13 ms·

Senescent cells stop producing nucleotides: new research

309 points by LinuxBender 7y ago

AstralStorm 7y ago
Is this sloppy reporting or are these researchers actually confused about senescent cells often having two nuclei? One of the known cause of cellular senescence is G-phase cell division cycle arrest, usually due to damage, which will result in a cell with two nuclei...
- debatem1 7y ago
  Is there a good place to learn about this that doesn't assume a deep bio background?
- telotortium 7y ago
  (No biology training here.) According to Wikipedia, it looks like G-phase is part of interphase. During interphase, the cell isn't actually in the process of dividing, right? Wouldn't it be more likely that a senescent cell would have two nuclei if there was an error during telophase, right before cytokinesis?
myarr 7y ago
Sounds like this supports marketing claims by Elysium? https://www.elysiumhealth.com/en-us/basis https://www.elysiumhealth.com/en-us/basis
pkilgore 7y ago
Now granted I only have a undergraduate degree in Chemistry, but to me, the statement "the lack of nucleotides causes cells to age" is akin to saying "the lack of steel causes a car factory to stop". Of course if a cell lacks the basic components to divide its DNA it... won't divide? The more interesting question is _why_ are there no nucleotides in cells that are aging. My sense is that this summary of the underlying article is missing something (not uncommon in scientific journalism), or this really isn't all that revolutionary. I'd love for a better explanation of why this matters, or a better link?
- thebeefytaco 7y ago
  Here's the original article: https://viterbischool.usc.edu/news/2019/07/fighting-back-against-the-ravages-of-time/ https://viterbischool.usc.edu/news/2019/07/fighting-back-aga... And the primary source/study: http://www.jbc.org/content/early/2019/05/28/jbc.RA118.005806 http://www.jbc.org/content/early/2019/05/28/jbc.RA118.005806
  - deleted 7y ago
    [deleted]
  - pkilgore 7y ago
    Thank you.
- heymijo 7y ago
  Excellent line of inquiry. I'll have to dig but I know I've read that senesence has an important function. Like most things in the body, it happens for a reason but there are often downsides. It was probably something Dr. Judith Campesi, a pre eminent senesence scholar, wrote.
  - DenisM 7y ago
    > I've read that senesence has an important function Unless you're a water bear your DNA accrues continuous and irreversible damage throughout life. End of the road is either cancer or senesence as an attempt to arrest cancer.
    - heymijo 7y ago
      Thank you. That was it. Senesence > cancer Edit: Can't believe I forgot the third option, cell death. Here's some info from Dr. Rhonda Patrick and Dr. Judith Campisi when they got together for an interview. > As our cells accumulate damage, which naturally happens as we age (even as a consequence of energy-generating processes and immune cell activation), there are only so many outcomes that we can expect. The first possibility is that the cells can die. The second is that they can become senescent – where they stop dividing, but stay alive, all-the-while secreting molecules that influence surrounding tissue. Or, the worst of all possible outcomes, the cells can go off the rails and become malignant. > "Anything that persistent damage to the genome will drive cells into senescence. It makes sense because that puts you at risk for mutations. Mutation puts you at risk for cancer, so the cells want to shut that damaged cell down." - Dr. Judith Campisi https://www.foundmyfitness.com/episodes/59 https://www.foundmyfitness.com/episodes/59
ergothus 7y ago
> The research team discovered that the aging, senescent cells stopped producing a class of chemicals called nucleotides, which are the building blocks of DNA. When they took young cells and forced them to stop producing nucleotides, they became senescent, or aged. ^ From the article. Yet, when I check the linked journal entry: > Inhibition of nucleotide synthesis promotes replicative senescence of human mammary epithelial cells ^ journal article title, which seems somewhat the reverse of the article claim. > To test whether cellular immortalization would reverse these observations, we expressed telomerase in HMECs. In addition to preventing senescence, telomerase expression maintained metabolic flux from glucose into nucleotide synthesis pathways. Finally, we investigated whether inhibition of nucleotide synthesis in proliferating HMECs is sufficient to induce senescence. ^ From the journal article abstract. This states NONE of the "took young cells and..." claims from the article, but rather the opposite. > Taken together, our results suggest that nucleotide synthesis inhibition plays a causative role in the establishment of replicative senescence in HMECs. Umm...unless I'm missing something, this is literally taking correlation and determining causation. TL;DR: This looks like an exploratory data point in the "how does the telomere clock actually cause senescence in a cell". While this COULD lead to some "new" treatment, vast issues remain, including both "is this the sole cause", "is this actually relevant", and "if this is the Big Cause, what could we do about it anyway?"
