It is Plausible that Continual Removal of Senescence Cells Would Impair Regeneration and Limit Benefits to Life Span
The accumulation of senescent cells with advancing age is harmful. Selectively destroying those cells, even as few as a third of them, and even just once in later life, produces significant benefits to health and life span in mice. Cells become senescent in response to molecular damage, or to the signaling of nearby senescent cells, or on reaching the Hayflick limit on cell replication, or in response to tissue injury. In youth, senescent cells are rapidly clearly by the immune system and programmed cell death, but in later life the balance of creation and destruction is tipped towards an ever-increasing number of such cells.
Senescent cells serve useful functions prior to running awry in old age. They help to coordinate regeneration and suppress the incidence cancer. They secrete signals that attract the attention of the immune system, spur growth, and provoke the short-term inflammation needed to resolve issues of damage in the body. Thus we might suspect that a blanket and continual removal of senescent cells could be harmful in some ways. In fact, mice do live longer when all senescent cells are continually removed, but that may only mean that the beneficial outcomes outweigh the negative outcomes, rather than there being no meaningful negative outcomes.
The present consensus is that periodic removal of senescent cells, which does produce rejuvenation and extend life span in mice, likely has no meaningful downside. It would clear out the problem lingering cells during short treatments, while at all other times allowing for the temporary formation of new senescent cells as needed, such as in response to injury. This consensus may or may not reflect reality, we shall see as ever more data accumulates. In today's open access paper, researchers hypothesize on the question of why senolytic treatments to clear senescent cells extend median life span to a greater degree than they extend maximum life span in mice. Does that outcome result due to harmful effects that arise in later life to counterbalance the benefits?
This seems a question that is hard to answer, involving the need for a much greater understanding of the relative contributions of different mechanisms of aging at different ages. It is quite possible that any one given mechanism of aging, such as cellular senescence, is more or less influential on mortality in middle age versus extreme old age. That may not require any great difference in the details of cellular senescence in an aging body, but rather arise because another mechanism becomes more important in late life, for reasons that have little to do with cellular senescence, outweighing gains due to a reduced burden of senescent cells. Without intervening in these other mechanisms, it is challenging to say anything about their importance. We only know that senescent cell clearance is exciting as a basis for rejuvenation because it was successfully attempted. Prior to that point, there was no good way to assign a relative importance to the role of cellular senescence in degenerative aging.
Senolytics and the compression of late-life mortality
Whilst work continues to explore the possible therapeutic benefits of senolysis, we recently suggested that it is important to ask what evolutionary forces might have been behind the emergence of cellular senescence. Entry into the senescent state appears to be regulated, presenting questions about why such a response should have evolved. It seems a priori unlikely that a purely negative action would be favoured by natural selection. In terms of potential benefits, cellular senescence is often regarded as an anti-cancer mechanism, since it limits the division potential of cells. However, many studies have shown that senescent cells often also have carcinogenic properties. Furthermore, other studies have shown that cellular senescence is beneficially involved in wound healing, development, and tissue repair.
We recently brought these findings and ideas together and concluded that evolutionary logic strongly supports the idea that the latter positive contributions are the main reason for the evolution of cellular senescence. We further suggested that, since the immune system appears to play a role in clearing senescent cells once they have performed their temporary functions, the observed age-related accumulations of senescent cells might arise simply because the immune system had to strike a balance between false negatives (overlooking some senescent cells) and false positives (destroying healthy body cells).
The importance of understanding the role of senescent cells is further indicated by recent senolysis studies in mice, where it was found that treatment with senolytics resulted in a substantial increase in mean and median survival times. However, in each of the studies there was much less increase in the maximum survival time. Such an outcome is only possible if, following senolytic treatments, the deaths that are postponed to produce the increased mean / median lifespans become concentrated in the interval prior to the relatively unaltered maximum lifespan. Such a phenomenon constitutes a 'compression of mortality', which needs to be explained
We developed computer simulations of three possible mechanistic scenarios in order to gain a better understanding of possible modes of action of senolytic treatments. Scenario A, which supposes simply that senescent cells are all-important in ageing, was shown to be incompatible with experimental findings. Scenario B, which allows for other forms of damage to be involved and which also allows for senescent cells to drive these other forms of damage to some degree, was also found not to explain the data, although it does generate some interesting behaviours. In contrast, Scenario C proved to have the potential to explain the experimental findings. Scenario C includes the idea that the immune system plays an important role in removing senescent cells and related damage, but that this 'repair capacity' of the immune system is also negatively affected by senolytic drugs. In the case of a single senolytic treatment the repair capacity can recover, but if the treatment is given continuously (as in all the experimental studies), the repair capacity is chronically reduced. This leads to an accelerated accumulation of damage, causing a faster increase of mortality.
