This is a candidate-gene study: a single gene in a single population without replication. Previous candidate-gene studies on other traits have replication rates as low or lower than 1% despite apparently dramatic effect sizes - GWASes they definitely are not! I'll believe this mutation when I see it replicated somewhere else.
Wow. We thought the Amish were just getting lots of healthy exercise, but it turns out they’re the genetic Knights Templar, guarding a secret source of life for hundreds of years. Of course, their lifestyle probably maintains the healthiest gut flora around as well.
The Amish love sugar as much as the next group along. Jams, jellies, preserves; pies, cakes, and cookies are all part of their diet.
They are probably less likely to consume large amounts of prepackaged desserts, sodas and snack foods than their "English" neighbors, but that varies from community to community.
But they do! I have a sweet tooth and some of their stuff is just too sweet for me. It really depends on what part of the country they are in, but Pennsylvania Amish are known for their pies. One of the most famous types, Shoofly Pie, is basically sugar flavored sugar.
You’d be wrong to assume it. Amish make some of the best candies around, made the old way but full of sugar. I doubt they are growing their own sugar cane so it’s likely it comes from sugar beets or corn.
My fried growing up was from Pennsylvania and would bring back massive amounts of candy from Amish country. Whenever I drive to Florida I see many road side stores touting “Amish made candy”.
The answer is yes they eat the candy they make as well.
And of course there are human loss of function myostatin mutants, but I can never find the articles I recall reading years back on some of the few known individuals.
From what I understand the Amish diet and lifestyle doesn't map well to mainstream America. To attribute their success (so to speak) to genes strikes me as flawed.
If nothing else, this is a case for epigenetics. But to promote that you are your genes, nothing more and nothing less, feels irresponsible, at best.
Find a diabetes cure and be a the world's first trillionaire and probably go directly to heaven when time comes :) ?
>>The total cost of diabetes and prediabetes in the U.S. is $322 billion.
- The average price of insulin increased nearly 3 times between 2002 and 2013.
- People with diabetes have health care costs 2.3 times greater than those without diabeteshttp://www.diabetes.org/diabetes-basics/statistics/infograph...
Researchers have found a noteworthy effect on longevity in a small study population that includes the only known individuals with a loss of function mutation in plasminogen activator inhibitor-1 (PAI-1). Individuals with the mutation live seven years longer on average than near relatives without it. Repeating the study with larger groups of people obviously isn't a practical option in the case of rare mutations - we're stuck with the family trees that the research community is fortunate enough to identify - but one nonetheless has to wish for more individuals, in order to obtain a more reliable confirmation, when an effect of this size is reported. It means taking a step back to revisit questions we've asked ourselves about the odds of finding significant longevity-enhancing mutations in our species, based upon the absence of results for the past twenty years of searching.
This is also a finding that can and probably should be taken as support for current work on elimination of senescent cells as a potential rejuvenation therapy. PAI-1 isn't a gene pulled from thin air in this context. It is well studied for its influence on aging, and appears to be one of the driving regulators of the harmful effects of cellular senescence. Lingering senescent cells accumulate with age, and secrete a mix of damaging signal molecules that produce chronic inflammation, damage tissue structure, and alter the behavior of nearby cells for the worse. This is known as the senescence-associated secretory phenotype (SASP), and PAI-1 is involved in both the SASP and in some of the processes by which cells become senescent. Studies show that inhibition or loss of PAI-1 reduces some of the harms now known to be associated with senescent cell presence, and in doing so slows measures of aging.
There is all sorts of past research into PAI-1 and senescent cells that we might choose to draw lines between. To pick one example, PAI-1 inhibition can slow atherosclerosis, just as can removal of senescent foam cells in atherosclerotic plaque. There are no doubt overlapping mechanisms here, though it seems clear that reducing PAI-1 levels has a variety of other effects as well. Those effects can't be all that terrible given the existence of a lineage of thriving human mutants lacking PAI-1, something that is always a good demonstration to have in hand. There are a few other beneficial mutations with a small human population to examine, such as those related to reduced blood lipids or myostatin loss of function; we may see many of these lines of research result in therapies in the years ahead.