- jerf 7y ago
  "Umm...unless I'm missing something, this is literally taking correlation and determining causation." Yes. But when you're in a machine as complex as a cell and trying to figure out how to stop some process, if you can find a correlation, it's at least worth a try to treat that as causation. It's much better than picking a random answer. Where we go wrong is when the game of telephone gets played and the correlation gets locked in as the official causation answer. But technically, "I see a correlation between A and B, therefore I hypothesize that the cause of the correlation is that A causes B" is at least a good first hypothesis. (The moreso when "B causes A" is not plausible for some reason.)
  - ergothus 7y ago
    All true - my complaint here was that the article went from "Here's a correlation that might indicate causation" to "This is the cause". Science journalism, I know, but still, if we don't call it out, will it ever improve? I don't think the study was a bad thing at all (from my limited understanding), but the article was...a poor representation of it.
xwdv 7y ago
So basically, exercise can help slow the aging of cells in humans through adaption to stress.
0815test 7y ago
A "new cause of cell aging" might cause trouble for the somewhat-speculative programme of SENS, the pursuit of long-term "negligible" senescence via regenerative medicine. In this case, if it turns out that telomerase is needed to prevent cellular senescence, it seems you can't use whole-body inhibition of telomerase as a cure for cancer, which is the approach SENS is proposing. It doesn't make all regenerative medicine useless, but it might be a challenge.
oppositelock 7y ago
This was the most interesting part to me: "Scott Fraser and his lab worked with the research team to develop 3D imagery of the results. The images unexpectedly revealed that senescent cells often have two nuclei, and that they do not synthesize DNA." Huh, the interesting part to me was that the senescent cells have two nuclei. Muscle cells fuse during development and have multiple nuclei, and they can't divide anymore either. I wonder if senescence happens due to mitosis being stopped short by some mechanism, and whether the multiple nuclei are a symptom or one mechanism by which cells enter senescence.
- gnode 7y ago
  It sounds to me like these senescent cells have reached or completed telophase (construction of nuclear membranes after mitosis), yet cytokinesis (splitting of the cell) has been inhibited. Perhaps during mitosis some kind of genetic integrity check is performed and failure halts cytokinesis (or success enables it).
- echelon 7y ago
  You don't want certain cells to continue to proliferate. The development lifecycle also ends once a cell has differentiated into its ultimate tissue type. You don't want everything to be forever pluripotent. Proliferation and pluripotency are classic markers for cancer.
tjpaudio 7y ago
Well, until it has been confirmed by a study, it's not science, obvious or not. A few years ago there was a major study that proved a relationship between multiple concussions and long term brain damage. Anyone could have made the conclusion that repeated blows to the head is bad but it doesn't become science until we apply rigor to test it. That's a good thing. At all points in history we believed foolish things that we thought were obvious.
- not_a_cop75 7y ago
  And sometimes with modern p-hacking and big corp sponsored studies, it's still not technically science. We should all be wary of the "this one study proves everything" attitude. Confirmation studies are both underfunded and the real rubber meets the road science.
  - misterprime 7y ago
    I'd really love to see an awareness campaign about this issue.
    - OnACoffeeBreak 7y ago
      From my non-scientist perspective who reads things like HN and a few other sources of announce, there's quite a bit of awareness on scientists' part with respect to p hacking. That may not necessarily translate to studies that rely on p hacking to be published and then conferred by the media, though.
    - jimbokun 7y ago
      "Friends don't let friends P-hack." "This is your research on P-hacking." "Just say no to P-hacking!"
      - hundreddaysoff 7y ago
        Ha. The sad reality in our system is that if you choose science as a career, you publish or you perish. P-hacking allows you to publish. Most biologists know they need to publish or perish, but very few know what P-hacking is, although many of them do it implicitly. Once you are aware of the problem, you have three choices that I could see: (1) roll the dice and legitimately win the lottery of objective truth discovery, (2) consciously be evil in order to feed your family, or (3) escape and go find another flawed system to feed yourself. So I chose (3) and went to med school.
hellofunk 7y ago
It would be great to know if there were obvious lifestyle or diet changes that can help the natural mechanisms at work in possibly removing these cells.