Hi there ! Just a 2 cents.
''...why senolytic treatments to clear senescent cells extend median life span to a greater degree than they extend maximum life span in mice. Does that outcome result due to harmful effects that arise in later life to counterbalance the benefits?''
Yes. It is (very) plausible that continuous removal of senescence cells would impair regeneration and limit benefits to lifespan. And as said, it could be an antagonistic pleiotropy explanation (of useful early in life/bad later then; or vice versa; as genes are turned on/off depending on the phase of life and can be benefitial or detrimental depending of the phase - because of 'later they will be bad/good, by then' (evolutive compensation/response)). It seems that senescence is not Entirely bad, that is some role in inducing skin wound/regeneration or helping it somehow (maybe it plugs it, helps for fibrosis/scarrification), that you need some 'minimum' level of senescent cells to maintain function; the body/cell biology adapted to this reality of senescent cells - so it is adapted to it; what if we remove senscence; this can hamper 'the previous adaptation' (to senescent cells)...
i.e. the body/cell/evolution found a way to have 'some use' for them- rather than just discarding them. That said, I think we can go quite low, but we have to be careful, because our skin capability for healing/wound repair needs to be preserved (this also is a bit at the crossroad with platelets needed for wound/closure; ''fight fire with fire''; the immune system could 'use' senescent cells; than just eliminate them - phage them (macrophage/NK cell).Too much immunity (autoimmune diseases), immune system attacks host/own body 'by error'; it could trigger inflammation (ROS) and senescent cell production - as a mechanism/an evolution compensatory answer; and we know senescent cells are ROS rich...ROS is not All Bad...ROS are used by the body/cells/mitochondrias because it/they have adapted to them - ROS are Ever Present (due to Oxygen Ever Present (on Earth on surface...for now and probablly the next million or billion years until we leave Earth or 'empty O2' on earth from too much CO2);
ROS can signal or rather 'trigger a signal' (that the body adapted mechanism - to the signal, by the ROS 'triggering it' (the signal)); this is same thing with CR (Calorie Restriction)...causing an Increase in ROS (temporarily), then activating the whole AMP pathway (Adenosine MonoPhosphate), instead of the ATP pathway (Adenosine Tri-Phosphate), this pathway is a 'energy sensing' pathway - when famine/drought, AMP rises...ATP lowers, the signal - > reduce mTOR, activate SIR, send SIRT into the nucleus (DAF-1/SIR/FOXO3). so, that you can 'resist' the famine/fasting/CR, because energy will lower by no more calories coming in. That is a 'mild stress' -> Hormesis - > mild ROS emission elevation - > Trigger Signal (ROS/mTOR/IGF/SIR) -> Benefit (by Evolution/hormesis).
Too Much ROS -> Senescence.
Too Little ROS -> Senescence (Also)
Just Enough/Less ROS -> No Senescence.
There a Tipping Balance aclled the Re'dox/Redox : ReDuced - OxIdized milieu. A reduced milieu is lower ROS/more quenching - up to a point; ROS can also elevate in a reduced milieu, not just an oxidized one; while Oxidized Millieu says it; it is more OX-idized -> Reactive Oxygen Species (ROS) oxidize the milieu by exposure of O2 to macromolecules/DNA/mito ETC (electron transport chain) for OXPHOS (oxidative phosphorylation/energy in mitos by using energy 'substrates' (pyruvate, succinate, malate; the main 3 that allow 'mito respiration').Which then form ATP (cell energy) from mitos. AMP is like a fail-safe mechanism or a 'poor man's version of ATP' (since it is mono phosphate; while ATP, is three/tri-phosphate). AMP is like a 'trickle charge' when sh*t gets rough...like you know, starving (self).....stressful, if it lasts very long (famine/drought/self-imposed fasting for days (uncontrolled/unmanaged)). No eating/no calories -> problem. Energy problem. Cell ATP levels will change/drop.
