p53 in Cellular Senescence
Cellular senescence is one of the contributing causes of aging, in the sense that senescent cells accumulate in old tissues. Even when only a tiny fraction of all cells are senescent, their signaling causes chronic inflammation and disruption of tissue function. Senescence is, however, a helpful program when these cells exist only temporarily and are promptly destroyed. The signaling that is so harmful when maintained over the long term aids in wound healing and suppression of cancer when present for a short time only. Since the comparatively recent acceptance of senescent cells as an important cause of aging, the research community has spent a great deal of effort in better understanding the biochemistry of cellular senescence. The open access paper here is a representative example of the output of these scientific initiatives.
The classical depiction of senescence as a static, uniform, and irreversible cellular state has been progressively reconsidered, and senescence is now envisioned as a dynamic and multistep process. During the initiation of the senescence, which is also called as "primary senescence", the stressed cells may be still able to repair and/or eliminate the cause of the damage and then can escape from cell cycle arrest. For example, it was demonstrated that a small proportion of senescent embryonic fibroblasts were capable of reentering the cell cycle when p53 expression was suppressed through RNA interference.
However, these rare cases are considered to take place only in the early stage of senescence establishment. Moreover, persistent exposure to a damaging environment leads the cells to the next stage of senescence, known as "developing senescence", where cells are poised to demonstrate full-featured senescence. Nevertheless, if senescent conditions continue for extended periods of time, as it happens, for instance, in the aging process, the cells enter a third phase of senescence, known as "late senescence", in which they may be characterized by heterogeneous phenotypes such as flattened and enlarged cell shape, expanded lysosomal compartment and vacuoles, increased metabolic rate and reactive oxygen species (ROS) production, senescence-associated secretory phenotype (SASP) secretion.
In most of the models studying senescent cells, p53 (as well as the DNA damage response proteins) seems to be involved in the earlier stages, and the time factor plays an important role in the entire process. p53 activity decreases with time, and this is consistent with the idea of p53 (and p21cip1) being a crucial factor for the induction of the senescence and a gate to an early phase and still reversible senescence. On the other hand, the subsequent increase of p16 activity would be responsible for a late senescent state characterized by a distinct and permanent senescence phenotype, which is no longer reversible through p53 inhibition.
We need to spend more energy on trying to figure t how to suppress P53.
p53 has been identified has an inducer of ageing, with its chronic activation associated with a loss of subcutaneous fat and xerosis.
From my notes here are quotes from various studies: ( more suggestions appreciated!)
Piog had obviously increased the mRNA levels of anti-aging genes Sirtuin1 and Klotho, decreased the p53 protein level, and altered the expression of several genes involving cholesterol excretion, TG biosynthesis and inflammation in the liver.
A randomised controlled trial of 32 menopausal or sterilised women achieved mild improvement in fine wrinkling morphologically and amelioration in skin elasticity after receiving isotretinoin 20 mg three times weekly over a three month period. Histological results were largely comparable between both intervention arm and control arm of sunscreen and moisturiser. A significant reduction of epidermal p53 expression was observed in the isotretinoin arm.
FOXO4-DRI is the third therapeutic version in an evolutionary process of about a decade in research on FOXO4-p53. Right now, the selectivity of FOXO4-DRI for senescent cells is good enough for proof-of-concept experiments in experimental laboratory settings, but to truly allow for usage in humans, the safety profile needs to be even higher.
https://stardust.bio/article/73/foxo4-dri-therapy-explained-all-research-and-overview
from fightaging
where to get how to use
https://www.fightaging.org/archives/2018/03/how-to-plan-and-carry-out-a-simple-self-experiment-a-single-person-trial-of-senolytic-peptide-foxo4-dri/https://www.fightaging.org/archives/2018/03/how-to-plan-and-carry-out-a-simple-self-experiment-a-single-person-trial-of-senolytic-peptide-foxo4-dri
Finally, why does this article say ACTIVATING P53 is good when other articles say to suppress it ??????
Chinese skullcap
https://mypureradiance.com/hormonal-counterattack-2/
you can also find Chinese skullcap as a supplement. I recommend taking 400 to 600 mg per day with meals. Make sure you are buying a supplement, or the leaves, or an extract of scutellaria baicalensis. American skullcap (scutellaria lateriflora) is not the same and does not have the same biological effect.
* helps activate anti-aging genes in skin cells called P53 genes to prevent cell aging;