- sappapp 7y ago
  It’s hypothesized that intermittent fasting is a natural mechanism. This article is a good introduction: https://lifeapps.io/fasting/a-beginners-guide-to-intermittent-fasting/ https://lifeapps.io/fasting/a-beginners-guide-to-intermitten...
  - jandrese 7y ago
    I would warn that the studies on that are still preliminary. Even really promising research, like the Vitamin D supplement craze from a couple of years ago, can fizzle out when more data comes in.
- asdf21 7y ago
  There are... autophagy. Cannibalizes any under-performing cells.
  - gnode 7y ago
    Autophagy is the self-cannibalisation of cells to give up their molecular components. Are senescent cells capable of doing this? They have at least stopped producing nucleotides, and the double nucleus suggests they have broken down toward the end of mitosis.
    - LinuxBender 7y ago
      Senescent cells can be cannibalized by others. One method involves a feedback system in NRF2 via the modulation of p62. NRF2 activates the expression of many autophagy genes, such as Atg3, Atg5, Atg7 and SQSTM1 during cellular stress response. One component I have been self experimenting with to induce the up-regulation of NRF2 is Sulforaphane. Thus far I have removed cells in my body that were causing eczema. Disclaimer: I am not a scientist and nobody should self experiment. I simply reached a dead end with doctors and won't accept "nothing can be done" as a valid answer.
rrwright 7y ago
"This means that the production of nucleotides is essential to keep cells young," Delfarah said. "It also means that if we could prevent cells from losing nucleotide synthesis, the cells might age more slowly." Am I the only one wondering if this person is confusing cause and effect?
- dumbfoundded 7y ago
  It probably isn't the root cause but it probably isn't the final symptom either. Solving aging seems to resemble working up a complicated tree of causality with multiple roots. Fixing nucleotide synthesis won't make us immortal but it may prevent significant downstream impacts.
- cma 7y ago
  Don't confuse might for definitely
- cgiles 7y ago
  > Am I the only one wondering if this person is confusing cause and effect? No you are not. I work in this field and confusions of cause and effect are a daily occurrence. It is as dumfoundedd said, the reality is that aging is a complex causal network. I think everyone knows that but can't resist the temptation to pretend like the one edge they are working on in the network is the end-all. It can get very ridiculous. At this year's aging meeting someone was actually proposing DNN predictions of age based on people's faces as a gold standard for biomarkers of aging. That is, they were suggesting people's faces were a better indicator of their internal biological state of aging than both their actual age and any internal biological marker. Metagenomics is another one, although more debatable. I personally find it much more plausible that changes in the aging gut cause changes in the microbiome than the reverse (in general). Horvath's epigenetic clock is another one, he presented a elastic net model that could predict age based on DNA methylation using a few hundred loci. For several years and even now, way too many investigators thought those loci were actually causal in aging because they don't understand how statistics work. It annoys me. I have long considered writing a review to remind people what causality means. It is far too common for people to observe correlations and just straight to predicting causality without any additional evidence besides the correlation. The interesting finding of this paper is that inhibition of nucleotide synthesis can induce senescence. But the (simplistic) definition of senescence is inability to replicate. You can't replicate without nucleotides, but this doesn't at all mean that the ordinary cause of senescence is lack of nucleotides. The common understanding is that it is G1 or G2 arrest due to DNA damage of one sort or another. Furthermore, the observation that senescent cells don't produce many nucleotides is kind of a duh. It is useful and important that they quantified it, but still it is hardly surprising. But there is still hope. I just saw my chair in the hall, told him about this paper, and asked his opinion of the idea that "fixing nucleotide synthesis may help reduce cell senescence or help cells age more slowly". His response was to laugh, pat me on the shoulder, and walk away, if that says anything.
holoduke 7y ago
What would happen if there was somekind of treatment where people could reduce aging process, so potentially we could reach the age of 500. Would we still able to handle this mentally wise.
- nkozyra 7y ago
  I don't think most people have the mental energy for our current lifespans
- allworknoplay 7y ago
  There's a whole world of thought on this. Check out some of Aubrey de Grey's work for starters.
  - LinuxBender 7y ago
    In addition to Aubrey, also Dr. David Sinclair.
    - vibrio 7y ago
      ...and GSK who payed >$700 MM for Sinclair's company Sirtris (and closed it 5 years later.)
- krferriter 7y ago