Thus, all this to say, there could a crossroad/crosslink/redundancy pathway that explains why senescent cells are not entirely useless/bad...and have some (positive) use also; So Long..as they do not tip the balance to 'oversenescence/mass senescence' because that is too much and leads the overt-senescence/cell causing excess ROS - which destroys surrounding cells in a vicious futile circle (more ROS -> more damage -> more senescent cells -> more ROS -> more damage -> m...etc).
Just like in the Redox; it'S a balance Between ''ROS emission VS ROS quenching'' capability; is ROS exceeds the quenching capability (such as being more than the Total blood ORAC (Oxygen Radical Absorbance Capacity (i.e.ROS Quenching Capacity), SOD/CAT/GSH/Tocoph/ Thiols/Albumin/bilirubin/HSPs/HEME-1 (Heme-Oxygenase-1/Chirotoptic (iron Fe+ chelating) enzyme (because iron mineral is needed for health/muscle -> massive ROS producer by Fenton Reactio with Iron; Fe + ROS = Fe Radicals -> H2O2 (hydrogen peroxide) -> MDA/TBARS (malondialdehyde/LipoPeroxidation/Thiobarbiturates))/HIF (Hypoxia Inducible Factor)/ etc..., all the first defenses against excess (these) ROS oxidation phenomenon - from Breathing O2)). O2 is not only contributor but itself is a substance that 'ages' the clock - it signals the epilock to move forward - not just produce ROS/oxidation/peroxidation; thus, it has a 'aging clock' (signaling) role (separate from its ROS contribution). Or, inversely, let's say, is that the clock 'recognizes' the substance as an 'aging' substance; it Does That to it. The O2 could be Absolutely Inert..and do nothing to the clock; but the Clock Itself - Decides/is Triggered - into Continuing upon cell exposure; therefore; O2 would be a 'trigger' (or signal) to it; it's not so much the damage (causing epiclock advancing; although it does..); it is the 'nature' of the element - itself. Oxygen and Peroxidation/Oxidization phenomenons just 'rust' the clock. Not just your body/cells; your clock is a part of your cells..so obviously if the cells were damaged - so woud the Clock Be...but it'S more nuanced than that. The CLock could Be Inert Even So. Even if I give myself 100% HyperBaric oxygen/Hyperoxygenated/HyperOxidation....
But, we See Rather, that Indeed..the exposure to whatever leve..Will Change the Clock/make it run its course. I think that Oxygen gives life and we know it came to be on Earth..because of ancient unicellular bacterias 'starting life' 3 billion some years ago whence it was Gray and Dull...and raining...all the time and Volcanoes/PLumes eruption everywhere...and just a landmass of nothing but cinder/ashes....and micro bacterias..just like on Mars same thing or Moon. It was the Debut of the Debut..Oxygen allowed Symbiosis and Osmosis; it allowed cells to become more than unicellular..multi-cellular; and especially, to nuance, to have Bacterias - be Hosted - by Unicell. Like our Own very cells which are Bacterias..techniaclly speaking. Like our Mitochondria - is a Bacteria (from 3 billion years ago whence it 'joined' a unicell...with time there was a symbisos that happened; mitochondrais 'made energy' for the cell 'as return gift' for 'being housed' inside the cell 'The Host'...just like a baby in a mother'S womb same thing.
Baby (Hosted), Mother (Host). Now, this an evolutive adaptation; to allow 'complex animals' to become (multicellular animals) - oxygen was produced By Bacterias (like mitos in our cells); they fed on Sulphur/methane gaz (it smelled like rotten eggs (methane gaz/farts are methane gaz) billions year ago) back then and decides to start making this 'Oxygen' and then its was 'Ozone' (our Ozone layer (O3 (Ozone), O2 (Oxygen); then the oxygen was a 'fuel' that energized the cell (O2 -> cell -> mito -> ATP -> cell 'Alive' -> Organ -> Tree/Animal (animals on ground -> water/aquatic animals using less O2 (less O2 in water))) -> Faune/Animal Kindgom (3 billion years later). Oxygen is truly our fuel/energy of life.
I'm strayinh a bit here (sorry, it's friday night TGIF (a long friday by this long message (sorry))).
