Mice and rats used in research, have had their husbandry steadily improved, (and obviously live longer than in the wild), with long lived strains developed (which didn’t even happen with humans - we didn’t develop a strain of long lived humans). And it is in these well cared for animals living in protected environments (lab environments are even more protective than free living humans), that we tested rapamycin and achieved substantial max lifespan extension on top, thus validating the efficacy of this drug. In fact, we are so attuned to avoiding the effects of poor genetics or poor hubandry, nutrition and environment, that we exclude all those limitations by insisting that only long lived rodents are used as controls, thus assuring that we are not comparing to subpar cohorts. That’s what Matt Kaeberlein’s 900 day mouse rule is all about.
And the same is true for companion animals such as dogs and cats. Veterinary science and pet care have evolved to the point where the longevity of our pets have reached new records. It is in this context that studies of longevity interventions including with rapamycin have been and are being conducted by scientists like Matt Kaeberlein on pets that share our environment.
And in general our knowledge and care for lab animals and zoos has grown dramatically in the last century where the animals are of course living incomparably longer than in the wild or in captivity compared to a bygone era. I think it’s safe to say that lab animals are cared for with greater attention to their health than the average human out there.
One thing that’s omitted here is that we DO have human data. It’s complicated by being in transplant patients, but the transplant literature is the closest thing we have to long-term human outcome data on chronic mTOR inhibition, and it’s not cited enough in my opinion in these longevity discussions. It supports a real anticancer effect. It does not cleanly support “sirolimus extends transplant patient lifespan” as a settled fact, but these are complicated transplant patients on many many medications and they are also on continuous immunosuppressive dosing, not the pulsed dosing, and they STILL have lower cancer rates. So there’s definitely a signal there in humans.
@splarme That’s certainly been my experience. I’ve been on Rapa for 6+ years and I’ve had a few where I didn’t feel my best, but I have maybe been actually sick twice.
I would like to see some anecdotal reports from people using Sirolimus who have managed to live beyond the average.
Is it too early to see this? Has anyone tried to find out?
Does anyone know how long a significant number of older people have been taking Sirolimus off label for longevity puposes, just want to get a feel for when we may see these anecdotal reports
Well, we have one in these boards that is 86 or 85 and going very strong. He’s been taking it for over five years. There’s couple other’s in their 70’s that swear by it and say they feel much younger and better than ever (could it be placebo, I don’t know).
Anybody that has been using Rapa for that long at this time is not normal. Probably doing 20 other things too and eating healthy. A great many people don’t do the sleep, eat and exercise. It’s a really tough job to figure out whether to take a drug or not and we won’t get anything at all from what we have now.
This is true. Most of us are taking a bunch of different things to have an additive effect because whether we live longer with more healthspan matters more to us than knowing which specifically helped us the most. It’s just human nature.
Interestingly, general cat lifespan has dropped precipitously over last 35 years in my practice. In the 1990’s I would always have 5-10 cat patients at around 25-26 yrs of age, (in the last years of their lives.) And up to 50 cats patients, from 19-22 yrs. And an average life expectancy of 15yrs. Now I never see a cat live longer than 17-18yrs and an average lifespan that is closer to 12. The number one issue I feel, is that most cats in the 80’s and 90’s were outdoor cats and had significantly increased muscle mass from being active. Outdoor cats now live a much shorter life due to the influx of coyotes, feline aids virus, disc brakes!( because no one could drive fast around corners in the 80’s with drum brakes). Cars just generally being so much easier to drive faster than the olds Buicks ect. Smart phones,
So now everyone keeps their cats indoors. ( My wife says it’s none of the above but it must be my poor abilities)
My takeaway is that exercise and muscle mass might be a 25% driver of life span and health span. (In cats). Which is a much closer model organism to humans than mice.
No scientist here by any measure but If I were to guess I’d say other than primates/monkeys I doubt any animals are closer than the rest to us humans. So, my guess would be a cat is nowhere near closer to us than a mouse is, but this is purely a guess. I did however read that pigs organs are nearly indistinguishable from that of humans, maybe that’s why the expression “all men are pigs” LOL
You obviously didn’t read my posts in Rapamycin for Cats
Genetically, we are closer to cats.