  I think we could easily handle it. Most people want to live longer and do more while they're alive. People who parrot the idea of "the shortness of life is what gives it meaning" are lying to themselves and others, in my view. They use that sort of justification as a coping mechanism, it isn't a truly held belief. If it turned out that humans could now live to 500, they'd just update their baselines to be 500 instead of 80 and adjust to the new situation rapidly.
- mr_toad 7y ago
  > What would happen if there was somekind of treatment where people could reduce aging process Probably the first result would be cancer.
pochamago 7y ago
Are Senolytic drugs something new they came up with our something that we've had for a while?
- crimsonalucard 7y ago
  I've talked to researchers in the bio field dealing with immortal cells. Those cells are apparently dangerous to touch because they will give you cancer.
  - deleted 7y ago
    [deleted]
- gnode 7y ago
  The wikipedia article ( https://en.wikipedia.org/wiki/Senolytic https://en.wikipedia.org/wiki/Senolytic ) cites https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748967/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748967/ from December 2015, so the concept is at least that old.
- hundreddaysoff 7y ago
  My remembrance is that Campisi and others were thinking about them since at least the early 2000s.
beefman 7y ago
As is often the case, simply reading the abstract gives a much better idea of what happened http://www.jbc.org/content/294/27/10564 http://www.jbc.org/content/294/27/10564 It's also faster and easier. It's faster because it's shorter (2k vs 5k). It's easier because 'abstract format' is a tigher constraint than 'popular science story format'. (Much as Wikipedia entries are often easier than random web pages because they're constrained to a standard format.)
- sfink 7y ago
  Whoa! Thanks for this. The abstract makes so much more sense, and is at the same time more exciting, than the originally posted article. That article was like saying that geriatric people are observed to never go clubbing, and if you prevent young people from clubbing they mope around the house all day, so maybe if we get people to go clubbing every day they'll never grow old. The abstract is a lot more reasonable and sensible, and concludes that (lack of) nucleotide synthesis does seem to play an important role in senescence. They were able to kick things back into action with telomerase. Enforced clubbing resources bed sores. No word yet on how many additional injuries it might trigger from ill-advised breakdancing.
dekhn 7y ago
To the computer hackers who read these things: biology is a complex system. So complex that the most complicated system you have ever worked on seems very simple compared to it. WHen you read articles like this, be aware the scientists have extensive training in working with complex systems, and publish exciting sounding coherent narratives that are, at best, incorrect but useful working models (https://en.wikipedia.org/wiki/Not_even_wrong https://en.wikipedia.org/wiki/Not_even_wrong). It's fun to speculate but to prove your case and make a real dent in human health problems is a lot harder than coming in late and saying "But wait, why don't you just..." I heartily recommend going back to the great textbooks of these fields and reading them, rather than trying to understand things by dropping into the state of the art research (which is usually wrong, and hard to understand in detail). Some books I recommend: The Biology of Cancer (Weinberg). After you read this book you'll have a better understanding of why doctors and scientists cringe when people say "cure cancer". Molecular Biology the Cell (Alberts, etc). After you read this book you'll have a much better understanding of the full complexity that scientists have to deal with in complex cellular systems. Molecular Biology of the Gene (watson, etc). Can't say much about this book except that's it's a classic reference. What makes these three books exception is that they support all their factual claims with direct links to the papers that established the facts. And they provide you with the skills to evaluate modern research. But nothing compares to actually going to grad school and participating in the research- once you see how the grants are made, the experiments are, and the papers are written, you'll understand why trying to understand biology by press release is like trying to understand assembly language by watching a Steve Jobs product announcement.
- cgiles 7y ago
  This is not bad advice, especially for people lacking the fundamentals, but these books are often way out of date and only cover topics that have been solidly established 20 years ago. I would suggest, especially for people interested in a relatively niche field like aging, that a good compromise is to read review articles. You can go to PubMed and filter by review articles to find them. But I wholeheartedly concur that for non-experts to read primary research articles will cause much more confusion than clarity. And doubly so for press releases on those articles.