But to finish, I think senescent cells have not said their last word..they ain't going nowhere, they be stayin' - in us. We can extract them all we want...but they haev some minor benefits..but obviouslt far more negatives; thus senolytics are the way...we just have to dose them...senescent cell removal (p16 cells) gave 20% medium lifespan extension..so we must not think so much more of that (we have been eating senolytics in Food since godknowswhen; (-god knows (if you even believe or think is baloney (like rejuvenation - all baloney scifi) -..since birth).
I think they could give us the chance to live healthy to 90-110; might make us live 120; but that is Genetics(Epi-Genetics); the genetics have the final say...not (just) the environment...of course environment/Food/stress/exercice...all that major impact on Health-..but not all entirely on the Longevity/Maximum Longevity; that is epidomain/DNAdomain/Chromosomes 101. And yes damage to it (to DNA/macromolecular damage/especially nuclear/chromosomal damage causing Havoc and epigenetic Drifting 'aging' -> Shorter Longevity). We have come to the capacity and capability of comparing a micro ant vs giga whale...and we can tell. Thus, we can solve the senescent cells no problem. They are not the entire explanation of longevity; just one of them; not the Main one. Senescent Cells Happen...they get removed and can contribute to health degradation by loss of stem cells (will deplete as they try to 'repair on and on'...niche depletion);
tissue destruction - that is what is called - accelerated loss of 'health (threshold)' maintenance; it is why you Can Die Young Too; meaning you are Younger - Per the Clock - but you did Not Maintain the health - thus, Premature Senescence -> p53 -> p16. (While replicative senescence is p53 -> p21; this oncogene Does Not show during 'spontaneous senescence' from excess ROS/damage Rapidly); while Replcative Senescence Over a Long TIme (like...a lifespan..multiple cell cycles happened); this will Activate the p21 oncogene/tumor suppressor gene; this one Causes Replicative Senescence. Thus, we can differentiate what happens with maintaining health..in young people vs old people;;and why...a a centenarian is Healthy (enough) and there is Morbidiy Compression in old age - keep healthy Longer...those people dying Younger...can be 2 things...either there 100% Older per the clock or they are 100% Younger...but did not maintain their health - Premature Senescence (this was demonstrated in people with fast progeria (HGPS) vs Werner syndrome (mild progeria) vs Normal people (dying 60-90 years old) vs slow agers/genetic-luck people who reach 100-115.
Some of these Normal people are actually Older biologically than their chrono age; or Younger...the younger they are the more they post-pone death; but do Not Stop Death..they may still die Much Earlier in their Young(er) Age..of whateever disease (that is wht you see children die of diseases..they Are Younger...per the epiclockl...yet died...of a disease. in such young age). It means that there is a fitness/health/frailty 'threshold' that must be maintained at all times (for organ function) - in all a human's life - to Continue a Life - to Its Maximum/Longevity Possible (for human individual/specie).
Just a 2 cents.
Yes, it is very plausible
and people like Dr. Campisi and others have been flashing a red flag about this for years
Simple, use thymalin and vitamins that create new t cells after your done with the senessent killing. dosent need to be harder then that.
If there was any truth to Scenario C, we (Oisin Bio) and others (for example, Mayo) would have reported reductions in median survival. We did not do so because we did not see a problem with repeated, transient administration of therapy on one month centers in our case, or even one week centers in Mayo's transgenic mouse experiments. Thus a precise definition of "continuous" is needed; no one in the senolytic community is arguing for daily dosing.
And, in addition, in much larger internal studies we have seen that if one doesn't persistently remove SnCs on a regular basis from aged individuals, the benefits fade with time as SnCs repopulate. This is to be expected; there is a "sweet spot" that needs elucidation, no question about that. For mice, that repetition rate is perhaps one month or more between treatments, for humans it remains to be determined but is likely to be significantly longer in our opinion.
senolytics do not address the core primal reasons why we age - epigenetic and telomeric clocks and whatever other 'clocks' are in work. All of these are unrepaired damage, just some are selected by evolution and encoded in genome like epigenetics and telomere maintenance (which is also epigenetically controlled), and others are not encoded in DNA. Hence limited individual senolytics life span extension - little enough so it do not exceed the longest possible lifespan for a given specie. The real utility of senolytics is that SASP blocks epigenetic and telomerase repairs thus for us old folks normal ways of restoring telomere length and epigenetic age do not work, unless increased to cancer level (ie. at least magnitude greater than otherwise required for infinite self repair). Cheaper, safer (already known methods) that weren't working, will be working combined with senolytics.
