflammatory drugs in older people.