309 points by LinuxBender 7y ago

Is this sloppy reporting or are these researchers actually confused about senescent cells often having two nuclei? One of the known cause of cellular senescence is G-phase cell division cycle arrest, usually due to damage, which will result in a cell with two nuclei...

debatem1 7y ago
Is there a good place to learn about this that doesn't assume a deep bio background?
telotortium 7y ago
(No biology training here.) According to Wikipedia, it looks like G-phase is part of interphase. During interphase, the cell isn't actually in the process of dividing, right? Wouldn't it be more likely that a senescent cell would have two nuclei if there was an error during telophase, right before cytokinesis?

myarr 7y ago

Sounds like this supports marketing claims by Elysium? https://www.elysiumhealth.com/en-us/basis https://www.elysiumhealth.com/en-us/basis

pkilgore 7y ago

Now granted I only have a undergraduate degree in Chemistry, but to me, the statement "the lack of nucleotides causes cells to age" is akin to saying "the lack of steel causes a car factory to stop". Of course if a cell lacks the basic components to divide its DNA it... won't divide? The more interesting question is _why_ are there no nucleotides in cells that are aging. My sense is that this summary of the underlying article is missing something (not uncommon in scientific journalism), or this really isn't all that revolutionary. I'd love for a better explanation of why this matters, or a better link?

thebeefytaco 7y ago
Here's the original article: https://viterbischool.usc.edu/news/2019/07/fighting-back-against-the-ravages-of-time/ https://viterbischool.usc.edu/news/2019/07/fighting-back-aga... And the primary source/study: http://www.jbc.org/content/early/2019/05/28/jbc.RA118.005806 http://www.jbc.org/content/early/2019/05/28/jbc.RA118.005806
- deleted 7y ago
  [deleted]
- pkilgore 7y ago
  Thank you.
heymijo 7y ago
Excellent line of inquiry. I'll have to dig but I know I've read that senesence has an important function. Like most things in the body, it happens for a reason but there are often downsides. It was probably something Dr. Judith Campesi, a pre eminent senesence scholar, wrote.
- DenisM 7y ago
  > I've read that senesence has an important function Unless you're a water bear your DNA accrues continuous and irreversible damage throughout life. End of the road is either cancer or senesence as an attempt to arrest cancer.
  - heymijo 7y ago
    Thank you. That was it. Senesence > cancer Edit: Can't believe I forgot the third option, cell death. Here's some info from Dr. Rhonda Patrick and Dr. Judith Campisi when they got together for an interview. > As our cells accumulate damage, which naturally happens as we age (even as a consequence of energy-generating processes and immune cell activation), there are only so many outcomes that we can expect. The first possibility is that the cells can die. The second is that they can become senescent – where they stop dividing, but stay alive, all-the-while secreting molecules that influence surrounding tissue. Or, the worst of all possible outcomes, the cells can go off the rails and become malignant. > "Anything that persistent damage to the genome will drive cells into senescence. It makes sense because that puts you at risk for mutations. Mutation puts you at risk for cancer, so the cells want to shut that damaged cell down." - Dr. Judith Campisi https://www.foundmyfitness.com/episodes/59 https://www.foundmyfitness.com/episodes/59

ergothus 7y ago

> The research team discovered that the aging, senescent cells stopped producing a class of chemicals called nucleotides, which are the building blocks of DNA. When they took young cells and forced them to stop producing nucleotides, they became senescent, or aged. ^ From the article. Yet, when I check the linked journal entry: > Inhibition of nucleotide synthesis promotes replicative senescence of human mammary epithelial cells ^ journal article title, which seems somewhat the reverse of the article claim. > To test whether cellular immortalization would reverse these observations, we expressed telomerase in HMECs. In addition to preventing senescence, telomerase expression maintained metabolic flux from glucose into nucleotide synthesis pathways. Finally, we investigated whether inhibition of nucleotide synthesis in proliferating HMECs is sufficient to induce senescence. ^ From the journal article abstract. This states NONE of the "took young cells and..." claims from the article, but rather the opposite. > Taken together, our results suggest that nucleotide synthesis inhibition plays a causative role in the establishment of replicative senescence in HMECs. Umm...unless I'm missing something, this is literally taking correlation and determining causation. TL;DR: This looks like an exploratory data point in the "how does the telomere clock actually cause senescence in a cell". While this COULD lead to some "new" treatment, vast issues remain, including both "is this the sole cause", "is this actually relevant", and "if this is the Big Cause, what could we do about it anyway?"