@CANanonymity:
What do you think about the daily use of antioxidants like astaxanthin?
Removing all or almost all of the senescent cells in an older human would almost certainly be adverse. But I don't believe we are close to achieving that end point. As I see it SCs accumulate in old people because the systems that regulate them have fallen into disrepair and need a helping hand similar to how we now take medications/supplements to regulate insulin or hormones.
Hi Alex! Thank you for that. Just a 2 cents.
I have pondered a Lot about this antioxidant (especially when I was at my worse/in atherosclerosis purely);
The first thing, it is not Bad per say, to do so; albeit it has limited 'reach'/effect...it reaches pretty deep; Astaxanthin (found in several fruits mostly; like gojis/berries) was detected in mitochondria or truly in cell, and was able to do powerful quenching. It is why they said it was such a powerful antioxidant (a bit like Zeaxanthin (yellow pigment, in corn), another like of the xantophils; xantophenols); therefore it acts where it matters (ROS production in mitos, is reduced by it) a great thing.
But, it was found that antioxidants are a double-edged sword; you need some of them (basic protection) but you also need Less of them (also - you should be able to Do Without Them); I mean we need to quench oxidation, thus in that sense Astaxanthin really helps; it is why it improves health; but antioxidant often are 2-faced/double-edged; they can turn Pro-Oxidant; many do (once in body); Astaxanthin (if I remembeR) is one that does not (as is natural - but only if Itself is not Oxidized when consumed (Oxidized Astaxanthin is mostly poison if it just contributes to oxidizes the thiol pool in your blood (Thiols are your Largest Protection in your blood/anitoxidative capacity), if it somehow 'activated the Main Thiols/Phase II Detox Enzymes/NRF2/ARE/eRE (Nuclear Response Factor-/AntiOxidant Response Element/electrophile Response Element (GST Transferase/GSPx/GSH/SOD/CATALASE...etc) these are your enzymatic/non-enzymatic ROSDetox Protection and Astaxanthin can help or hinder them - be 'competing' or 'in their way'...thus, you have to find the dosage and timing with consuming certain antioxidants (be it fruits or synthetics..);
Mnay studies have been done and refute the 'Antioxidants Make Longevity'. Thus, Antioxidants are now just a 'thing' you can do to keep health; but it has been shown that antioxidants can be Detrimental (especially, if they turn prooxidative); and studies said: ''we did not see Any changes to lifespan from antioxidant consumption - in fact we saw Reduction of lifespan from antioxidant consumption)..that means 'double-edged'/'competition'/when antioxidant turn bad/''when less is more''. It's incredible because in longe-lived animals like parrots or pigeons they saw 'potent' antioxidation - but only If Needed...it was needed..when it was called it was potentially damaging (a bit like 'bilirubin/biliverdin/biles...'..this is Very powerful antioxidant in your body (people with GERT disease or birds (like parrots) have much higher producion of liver biles components; it quenches ROS on much higher magnitude and much Larger/Wider/ Spread...
But. It causes severe damage too bt formation of 'Rocks - Crystalized like stones,... called 'Kidney Stones'..that ruptured the kidney tissue/renal failure (if these biles stay too long). HEME-1 Oxygenase can call/use these biles to quench iron/heme Radicals..it's what happens when your body is Extremely stress (HEME-1 Oxyg. is called and then the body slows down/metab and tries to mitigate the damage from Overtstress; it does granulation (formation of granules to slow down protein/DNA synthesis (via eIF1 (eukaryotic Initiation Factor-1), to not 'choke' on the stress; well it sorts of 'chokes itself' - to no choke (of stress); but it's like a 'damage-control/fail-safe alternate 'slow' 'Hard' mode'.
To end, I decided to forgo consumption and try to work on minerals/vitamins (which I know are not 'saviours' but they have Far Reaching effect because our body produces/needs them Naturally); I consumed goji baies/juice and it is powerful, for me, at that time, it was too much - it made me sick (it is why, is it important to Gauge your Current Health..if you wish to consume it, it may Improve your Health (or depending if unhealthy) it may Worsen your situation; because, things are dual-nature/2-faced Very oftenly; even more so during a bad health i.e. what was good (thence)..is bad (now); it resembles a lot the whole 'Antagonisitc Pleiotropy - 2face thing - a time (and a 'timing' (and dose)) for everthing').
