Fatty Acids Correlate with Longevity in Bird Species
Birds, like bats, have high metabolic rates due to the demands of flight but are also long-lived in comparison to similarly sized members of other species. This has a lot to do with mitochondria and membrane fatty acid composition, as shown by the evidence in the paper linked below. The membrane pacemaker theory of aging tells us that the genetically determined ratios of specific fatty acids in cell membranes determine resistance to oxidative damage, as well as other important properties in the operation of metabolism that are particularly relevant to mitochondrial function and the ways in which mitochondria become damaged in aging. From a practical point of view, this is one of the things that should steer our attention towards mitochondrial DNA damage as an important contribution to aging, and cause us to prioritize research on methods of repair of that damage.
The evolution of lifespan is a central question in evolutionary biology, begging the question why there is so large variation among taxa. Specifically, a central quest is to unravel proximate causes of ageing. Here we show that the degree of unsaturation of liver fatty acids predicts maximum lifespan in 107 bird species. In these birds, the degree of fatty acid unsaturation is positively related to maximum lifespan across species. This is due to a positive effect of monounsaturated fatty acid content, while polyunsaturated fatty acid content negatively correlates with maximum lifespan. Furthermore, fatty acid chain length unsuspectedly increases with maximum lifespan independently of degree of unsaturation. These findings tune theories on the proximate causes of ageing while providing evidence that the evolution of lifespan in birds occurs in association with fatty acid profiles. This finding suggests that studies of proximate and ultimate questions may facilitate our understanding of these central evolutionary questions.
Significant mitochondrial dysfunction comes from the telomeres - P53 - Mito aging axim:
http://www.nature.com/nrm/journal/v13/n6/fig_tab/nrm3352_F2.html
"Telomerase reactivation or PGC overexpression can reverse PGC-associated metabolic and mitochondrial changes in mice with established telomere dysfunction. Telomere dysfunction may also lead to compromised mitochondrial function and energy metabolism through other pathways (dashed arrows)."
This same mechanic exists in humans too. PGC-1a increase has also been demonstrated to regulate TERT expression and thus restore telomeres as a feedback.
From the paper:
http://www.nature.com/nrm/journal/v13/n6/full/nrm3352.html
In short mitochondrial function and short telomeres have increasingly been implicated as being closely linked with the former cascading into the latter. Decline of telomerase activity is also linked to Mito dysfunction. There is a reason why a number of researchers think restoration of telomerase/telomeres will also address significant mitochondria function.
Another Dephino paper again showing the increasingly obvious link between Mitochondria and Telomeres.This time in the heart but again showing the link between the two and that there are potential approaches to tackle both issues.
http://circres.ahajournals.org/content/110/9/1226.full
http://circres.ahajournals.org/content/110/9/1226.full
And even more evidence showing the link between the two. Fix one it will help the other.
http://www.researchgate.net/publication/49823573_Telomere_dysfunction_induces_metabolic_and_mitochondrial_compromise._Nature
Steve, as always you lay out a compelling case for telomere restoration having a potential positive effect. Know where a poor schmuck like me could get his mitts on something to replenish them?
Seth that is the problem, there is very little one can do to replenish them. However there is plenty you can do to erode them faster. Smoking, sedentary lifestyle, lack of exercise all contribute.
TA-65 is a very weak inducer of telomerase but probably ~5% of the required strength. Still some of the papers studying its use have shown benefits to using it, mostly in the immune system. Personally I think it is overpriced. Some people use astragalus root to induce telomerase, the data is shaky for that though.
The "telomere-p53-PGC axis" as proposed by DePhino links telomeres and Mitochondrial function very convincingly. Certainly the telomere-p53-PGC axis is not the only contributor to Mitochondrial dysfunction and decline but the mechanism proposed certainly explains the link between the two and how it contributes to stem cell decline and Mitochondrial decline as well as metabolic decline and ultimately aging and organ/tissue failure.
I am currently investigating the validity of PCG-1a to regulate TERT because if it does it demonstrates a feedback loop that creates a downward spiral of telomere loss and mitochondrial decline, increasingly P53 and increasing oxidative stress. More on that later if I can confirm the data from the Alexander linked study here.
How do telomeres affect the genetically determined ratios of specific fatty acids in cell membranes and mitochondrial membranes Steve? Or are you suggesting that the strong correlation between this variable and lifespan is spurious??
Interesting question jim. That's something to investigate further I think.it could be influenced by the pcg pathway linking telomeres, mitochondria and metabolism. I will see what I can find out. Not that everything relates to telomeres of course.
Steve: I think the reason people are asking is that the post is about this fatty acid correlation, and in that context your material on telomerase seems mostly to be a non sequitur.
Steve, is your enthusiasm for telomerase not at all tempered by the extensive evidence that elevating telomerase activity creates a permissive environment for cancer?
:
http://www.nature.com/onc/journal/v24/n13/full/1208413a.html
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC139804/
http://emboj.embopress.org/content/20/11/2619.long
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053760em
(Same transgene as above but on a different background strain).
http://www.pnas.org/content/99/12/8191.full
http://mcb.asm.org/content/24/10/4275.full
http://dx.doi.org/10.1016/j.cell.2012.01.039
http://jnci.oxfordjournals.org/content/107/6/djv074
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3611810/
Tempered yes but I have seen plenty of research that suggests optimal telomeres offer a level of cancer protection and other benefits. The idea that induction of telomerase will translate to cancer is an old idea and even some of the people who initially suggested it have changed their stance.obviously there are two camps on telomerase and we both know the papers for and against it. Ironically the first paper you cited is by Maria blasco a person who urged caution initially but is now activity working on telomerase therapy as well as cancer therapies. Not to say caution is to be thrown to the wind but no I remain unconvinced the risk outweigh the potential benefits.
Also note we are not talking about permanently upregulation of TERT here we are talking about transient delivery of said gene in order to reset telomeres. Similar to what Helen Blau did this year where the therapy was transient to 48 hours, enough time to refresh telomeres but not immortalizing the cells, this was confirmed by the Blau lab that not imortalization occured which ofc is not wanted.
The Danish study was flawed for reasons which Josh Mitteldorf explains here:
http://joshmitteldorf.scienceblog.com/2015/04/29/large-new-survey-tracks-telomere-length-and-mortality/
Further discussion on the cancer theory and why people like Blasco also have changed their stance on it
http://joshmitteldorf.scienceblog.com/2015/04/22/telomerase-does-not-cause-cancer/