jerf 7y ago
"Umm...unless I'm missing something, this is literally taking correlation and determining causation." Yes. But when you're in a machine as complex as a cell and trying to figure out how to stop some process, if you can find a correlation, it's at least worth a try to treat that as causation. It's much better than picking a random answer. Where we go wrong is when the game of telephone gets played and the correlation gets locked in as the official causation answer. But technically, "I see a correlation between A and B, therefore I hypothesize that the cause of the correlation is that A causes B" is at least a good first hypothesis. (The moreso when "B causes A" is not plausible for some reason.)
- ergothus 7y ago
  All true - my complaint here was that the article went from "Here's a correlation that might indicate causation" to "This is the cause". Science journalism, I know, but still, if we don't call it out, will it ever improve? I don't think the study was a bad thing at all (from my limited understanding), but the article was...a poor representation of it.

xwdv 7y ago

So basically, exercise can help slow the aging of cells in humans through adaption to stress.

0815test 7y ago

A "new cause of cell aging" might cause trouble for the somewhat-speculative programme of SENS, the pursuit of long-term "negligible" senescence via regenerative medicine. In this case, if it turns out that telomerase is needed to prevent cellular senescence, it seems you can't use whole-body inhibition of telomerase as a cure for cancer, which is the approach SENS is proposing. It doesn't make all regenerative medicine useless, but it might be a challenge.

oppositelock 7y ago

This was the most interesting part to me: "Scott Fraser and his lab worked with the research team to develop 3D imagery of the results. The images unexpectedly revealed that senescent cells often have two nuclei, and that they do not synthesize DNA." Huh, the interesting part to me was that the senescent cells have two nuclei. Muscle cells fuse during development and have multiple nuclei, and they can't divide anymore either. I wonder if senescence happens due to mitosis being stopped short by some mechanism, and whether the multiple nuclei are a symptom or one mechanism by which cells enter senescence.

gnode 7y ago
It sounds to me like these senescent cells have reached or completed telophase (construction of nuclear membranes after mitosis), yet cytokinesis (splitting of the cell) has been inhibited. Perhaps during mitosis some kind of genetic integrity check is performed and failure halts cytokinesis (or success enables it).
echelon 7y ago
You don't want certain cells to continue to proliferate. The development lifecycle also ends once a cell has differentiated into its ultimate tissue type. You don't want everything to be forever pluripotent. Proliferation and pluripotency are classic markers for cancer.

tjpaudio 7y ago

Well, until it has been confirmed by a study, it's not science, obvious or not. A few years ago there was a major study that proved a relationship between multiple concussions and long term brain damage. Anyone could have made the conclusion that repeated blows to the head is bad but it doesn't become science until we apply rigor to test it. That's a good thing. At all points in history we believed foolish things that we thought were obvious.

not_a_cop75 7y ago
And sometimes with modern p-hacking and big corp sponsored studies, it's still not technically science. We should all be wary of the "this one study proves everything" attitude. Confirmation studies are both underfunded and the real rubber meets the road science.
- misterprime 7y ago
  I'd really love to see an awareness campaign about this issue.
  - OnACoffeeBreak 7y ago
    From my non-scientist perspective who reads things like HN and a few other sources of announce, there's quite a bit of awareness on scientists' part with respect to p hacking. That may not necessarily translate to studies that rely on p hacking to be published and then conferred by the media, though.
  - jimbokun 7y ago
    "Friends don't let friends P-hack." "This is your research on P-hacking." "Just say no to P-hacking!"
    - hundreddaysoff 7y ago
      Ha. The sad reality in our system is that if you choose science as a career, you publish or you perish. P-hacking allows you to publish. Most biologists know they need to publish or perish, but very few know what P-hacking is, although many of them do it implicitly. Once you are aware of the problem, you have three choices that I could see: (1) roll the dice and legitimately win the lottery of objective truth discovery, (2) consciously be evil in order to feed your family, or (3) escape and go find another flawed system to feed yourself. So I chose (3) and went to med school.