Just a 2 cents.
There are studies epoch plausibly show that some senescent cells are needed for wound healing and if they are missing the healing is impaired . https://www.sciencedirect.com/science/article/pii/S1534580714007291 .
However, it would need a simple and short study to investigate a continuous administration of senolytics before, during, and after inflicting a wound. It might turn that different tissues show different affects.
Another possible (meta)study would be to compare wound healing of navitoclax and dasatinib users, who for example, have undergone a surgery
@CANanonymity
"One of the main relevant evolutionarily-conserved transcription factors modulated by astaxanthin is the forkhead box O3 gene (FOXO3), which has been recognized as a critical controller of cell fate and function. Moreover, FOXO3 is one of only two genes shown to robustly affect human longevity. Due to its tropism in the brain, ASX has recently been studied as a putative neuroprotective molecule capable of delaying or preventing brain aging in different experimental models of brain damage or neurodegenerative diseases. Astaxanthin has been observed to slow down brain aging by increasing brain-derived neurotrophic factor (BDNF) levels in the brain, attenuating oxidative damage to lipids, protein, and DNA and protecting mitochondrial functions. Emerging data now suggest that ASX can modulate Nrf2, FOXO3, Sirt1, and Klotho proteins that are linked to longevity. Together, these mechanisms provide support for a role of ASX as a potential geroneuroprotector."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401246/
"It is assumed that, ridding the body of aged cells, the senolytic should activate regeneration processes that will replace the "released space" occupied by old cells with new cells. However, in practice,especially in the case of certain tissues of the old body, such replenishment does not always occur. For example, Pax7-expressing satellite cells, which are formed at the embryo stage, are indispensable for the regeneration of skeletal muscle in adults, and the depletion of their pool leads to myopathy [12, 13]. Similarly, the loss of skin fibroblasts is usually not accompanied by replenishment with new cells - fibroblast membranes extend to fill the emptyspace of lost neighboring fibroblasts instead of proliferation [14].Moreover, in some cases, senolytics can even reduce the functionality of tissues. In particular, the use of one of the senolytics, dasatinib, caused endothelial dysfunction and pulmonaryhypertension [15], which could be corrected using ROCK inhibitors. " From: "Can a combination of senolytics with ROCK inhibitors and 5-LOX inhibitors contribute to tissue rejuvenation?"
https://www.academia.edu/43246320/Can_a_combination_of_senolytics_with_ROCK_inhibitors_and_5_LOX_inhibitors_contribute_to_tissue_rejuvenation
https://docs.google.com/document/d/10onyRyohpZPwRnPUyMpBSfuGWOlqS489Xe5WEZNrVDQ Also: "Muscles retain positional memory from fetal life" see https://ewww.kumamoto-u.ac.jp/en/news/468/?fbclid=IwAR1YXeKZPg_3ZxnE551G2NMXBpOkaIPUOzcYWjveCNqgS6ELv18hMXKbq60
Continual Removal of Senescence Cells... Isn't that exactly what a properly functioning immune system does and only stops doing if compromised?
I think a combination of senolytic therapy and regular infusions of biologically young stem cells could be what is needed to move the needle on maximum life span. You need to replace what is lost, not just remove the bad.
Hi @Alex Do you have any idea what a reasonable dose of astanxanthin might be?
It's been a while since this forum has discussed oneskin topical supplement for skin aging. We are halfway through 2021 and I can find only one review. There has been enough time to see if users have actually reversed skin aging. Is this a holy grail or not. I would appreciate any comments about your results to date.