And yet! While there will no doubt be an avalanche of funding into bringing PAI-1 inhibitors to the clinic, ask yourself this: if tinkering with a fraction of the harmful secretions of senescent cells is this beneficial, how much better will it be to remove these damaging cells entirely via senolytic therapies? All of those involved in this field should spend more time than they do on work with a higher expectation value, I believe.
There are two things that make this question very difficult to answer.
The first is that our genetic code is spaghetti code beyond the dreams of the most cowboy of the 70's cowboy assembly programmers. Our genes and proteins are reused in different ways at different times in different cells in ways that make it difficult to unequivocally call a gene "good" or "bad".
The second is that even evaluating along the simple "does it make things survive and reproduce better?" evolutionary metric, you still need to consider the exact, current environment a gene is being evaluated in; a gene can be harmful today and beneficial yesterday, or vice versa. Maybe the gene confers an immunity to a virulent, deadly, extinct disease; maybe it was necessary when another gene was present, a gene which has since changed.
Evolution isn't particularly fast, most of the time; any given organism will be adapted to a smear of their environments as they existed over the last few million years, and not perfectly adapted to any of them (unless their environment has remained static).
I believe it. Have you ever eaten a meal with the Amish? I have. They love sugar and put it in everything. And they eat substantial meals because many of the men are engaged in physical work. I got a distinct buzz, and that was before dessert was served!
This is the first time I've read about a clotting disorder being beneficial for heterozygotes besides sickle cell. I'm curious if other types of these disorders show the same effect (I am a carrier of one myself).
[+] [-] gwern|8 years ago|reply
[+] [-] zach|8 years ago|reply
[+] [-] hueving|8 years ago|reply
Is there any science behind that statement or is it just a sort of naturalistic fallacy?
[+] [-] dialtones|8 years ago|reply
[deleted]
[+] [-] Dowwie|8 years ago|reply
[+] [-] dsr_|8 years ago|reply
They are probably less likely to consume large amounts of prepackaged desserts, sodas and snack foods than their "English" neighbors, but that varies from community to community.
[+] [-] mamoswined|8 years ago|reply
[+] [-] pbnjay|8 years ago|reply
[+] [-] megaman22|8 years ago|reply
[+] [-] wil421|8 years ago|reply
My fried growing up was from Pennsylvania and would bring back massive amounts of candy from Amish country. Whenever I drive to Florida I see many road side stores touting “Amish made candy”.
The answer is yes they eat the candy they make as well.
[+] [-] tyingq|8 years ago|reply
[+] [-] greggarious|8 years ago|reply
My dad used to buy chocolate chip cookies and gobs[1] from the Amish at the farmer's market. They were huge, and good but definitely not healthy :)
https://en.wikipedia.org/wiki/Whoopie_pie
[+] [-] kwhitefoot|8 years ago|reply
[+] [-] jandrese|8 years ago|reply
[+] [-] sanxiyn|8 years ago|reply
[+] [-] reasonattlm|8 years ago|reply
ANGPTL4: http://www.tum.de/en/about-tum/news/press-releases/short/art...
ASGR1: http://healthsciences.ku.dk/news/new-2016/mutation-protects-...
Growth hormone receptor: http://www.nbcnews.com/health/aging/little-people-ecuador-la...
And of course there are human loss of function myostatin mutants, but I can never find the articles I recall reading years back on some of the few known individuals.
[+] [-] chiefalchemist|8 years ago|reply
If nothing else, this is a case for epigenetics. But to promote that you are your genes, nothing more and nothing less, feels irresponsible, at best.
[+] [-] tryingagainbro|8 years ago|reply
>>The total cost of diabetes and prediabetes in the U.S. is $322 billion. - The average price of insulin increased nearly 3 times between 2002 and 2013. - People with diabetes have health care costs 2.3 times greater than those without diabetes http://www.diabetes.org/diabetes-basics/statistics/infograph...
