Senolytics as a Treatment for Aging and Immunosenescence
Senolytic drugs capable of selectively destroying senescent cells in aged tissues are probably the most immediately promising of present efforts to treat aging as a medical condition. It is unfortunate that so little work presently takes place to rigorously evaluate the well established low-cost generic drug and supplement senolytics in human patients, as the animal studies suggest that they could be very beneficial. Unfortunately the high costs of running clinical trials ensure that low cost treatments receive little attention from the biotech and pharmaceutical industry. The dasatinib and quercetin combination is at least demonstrated to reduce the burden of senescent cells in humans, and is prescribed off-label by some anti-aging physicians, but large clinical trials are needed to be able to say in certainty that human use produces some degree of rejuvenation.
Aging is a multifactorial process driven by various intrinsic and extrinsic factors, including genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. These factors are closely related to organismal aging, and research has shown that inducing them can accelerate aging, while intervening in them can slow down, halt, or even reverse the aging process.
Among these factors, cellular senescence is a key contributor to organismal aging. Targeting senescent cells (SCs) holds promise for developing novel and practical anti-aging therapies. Cellular senescence is an irreversible state of cell cycle arrest caused by various factors, such as DNA damage and telomere shortening. Additionally, the process whereby immune system function gradually declines or becomes dysregulated with human aging is known as immunosenescence. Although considerable variability in aging exists among individuals, the aging process generally involves chronic inflammation, tissue homeostasis disorders, and dysfunction of the immune system and organ functions, readily causing cardiovascular, metabolic, autoimmune, and neurodegenerative diseases associated with aging.
Existing research indicates that transplanting SCs into young mice induces bodily dysfunction, while transplanting them into aged mice exacerbates aging and increases the risk of death. This suggests that SCs accelerate organismal aging. The specific reason is that SCs release the senescence-associated secretory phenotype (SASP) into the tissue, promoting chronic inflammation and inducing senescence in surrounding tissue cells and immune cells. SCs and chronic inflammation interact and crosstalk, forming a vicious cycle of inflammation and aging. Therefore, in-depth research into the key characteristics and underlying mechanisms of cellular senescence, immunosenescence, and inflammation, identifying drug intervention targets, and developing targeted interventions can help mitigate aging and aging-related diseases, thereby promoting healthy aging in the elderly.
We will all probably all be dead before those human randomized control trials are done. It does not concern me though because I am already intermittently mega dosing the best known senolytics individually at the maximum rate my 64 year old body can reasonably handle, that being 3 times a month since it takes me about 3 days to recover from any one mega dose. When I turn 68 I think I can provide credible testimony on whether they worked for me or not. Fisetin, D/Q, Apigenin, Piperlongumin, Grape seed extract, Kaempferia Parviflora
I've done D+Q or D+Q+F 3-day high dose senolytic sessions every 3-4 months for the past several years. I think they make me more fit, but for me they induce flu-like symptoms for a day or so, followed by several weeks of feeling better than average. The senolytics is suppose to induce apoptosis in some senescent cells. I have recently learned that on the cellular level apoptosis is quite energy-expensive, in that cleanly disassembling one average cell requires the energy from around 1 to 10 million ATP molecules. If one forces apoptosis when that required amount of ATP is not available, the cell will die in ugly and toxic necrosis. I'm old enough to have accumulated enough mtDNA damage to have a short supply of ATP, so I'm wondering if the flu-like symptoms are a consequence of inducing cell necrosis rather than apoptosis,
Which physicians do prescribe D+Q ?
@Josep: The Life Extension Foundation maintains a physician directory, and that's a place to start. Alternatively, try searching in the usual way for nearby anti-aging clinics and calling them up to ask. There is also this list as a starting point for that sort of activity: https://age-reversal.net/physician-directory/