Long story short, Joe, the 39-year-old mole rat, is still going strong and having children.
“All mammals, including people, naturally make this protein, but Buffenstein recently found that the naked mole rat version is more active, either because it’s more abundant or better at binding. Drug developers have also noticed that NRF2 is involved in medications approved to treat specific diseases. For example, metformin, a diabetes drug, also activates NRF2 and is being studied for anti-aging. Rapamycin, an immunosuppressant prescribed after organ transplants, activates NRF2 and extends life span by about 25 percent in male and female mice. Clinical trials are underway to test it against human aging. Perhaps NRF2 helps mole rats escape the onset of multiple aging-related diseases simultaneously.”
Here they link Rapamycin and metformin to NRF2. Also, Astaxanthin which the ITP has said is very promising also affects NRF2. Could it be that this is the key to our aging and why Rapa, metformin and ATX work?
Or maybe the secret is the Okinawan diet as Joe loves sweet potatoes…
You’ve got to love the NMR. Lives and thrives in sewer- like conditions.
People have been interested in the benefits of upregulating NRF2 for some time now. Cruciferous vegetables are a good bet, especially broccoli sprouts.
I’m looking into the possibility of broccoli sprouts in powder form.
Seems like NMR live in a dark low oxygen environment. Much like computer programmers…
Broccoli sprouts are the immature version of broccoli, or you are talking about the top part of the full grown broccoli stalk? Why is one better than the other?
The sprouts deliver more sulforaphane. You can grow them yourself but it would be easier to get the powder if it works the same.
As you can imagine, the aging signature is incredibly complex genetically, with a myriad of pathways. The NMR stands out for an enriched set of positively selected genes (PSG’s) for anti-aging, and mTOR is HIGHLY implicated.
FULL STEAM AHEAD!
Long-lived rodents reveal signatures of positive selection in genes associated with lifespan
“To gain new insights into genetic mechanisms determining mammalian lifespans, we obtained genomic and transcriptomic data from 17 rodent species and scanned eleven evolutionary branches associated with the evolution of enhanced longevity for positively selected genes (PSGs). we found the PSGs to be enriched for genes known to be related to aging. Among these enrichments were “cellular respiration” and “metal ion homeostasis”, as well as functional terms associated with processes regulated by the mTOR pathway: translation, autophagy and inflammation. Regulation of mTOR- and downstream processes show signs of positive selection leading to enhanced longevity. Remarkably, among PSGs are RHEB, a regulator of mTOR, and IGF1, both central components of aging-relevant pathways”
"In addition, we recently observed that PSGs in short-lived and fast-growing killifish were significantly more often up- than down-regulated during aging. This finding is consistent with the concept of antagonistic pleiotropy suggesting that the same genes that are positively selected for fast growth and maturation at young age are drivers of aging at old age. The antagonistic pleiotropy hypothesis is well supported, e.g. by the fact that growth rate and lifespan are negatively correlated, both between species and within many species. The result is also consistent with the HYPERFUNCTION THEORY OF AGING that suggests that antagonistic pleiotropy works via a mechanism of “perverted” growth. According to this theory the growth program that is beneficial during youth is not entirely stopped after finishing development and causes damage from that point on.
The theory further claims that the master regulator mTOR (mechanistic target of rapamycin) governs this growth program"
Yeah, the little creatures have built in mTOR inhibition. Like having an IV rapamycin pump. Wonder what would happen if we augmented it with some weekly rapamycin.
Maybe they’d live forever.
I think it’s possible for them to live forever now… Let’s see how long Joe lasts. He’s doing pretty good for being 300 years old in human years…
Get Richard Miller at the ITP to do a study with NMR on rapamcyin…the results would be enlightening either way.
It may take centuries to get results…
Haha, yeah, it might be quicker to do a human study.
Probably, but I would LOVE to see how rapamycin changes the gene expression, especially positively selected genes (PSG’s) in an NMR, even without waiting for the lifespan extension results. What more could they teach us about rapamycin and inter-conected longevity pathways?
Uh, naked mole rats have annual death rates equivalent of that of humans in their 80s each year for their entire lifespans - that’s why barely any NMRs make it beyond age 40, and humans are not that aged by 40.
Naked Mole Rats (NMRs) primarily die from physical trauma, due to their social structure, not old age.
But Buffenstein did not see this trend in her lab animals. After they reached sexual maturity at 6 months of age, each naked mole rat’s daily chance of dying was a little more than one in 10,000. It stayed the same the rest of their lives and even went down a little, Buffenstein reports this week in elife. “To me this is the most exciting data I’ve ever gotten,” says Buffenstein. “It goes against everything we know in terms of mammalian biology.”
If we executed a certain percentage of human males each year, it would change things for us as well.
Joe, the oldest NMR at 41, is as healthy as ever and producing offspring. Maybe he’s the Fabio of the NMR world as he is still favoured by his queen and hasn’t been knocked off yet?
I used to grow my own broccoli sprouts Dr Rhonda Patrick style but it became a bit of a faff after the initial novelty wore off. Plus to be frank smoothies with broccoli sprouts and mustard seeds tastes absolutely foul. Since then I’ve been taking Prostaphane which is a stabilised sulforaphane so you get a better idea of dosing. As I understand it supplements or raw sprouts rely on glucoraphanin being acted upon by the enzyme myrosinase. The efficacy of which I think can vary widely from person to person.
Prostaphane used to only be available in France but vitality pro ship within the UK. Not sure what the deal is with US and rest of the world though.
Can’t say I’ve noticed any huge benefits. Maybe it had some neuro protective properties during my bout of Horners Syndrome but clearly not enough to actually prevent it. It’s $156 for 180 capsules so not wildly expensive. I just wonder if there is any interaction with rapamycin or any synergistic effects.
I have a family history of prostate cancer and there is pretty compelling evidence that sulforaphane slows progression so that’s the main reason I continue to take it.
NMRs epigenetically age faster than humans (see papers from Gladyshev’s lab)
They also acquire oxidative stress damage to their proteins faster than humans. While it is said that oxidative damage to proteins enhances function in NMRs, we don’t know if this continues to be true once they reach ages similar to humans when humans experience significant noticeable functional decline.