Re Alex, Thank you for that! Just a 2 cents. Astaxanthin is not bad, as I said, the study you linked does show lots of potential (activating important detox ros quench pathways FOXO/SIRT/ROS scavenging and even increase BDNF levels (what's not to like, which increase when you reverse aging or let's say improve health, brain health, neutrophic factors rise - neuron health/geneartion, stop brain pruning (gray white matter) that do slow down aging or improve health, obviously, then it would make sense to consume it), but that can be said of other antioxidants 2-faced that can do this (too)...IAll I'm saying, is if it works for you, it works. If not, it does not. There are many shades of gray in aging. Overall, there is more Good to consume than bad. I know you may think ''What does it take to convince you then, this study says so - in writing by biologists, are you tonedeagf?''. IT's because there are Other studies that studied these antioxidants and did not always come up with the same positive response (now I know we are talking about Astaxanthin - this one is Very Good/highly protective and as per the study activates a plethora of protecive pathways); if many studies say so it makes sense, but we should not discount/just dismiss any contradictory study or a study that says : ''mice saw no max lifespan extension from astaxantin...but imrpoved their health and median and avg lifespan''
This happened to me very oftenly, I thought that 10 studies said the same thing therefore that was the truth/but then, som Other study came along, and refute that. I felt almost duped/oops. It's the old : ''smoking is good for yuo.....smoking is bad for you....smoking is good for you...smoking is bad....covid vaccine is good for you....covid vac is bad for you ... covid is good for you........''; who do you believe anymore? Thus, in biologi and biogerontolgoy specifically you ahve to Take Some and Leave Some (moderation is the key or has the famouse doctor newton or socrate/platon: ''(in medicine) the dose makes the poison (or the cure)''). That applys ot almost anything, even supplements (like antiox). Just a 2 cents. (I will re-add astaxanthin at some point, it is a powerful antioxidant like MitoQ, Ubiquinol, alpha-tocoph (VitE) or melatonin hormone, or other phenols (zeaxanthin/lycopene/beta-carotenoids - it was demonstrated that centenarians have Higher Levels of carotenoids in their brain; this demonstrates potent quenching capability of xanthins, carotenoids, cyanin, flavone and other phenols; to make a long lifespan (like them)). This falls in the ORAC, consuming antioxidants from fruits (that contain astaxanthin) improves health by having more blood ORAC ROS lag, thus just a blood that is 'antioxidative rich'; which means more ROS lag (like in atherosclerosis - LDL Ox Lag - ORAC - astaxanthin will lengthen LDL ox Lag (the moment is becomes oxidized and contributes to formation of atherolesions/plaques). What I had learned is that there is toxicity (threshold) to a Lot of stuff consumed; (dose makes poison or cure). As my father said : ''My mother use to say : ''If you eat a 18Wheeller vanderbilt truck size load of oranges...............you will die''.
(And we know oranges are healthy, full of citrus phenols, but eat a truck of 'em and you/it will be (the) last orange; you can even die of 'water poisoning/water toxicity by excess drink if you drink like 10 liters of water; it will mess your salinity/osmos/pressure in blood/water fluid/mess electrolytes/minerals - death; anything (good) can be (bad, too)). Thank you again for the study. PS: Sorry for my pessissim (I just worry sometimes (often/anxiety; atherosclerosis = anxiety massive, anxiety = keep alive; we need reality checks - to feel alive)).
I'm with Jones' thinking here...
Is aging primarily immune systems aging.
It seems that's the most upstream target.
@Chuck Frasher:
Hi Chuck, I personally take 12mg a day of Astaxanthin sourced from Microalgae Haematococcus pluvialis (it's recommended in the dosage range of 4 to 12 mg daily).
@CANanonymity:
I understand the meaning of your words. In fact astaxanthin does not appear in many studies on anti-aging molecules. In my humble opinion, asx is like a "special nourishment" for the health of the mitochondria and affects aging.
There seems to be a missing element in this approach to senolytics: Does the senolytic agent clear ALL senescent cells, or only those with certain characteristics? In a recent interview posted by the Foresight Foundation, James Kirkland said that the mechanism by which D+Q senolytics works is that it removes the immunity of a senescent cell to it's own toxic SASP production, and that senescent cells not producing SASP are not cleared. If that is correct, it would appear that the worries about clearing "good" senescent cells goes away.
It's also true that some senolytics can cross the blood-brain barrier while others cannot. This means that effects on senescent cells of the nervous system may vary with the senolytic technique used.
@John G. Cramer
very good points. On an intuitive level it wold seem that senescent cells which don't secrete SASP are much less harmful , except for the fact that they might not function as well as "normal" tissue cells. I think that there's are many spectra from of senescent and near senescent cells with quite different characteristics and vulnerability profiles. Also, i think that the senescent cells which are good for growth and wound repairs are of a different type from the ones that linger. With precise enough treatment we still could keep those while eliminating all of the inflammation. This , however, would come at generation 3 or 4 of senolytic treatments.