Telomerase Enhanced Mice Live Longer, and Longer Still When Calorie Restricted
These past few years, researchers have produced several demonstrations of extended life and reduced cancer rates in mice through the use of various gene therapy combinations involving increased telomerase expression and extra copies of cancer suppression genes such as P53. You can find an overview of this research and pointers to a review paper back in last year's archives.
A few years ago, a Spanish research team created transgenic mice that lived significantly longer than normal by combining increased p53 with increased telomerase. p53 is a cancer suppressor that under usual circumstances reduces the ability of stem cells to replace worn cells in aging tissue - less cell proliferation means a lower chance of cancer over time, but also faster aging as the tissues of the body wear and fail more readily. More telomerase, on the other hand, achieves the opposite end: dynamic, longer lasting cells that also produce way more cancers in the course of their more energetic operations. This, in any case, is the consensus view of how these elements work in the biochemistry of mammals.The researchers recently published results for the next stage of their research program: taking the modifications that had been transgenic to date and instead applying them as gene therapies to adult mice.
That was last year. The latest update to arrive this month has the researchers trying out calorie restriction (CR) on their transgenic telomerase-enhanced (TgTERT) mice, with a wild-type (WT) control group. Apparently calorie restriction somewhat synergizes with the effects of additional telomerase, and thus calorie restricted TgTERT mice live longer than their ad libitum peers. Beyond that, this is also a study of how calorie restriction impacts telomere dynamics, finding that it delays the characteristic erosion of telomeres with age - which is consistent with the body of research showing calorie restriction to slow almost all other measurable aspects of aging.
First, we showed that the CR protocol used here was able to protect from the development of pathologies associated with aging in both WT and TgTERT mice, including insulin sensitivity and glucose intolerance, as well as protection from bone loss over time. In addition to protection from age-related pathologies, CR improved other aspects of mouse health such neuromuscular coordination in both genotypes. Together, these results indicate that the CR protocol used in this study was able to increase the "health span" of both WT and TgTERT mice.In agreement with this, we observed a delayed onset of first deaths in the WT and TgTERT cohorts under CR. Interestingly, WT mice under CR showed a similar median longevity and similar onset of first deaths to that in TgTERT mice under a control diet, suggesting that TERT transgenic expression is partially the beneficial effects of CR.
By using longitudinal telomere length studies, we also describe here that CR delays telomere shortening associated to aging in blood cells from WT mice (PBLs), to an analogous degree to that observed associated to TERT over-expression. Other tissues, such as lung, kidney, bone marrow and muscle, also presented longer telomeres in mice under CR compared to those under the control diet. In agreement with a protection from telomere shortening associated with aging, we also observed that CR protected from telomere-originated DNA damage and chromosomal aberrations.
The trouble with ascribing causes and mechanisms to calorie restriction is that it does change everything. So autophagy researchers see it boosting autophagy, telomerase researchers see it changing telomere dynamics, fat metabolism researchers see it affecting fat metabolism, and so forth. So far I think that autophagy has a stronger claim than any other mechanism as being the dominant cause of calorie restriction benefits to health and longevity, if only because removal of mechanisms essential to autophagy has been shown to remove those benefits in some laboratory species. But there's still plenty of room for evidence and debate.
One important fact that seems to get lost in all this is that CR alone did not alter longevity- the CR mice did NOT live longer. We could suspect they had longer health spans but not longer life spans. There are only one or two specific breeds of mice that have shown any life extension with CR. The other things to keep in mind is that Dr Blasco's mice began their calorie restriction at age 3 months and kept it up for their entire life. This would be the equivalent of starting it when you were 18 and doing it for the rest of your life! In light of all the recent findings the sirtuin pathway and CR must be properly interpreted: they are metabolic stress pathways that may improve health span but are not longevity factors. So far the only thing that seems to extend life in mammals is over expression of telomerase. Yet you will continue to see the following statement: CR is the only robust way to extend life. Maybe if you are a fruit fly! That said it is certainly worth defining what degree of calorie restriction would be needed in specific diseases in humans to improve health span. One would think it might be different in heart disease than cancer! David Woynarowski MD author The Immortality Edge
The tolemarase spring compression repair can also be investigated based on Autophaging:
There must be definite connection between autophaging spring compression repairing by Mitochondria involvement.This indicates a betterment using rapamyc in that may supress the immune like pencillin.This can also be observed while the health line of palm print attacking the life line may be fading away in due course of time. Swiss pharmaceutical giant, has begun taking the first steps to position a version of rapamycin as the first true anti-aging drug. The drug appears to delay "age-related decline in multiple different organ systems, which is something we would expect if we were fundamentally slowing the aging process.It's too early to say what the proper dose of glycine might be, but we can speculate that it would be enough to bring glycine levels up to those seen in young people. Glycine is probably increasing levels of glutathione in mitochondria, and since glutathione is the cells' and the mitochondria's main internal antioxidant, this protects them from oxidative damage and keeps them in a youthful state.