hellofunk 7y ago

It would be great to know if there were obvious lifestyle or diet changes that can help the natural mechanisms at work in possibly removing these cells.

sappapp 7y ago
It’s hypothesized that intermittent fasting is a natural mechanism. This article is a good introduction: https://lifeapps.io/fasting/a-beginners-guide-to-intermittent-fasting/ https://lifeapps.io/fasting/a-beginners-guide-to-intermitten...
- jandrese 7y ago
  I would warn that the studies on that are still preliminary. Even really promising research, like the Vitamin D supplement craze from a couple of years ago, can fizzle out when more data comes in.
asdf21 7y ago
There are... autophagy. Cannibalizes any under-performing cells.
- gnode 7y ago
  Autophagy is the self-cannibalisation of cells to give up their molecular components. Are senescent cells capable of doing this? They have at least stopped producing nucleotides, and the double nucleus suggests they have broken down toward the end of mitosis.
  - LinuxBender 7y ago
    Senescent cells can be cannibalized by others. One method involves a feedback system in NRF2 via the modulation of p62. NRF2 activates the expression of many autophagy genes, such as Atg3, Atg5, Atg7 and SQSTM1 during cellular stress response. One component I have been self experimenting with to induce the up-regulation of NRF2 is Sulforaphane. Thus far I have removed cells in my body that were causing eczema. Disclaimer: I am not a scientist and nobody should self experiment. I simply reached a dead end with doctors and won't accept "nothing can be done" as a valid answer.

rrwright 7y ago

"This means that the production of nucleotides is essential to keep cells young," Delfarah said. "It also means that if we could prevent cells from losing nucleotide synthesis, the cells might age more slowly." Am I the only one wondering if this person is confusing cause and effect?

dumbfoundded 7y ago
It probably isn't the root cause but it probably isn't the final symptom either. Solving aging seems to resemble working up a complicated tree of causality with multiple roots. Fixing nucleotide synthesis won't make us immortal but it may prevent significant downstream impacts.
cma 7y ago
Don't confuse might for definitely
cgiles 7y ago
> Am I the only one wondering if this person is confusing cause and effect? No you are not. I work in this field and confusions of cause and effect are a daily occurrence. It is as dumfoundedd said, the reality is that aging is a complex causal network. I think everyone knows that but can't resist the temptation to pretend like the one edge they are working on in the network is the end-all. It can get very ridiculous. At this year's aging meeting someone was actually proposing DNN predictions of age based on people's faces as a gold standard for biomarkers of aging. That is, they were suggesting people's faces were a better indicator of their internal biological state of aging than both their actual age and any internal biological marker. Metagenomics is another one, although more debatable. I personally find it much more plausible that changes in the aging gut cause changes in the microbiome than the reverse (in general). Horvath's epigenetic clock is another one, he presented a elastic net model that could predict age based on DNA methylation using a few hundred loci. For several years and even now, way too many investigators thought those loci were actually causal in aging because they don't understand how statistics work. It annoys me. I have long considered writing a review to remind people what causality means. It is far too common for people to observe correlations and just straight to predicting causality without any additional evidence besides the correlation. The interesting finding of this paper is that inhibition of nucleotide synthesis can induce senescence. But the (simplistic) definition of senescence is inability to replicate. You can't replicate without nucleotides, but this doesn't at all mean that the ordinary cause of senescence is lack of nucleotides. The common understanding is that it is G1 or G2 arrest due to DNA damage of one sort or another. Furthermore, the observation that senescent cells don't produce many nucleotides is kind of a duh. It is useful and important that they quantified it, but still it is hardly surprising. But there is still hope. I just saw my chair in the hall, told him about this paper, and asked his opinion of the idea that "fixing nucleotide synthesis may help reduce cell senescence or help cells age more slowly". His response was to laugh, pat me on the shoulder, and walk away, if that says anything.

holoduke 7y ago

What would happen if there was somekind of treatment where people could reduce aging process, so potentially we could reach the age of 500. Would we still able to handle this mentally wise.

