Throughout the research community, scientists involved in the study of aging, inflammation, and various age-related diseases are retrofitting the present appreciation for senescent cells into their past work. Over the past few years, the scientific community has suddenly awoken to the fact that the accumulation of senescent cells is a significant cause of aging and age-related pathology. This sea change of opinions could, in principle, have happened at pretty much any time in the last 30 years, had resources been better directed within the aging research community. But prior to a decade ago next to nobody in the establishment hierarchy wanted to listen to or acknowledge the potential for treating aging as a medical condition, as a pathology with causes, despite the enormous amount of evidence for that position.
But now a different scientific culture has taken hold in the study of aging, bringing with it a newfound willingness to consider the treatment of aging. There is a new acceptance that aging has causes that can be addressed, and that the inflammatory signaling of senescent cells is one of those causes. Thus papers like the one noted here are starting to emerge, picking up on a prior finding and tying it to the biology of cellular senescence, now more widely appreciated. It may well turn out that a good fraction of approaches shown to modestly reduce chronic inflammation in aged animals will turn out to act by in some way dampening the signaling of senescent cells.
As a basis for therapy, suppressing that signaling while leaving the cells intact is far inferior to the senolytic therapies that selectively destroy those errant cells. Suppression is rarely complete, while destruction removes all issues. Examples such as the one below, compounds already widely used and extensively investigated, are very unlikely to be capable of producing large effect sizes in humans, but it is nonetheless interesting to watch this great rethinking of past data as it progresses.
Tocotrienols (T3) have been shown to represent a very important part of the vitamin E family. Experiments conducted in both mice and humans have shown potential health benefits from T3 supplementation, including a distinctive and effective anti-inflammatory activity. The anti-inflammatory activity of T3 has been also proposed as the main mechanism of action of T3 explaining the amelioration of conditions related to a diet-induced metabolic syndrome in rats. The anti-inflammatory activity of T3 has been also proposed to contribute to their protection against neurodegenerative diseases, including Alzheimer's disease (AD).
In this review, we summarize the broad range of anti-inflammatory effects of T3 on aging and the main age-related diseases with the aim to provide a common mechanistic rationale through which tocotrienols may exert their pro-longevity and pro-health action. In particular, we suggest that part of the anti-inflammatory effects of these natural compounds can be due to their modulation of the senescence-associated secretory phenotype (SASP) produced by senescent cells, where their accumulation in aging has been proposed as a key pathological mechanism in different age-related pathologies. T3 may act by a direct suppression of the SASP, mediated by inhibition of NF-kB and mTOR, or by removing the origin of the SASP through senolysis. As a consequence, many age-related pathologies connected with the SASP may be attenuated or prevented by T3 treatment.