Today I thought I'd share a recent commentary on cellular senescence research to treat aging. A growing amount of work is taking place on the fundamentals of clearing senescent cells as a method of partial rejuvenation. The presence of newly founded companies pushing forward towards clinical translation, and results showing life extension and improved tissue function in normal mice are drawing more funding into the field. Folk in our grassroots community are also helping where they can, such as by crowdfunding the first studies to be carried out by the Major Mouse Testing Program earlier this year, or providing seed funding for promising companies. All of this effort is not before time: it is nearing fifteen years since SENS rejuvenation biotechnology advocates first gathered the evidence supporting senescent cell accumulation as a fundamental cause of aging, and began calling for more research on this topic. Various research groups are now focusing on different methods of clearance and their effects on specific tissues and organs, seeking to prove or disprove effects on degenerative aging. We should expect to see a mix of benefits and absence of benefits once the dust settles: senescent cells are only one of the seven broad classes of age-related damage enumerated in the SENS research proposals. Their presence may contribute to many or even all of the common age-related conditions, but they are not significant causes of all of the specific forms of secondary and later cell and tissue dysfunction in the aging body.

To pick one example, earlier this year researchers published a study of the effects of reduced senescent cell counts on aspects of vascular aging. It was indeed a mix of benefits and absence of effects: fewer senescent cells led to reduced calcification of blood vessel walls, associated with blood vessel stiffening with age, but it didn't have much of an impact on the development of atherosclerotic plaques. Both of these items are about as serious in their consequences over the long run. Stiffening of blood vessels drives hypertension, which in turn produces damage to delicate tissues such as the brain and kidneys as tiny blood vessels suffer structural failure at a greater rate. It also provokes remodeling of heart tissue, leading to heart failure, and along the way helps to turn atherosclerosis into a fatal condition. The fatty, inflamed plaques that distort blood vessels eventually grow to the point of rupture, which either blocks or breaks important large vessels. That is a frequently fatal occurrence. This mixed outcome was an interesting result, as one of the characteristics of senescent cells is that they produce greater levels of chronic inflammation via the mix of signals they generate, the senescence-associated secretory phenotype. This signaling is how small numbers of senescent cells, perhaps 1% of the cells present in an organ, can distort the function of the other 99%. Inflammation is pretty important to the pace of progression of atherosclerosis, so one might expect a reduction in the number of senescent cells to slow the pace of that condition - but apparently not in this particular scenario.

The recently published commentary linked below is a celebration of the fact that the scientific community has finally achieved some traction in the matter of a treatment for the root causes of aging, one likely to produce reliable, if partial, degrees of rejuvenation. It is not unreasonable at this point to expect senescent cell clearance to achieve larger and more robust results on aging and age-related disease than much of the rest of present day medicine, and to do so in a way that is additive to other methodologies. That capability will emerge fairly soon in clinics, a few years to a decade from now, varying with the regulatory environment and where the products are offered. This is the true benefit of focusing on reverting the fundamental damage that is the cause of aging, rather than tinkering with later stages of disease and malfunction.

Senescent cell death brings hopes to life