The “Gene-Wise” Ranking (Whose DNA looks more like ours?)
If we ignore the timeline and just look at the percentage of homologous genes (genes inherited from a shared ancestor that perform similar functions) that remain intact and similar to ours today, the domestic cat jumps ahead of the rat.
Animal
Homologous Genes Shared with Humans
Evolutionary Branch
Chimpanzee
~98%
Primate (Closest cousin)
Domestic Cat
~90%
Carnivora (Distant cousin)
Dog
~82-85%
Carnivora (Distant cousin)
Cow
~80%
Artiodactyla (Distant cousin)
Lab Rat / Mouse
~75-85%*
Glires (Closer cousin)
*Note: While mice and rats share a high percentage of their base genes with us, their overall chromosomal structure has scrambled significantly more than a cat’s.
Why the Paradox?
The reason for this mismatch between evolutionary time and genetic similarity comes down to mutation rates.
Rodents, like lab rats, are evolutionary speedrunners. They have very fast reproductive cycles and experience an unusually high rate of genetic mutation and chromosomal reshuffling. Over millions of years, their DNA has broken apart and rearranged itself rapidly.
Cats, on the other hand, have incredibly “stable” genomes. The domestic cat’s DNA has experienced very few chromosomal rearrangements since the days of the early mammalian ancestors. Because both humans and cats have relatively slow-mutating, stable genomes, a modern cat’s chromosomal organization (called synteny) looks remarkably similar to a human’s — meaning genes found next to each other on a human chromosome are very often found right next to each other on a feline chromosome, too.
References
The Abyssinian Cat Genome Project (2007): A landmark study published in Genome Research that first sequenced the domestic cat genome, revealing the ~90% homologous gene overlap and the high degree of chromosomal conservation compared to humans.
Mammalian Evolutionary Phylogeny: Genetic sequencing of the superorders Euarchontoglires and Laurasiatheria confirms that primates and rodents share a more recent common ancestor than primates and carnivores do.
Comparative Genomics of Rodentia: Studies on mammalian genome reshuffling (e.g., Oxford Academic, Genome Biology and Evolution) demonstrate that rodents have an exceptionally high rate of chromosomal breakage and rearrangement compared to other mammals.
Wow @Satchel on 25-26! I’ve never met a cat that old.
I lost two but the remaining 3 are 17, 18 and 19 (to think, I thought I was breaking all sorts of records!).
Funny you mentioned coyotes because I just took this 15 minutes ago!
My 17 and 19 year old cats chase coyotes and bobcats through the windows.
It surprises me they don’t seem to have any awareness that they would lose that battle, especially the 3-legged 19 year old who can barely walk anymore… he’ll hobble after them.
If they were outdoor cats, they would not make it to sundown.
Not so fast LOL. Unless that is a picture of a 150lbs wolf, no jackal, nor cayote, nor fox will ever mess with a cat. If it were a small dog that’s a different story.
We have been having but C for about 5 Years, we have not had a cold or flue, in all that time. My Husband got covid but it was just a sniffle and lasted half a day, I didn’t get it off him despite sleeping together , I got it much later and it came on during sleep, it was a strange feeling but it was gone within a few hours. Apart from Vit C we have ozone therapy weekly at home. We played golf on 4 consecutive days last week , no aches or pains
Wow played golf 4 days in one week and you’re over 80? You must definitely be doing something right. Good for you. Out of curiosity, do you get IV infusions of Vit C at a clinic, or you found your away around it and do it at home?
We have an intergrative medicine doctor who does all kinds of IV, Google Dr Kalidas, Orlando. We have IV infusion yes but we sometimes have blood ozone where they take a pint of blood from us then infuse it with ozone and return it to is, amazing for your health , at home we have our own ozone equipment , my husband is a Biologist so he set it up to give ourselves rectal insufflation of ozone, also he has linked our sauna to ozone too .
I have been using Rapamycin for over 2 years at 6mg per week for 3 months, take 1 month off, and repeat for 3 months, etc. I think it has significantly boosted my immune system as I have not been sick since starting this regiment. Started when I was 65 and am 67 now. Play golf 2 time or more per week and walk daily and lift weights every other day. I feel like this has been a game changer for me and appreciate the positive effects I am experiencing.
