Delaying Age-Related Pathologies via Senescent Cell Clearance: Applications and Future Consideration

Updated: Aug 22, 2018

By Julia Sjoquist


As your body ages, so do your cells. Some cells malfunction and proliferate out of control resulting in tumor formation. Some are unable to regenerate, decreasing the body’s ability to discern between incoming stimuli whether that be smell or vision. And some remain as they are, unable to die and unable to form new cells. An aged cell trapped in time. Stagnant.


It is these types of cells that build up naturally in the body’s tissue as we age. Most senescent cells express p16Ink4a, a cyclin-dependent kinase inhibitor and tumor suppressor which sounds like a good thing. And in most cases it is, but recent theories suggest buildup of senescent cells and the chemicals they secrete actually interfere with muscle function and structure, resulting in age-related pathologies including cataracts, infertility, cardiac arrhythmias, arterial wall stiffening, or fat loss. Recent research indicates p16Ink4a-expressing cells can be moderated with certain treatments, introducing larger ethical questions regarding therapies for enhancing health.

What Baker et al. addressed in their 2011 (and subsequent studies) was if and how senescent cells factor into age related pathologies, and was it possible to prolong healthy life with cell clearance.

Art by Macy Chutoransky

The answer was yes to both posed questions.


Using an extensive transgenic targeting strategy, Baker et al. managed to destroy p16Ink4a expressing cells in a specific mouse model, BubR1H/H, that mimics ageing in humans (aging was defined by the expression of age-related phenotypes like infertility, lordokyphosis, cataracts, dermal thinning) and location of senescent p16Ink4a cell accumulation, notably in the eye, adipose tissue and skeletal muscle.


Baker et al. found that life-long clearance of p16Ink4a cells delayed the onset of age-related pathologies, when compared to untreated mice. But only in certain tissues such as the eye, skeletal muscles and adipose tissue. Aorta tissue was not affected, presumably because there was no localized expression of p16Ink4a to use for targeting and destroying senescent cells. Thus the mean life-span of the treated mice was not significantly longer than the untreated mice, since most of the deaths were attributed to cardiac failure from arterial wall stiffening and cardiac arrhythmias.


That being said, p16Ink4a cell clearance did prevent or delay the onset of age-related disorders (like lordokyphosis and cataracts). In addition to skeletal muscle retention, the duration, distance and overall amount of work performed on the treadmill exercise tests were all significantly increased when compared to untreated mice. Improvements were also seen with late-life clearance, increased muscle diameter, and increased muscle endurance. And fat deposits and adipocyte size were both larger in treated mice, as was subdermal adipose layer thickness.


Thus, in these three major tissue types: skeletal muscle, adipose tissue and eye tissue, age-related pathologies could be combatted simply by clearing out senescent cells both in late-life and life-long treatment. This theoretically opens the possibility for future clinical treatment of ageing.


But this research leads down a controversial path.


The use of “slippery slope” is an overused cliche when referencing new scientific findings, but it is important to think forward and think critically about shiny health-boosting therapies pioneered by researchers like Baker et al.


Will clearing senescent cells enhance the quality of life, or just the quantity?


Will the clinical treatment of ageing be seen as a luxury? Used then only for the upper class?


Will prolonging life affect how resources are allocated in society?


Baker’s experiment suggests that delaying or perhaps reversing age related pathologies is possible. Although research into prolonging life is just starting, and it will take time before we see any human testing or clinical treatments, know this: the race for immortality has begun.


References:

Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., Van De Sluis, B., ... & Van Deursen, J. M. (2011). Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature, 479(7372), 232-236.

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