nkozyra 7y ago
I don't think most people have the mental energy for our current lifespans
allworknoplay 7y ago
There's a whole world of thought on this. Check out some of Aubrey de Grey's work for starters.
- LinuxBender 7y ago
  In addition to Aubrey, also Dr. David Sinclair.
  - vibrio 7y ago
    ...and GSK who payed >$700 MM for Sinclair's company Sirtris (and closed it 5 years later.)
krferriter 7y ago
I think we could easily handle it. Most people want to live longer and do more while they're alive. People who parrot the idea of "the shortness of life is what gives it meaning" are lying to themselves and others, in my view. They use that sort of justification as a coping mechanism, it isn't a truly held belief. If it turned out that humans could now live to 500, they'd just update their baselines to be 500 instead of 80 and adjust to the new situation rapidly.
mr_toad 7y ago
> What would happen if there was somekind of treatment where people could reduce aging process Probably the first result would be cancer.

pochamago 7y ago

Are Senolytic drugs something new they came up with our something that we've had for a while?

crimsonalucard 7y ago
I've talked to researchers in the bio field dealing with immortal cells. Those cells are apparently dangerous to touch because they will give you cancer.
- deleted 7y ago
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gnode 7y ago
The wikipedia article ( https://en.wikipedia.org/wiki/Senolytic https://en.wikipedia.org/wiki/Senolytic ) cites https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748967/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748967/ from December 2015, so the concept is at least that old.
hundreddaysoff 7y ago
My remembrance is that Campisi and others were thinking about them since at least the early 2000s.

beefman 7y ago

As is often the case, simply reading the abstract gives a much better idea of what happened http://www.jbc.org/content/294/27/10564 http://www.jbc.org/content/294/27/10564 It's also faster and easier. It's faster because it's shorter (2k vs 5k). It's easier because 'abstract format' is a tigher constraint than 'popular science story format'. (Much as Wikipedia entries are often easier than random web pages because they're constrained to a standard format.)

sfink 7y ago
Whoa! Thanks for this. The abstract makes so much more sense, and is at the same time more exciting, than the originally posted article. That article was like saying that geriatric people are observed to never go clubbing, and if you prevent young people from clubbing they mope around the house all day, so maybe if we get people to go clubbing every day they'll never grow old. The abstract is a lot more reasonable and sensible, and concludes that (lack of) nucleotide synthesis does seem to play an important role in senescence. They were able to kick things back into action with telomerase. Enforced clubbing resources bed sores. No word yet on how many additional injuries it might trigger from ill-advised breakdancing.

dekhn 7y ago

To the computer hackers who read these things: biology is a complex system. So complex that the most complicated system you have ever worked on seems very simple compared to it. WHen you read articles like this, be aware the scientists have extensive training in working with complex systems, and publish exciting sounding coherent narratives that are, at best, incorrect but useful working models (https://en.wikipedia.org/wiki/Not_even_wrong https://en.wikipedia.org/wiki/Not_even_wrong). It's fun to speculate but to prove your case and make a real dent in human health problems is a lot harder than coming in late and saying "But wait, why don't you just..." I heartily recommend going back to the great textbooks of these fields and reading them, rather than trying to understand things by dropping into the state of the art research (which is usually wrong, and hard to understand in detail). Some books I recommend: The Biology of Cancer (Weinberg). After you read this book you'll have a better understanding of why doctors and scientists cringe when people say "cure cancer". Molecular Biology the Cell (Alberts, etc). After you read this book you'll have a much better understanding of the full complexity that scientists have to deal with in complex cellular systems. Molecular Biology of the Gene (watson, etc). Can't say much about this book except that's it's a classic reference. What makes these three books exception is that they support all their factual claims with direct links to the papers that established the facts. And they provide you with the skills to evaluate modern research. But nothing compares to actually going to grad school and participating in the research- once you see how the grants are made, the experiments are, and the papers are written, you'll understand why trying to understand biology by press release is like trying to understand assembly language by watching a Steve Jobs product announcement.

cgiles 7y ago
This is not bad advice, especially for people lacking the fundamentals, but these books are often way out of date and only cover topics that have been solidly established 20 years ago. I would suggest, especially for people interested in a relatively niche field like aging, that a good compromise is to read review articles. You can go to PubMed and filter by review articles to find them. But I wholeheartedly concur that for non-experts to read primary research articles will cause much more confusion than clarity. And doubly so for press releases on those articles.