[+] [-] reasonattlm|8 years ago|reply
Paper: https://doi.org/10.1126/sciadv.aao1617
Researchers have found a noteworthy effect on longevity in a small study population that includes the only known individuals with a loss of function mutation in plasminogen activator inhibitor-1 (PAI-1). Individuals with the mutation live seven years longer on average than near relatives without it. Repeating the study with larger groups of people obviously isn't a practical option in the case of rare mutations - we're stuck with the family trees that the research community is fortunate enough to identify - but one nonetheless has to wish for more individuals, in order to obtain a more reliable confirmation, when an effect of this size is reported. It means taking a step back to revisit questions we've asked ourselves about the odds of finding significant longevity-enhancing mutations in our species, based upon the absence of results for the past twenty years of searching.
This is also a finding that can and probably should be taken as support for current work on elimination of senescent cells as a potential rejuvenation therapy. PAI-1 isn't a gene pulled from thin air in this context. It is well studied for its influence on aging, and appears to be one of the driving regulators of the harmful effects of cellular senescence. Lingering senescent cells accumulate with age, and secrete a mix of damaging signal molecules that produce chronic inflammation, damage tissue structure, and alter the behavior of nearby cells for the worse. This is known as the senescence-associated secretory phenotype (SASP), and PAI-1 is involved in both the SASP and in some of the processes by which cells become senescent. Studies show that inhibition or loss of PAI-1 reduces some of the harms now known to be associated with senescent cell presence, and in doing so slows measures of aging.
There is all sorts of past research into PAI-1 and senescent cells that we might choose to draw lines between. To pick one example, PAI-1 inhibition can slow atherosclerosis, just as can removal of senescent foam cells in atherosclerotic plaque. There are no doubt overlapping mechanisms here, though it seems clear that reducing PAI-1 levels has a variety of other effects as well. Those effects can't be all that terrible given the existence of a lineage of thriving human mutants lacking PAI-1, something that is always a good demonstration to have in hand. There are a few other beneficial mutations with a small human population to examine, such as those related to reduced blood lipids or myostatin loss of function; we may see many of these lines of research result in therapies in the years ahead.
And yet! While there will no doubt be an avalanche of funding into bringing PAI-1 inhibitors to the clinic, ask yourself this: if tinkering with a fraction of the harmful secretions of senescent cells is this beneficial, how much better will it be to remove these damaging cells entirely via senolytic therapies? All of those involved in this field should spend more time than they do on work with a higher expectation value, I believe.
[+] [-] microcolonel|8 years ago|reply
[+] [-] saalweachter|8 years ago|reply
The first is that our genetic code is spaghetti code beyond the dreams of the most cowboy of the 70's cowboy assembly programmers. Our genes and proteins are reused in different ways at different times in different cells in ways that make it difficult to unequivocally call a gene "good" or "bad".
The second is that even evaluating along the simple "does it make things survive and reproduce better?" evolutionary metric, you still need to consider the exact, current environment a gene is being evaluated in; a gene can be harmful today and beneficial yesterday, or vice versa. Maybe the gene confers an immunity to a virulent, deadly, extinct disease; maybe it was necessary when another gene was present, a gene which has since changed.
Evolution isn't particularly fast, most of the time; any given organism will be adapted to a smear of their environments as they existed over the last few million years, and not perfectly adapted to any of them (unless their environment has remained static).
[+] [-] twobyfour|8 years ago|reply
[+] [-] wyclif|8 years ago|reply
[+] [-] blacksmith_tb|8 years ago|reply
1: https://www.snpedia.com/index.php/Rs1799889
[+] [-] mamoswined|8 years ago|reply
[+] [-] unknown|8 years ago|reply
[deleted]
[+] [-] squAmishCells|8 years ago|reply
[deleted]