Michael R Posted December 26, 2014 Report Share Posted December 26, 2014 All:Rapamycin is by far the best-supported drug (or "drug-type" supplement) potential anti-aging therapy, as most or all of you should know; it is thought to work by inhibiting mTOR, thereby inhibiting protein synthesis and boosting autophagy. Its interactions with the mechanisms of CR in mammals are complex but seemingly not very overlapping, as discussed eg here , here, and most cogently in this context here, suggesting the tantalizing possibility that rapamycin might not be a "CR mimetic" as once thought, but engage a different anti-aging pathway that might be additive to or synergistic with CR mimetics or CR itself. The biggest heretofore-identified potential roadblocks to the use of rapamycin or some modified mTOR inhibitor as anti-aging interventions in humans are diabetic-like side-effects and immune suppression seen in patients given rapamycin for existing indications (mostly, exactly to suppress the immune system, as especially after transplantation). Now, a new study reports that rapamycin can actually enhance the immunological response to vaccination in aging humans: ... we evaluated whether the mTOR inhibitor RAD001 [Everolimus -- a rapamycin analog ("rapalog")] ameliorated immunosenescence (the decline in immune function during aging) in elderly volunteers, as assessed by their response to influenza vaccination. RAD001 enhanced the response to the influenza vaccine by about 20% at doses that were relatively well tolerated. RAD001 also reduced the percentage of CD4 and CD8 T lymphocytes expressing the programmed death-1 (PD-1) receptor, which inhibits T cell signaling and is more highly expressed with age. These results raise the possibility that mTOR inhibition may have beneficial effects on immunosenescence in the elderly.(1) The most immediate caveat: simply showing the mounting of a better antibody response after short-term use of the drug is not the same thing as actually showing more effective defense against and clearance of the target pathogen after long-term use of the drug to slow the aging process. In (2), We tested how rapa and CR each impacted the immune system in adult and old mice. We report that each intervention differentially altered T-cell development in the thymus, peripheral T-cell maintenance, T-cell function and host survival after West Nile virus infection, inducing distinct but deleterious consequences to the aging immune system. The latter study has been discussed in this thread on the CR Society Listserv; I should have, but haven't yet, responded to some of Tom's objections to the latter. References1. Joan B. Mannick, Giuseppe Del Giudice, Maria Lattanzi, Nicholas M. Valiante, Jens Praestgaard, Baisong Huang, Michael A. Lonetto, Holden T. Maecker, John Kovarik, Simon Carson, David J. Glass, and Lloyd B. KlicksteinmTOR inhibition improves immune function in the elderly Sci Transl Med 24 December 2014:Vol. 6, Issue 268, p. 268ra179Sci. Transl. Med. DOI: 10.1126/scitranslmed.3009892[No PMID yet] 2. Lifespan-extending caloric restriction or mTOR inhibition impair adaptive immunity of old mice by distinct mechanisms.Goldberg EL, Romero-Aleshire MJ, Renkema KR, Ventevogel MS, Chew WM, UhrlaubJL, Smithey MJ, Limesand KH, Sempowski GD, Brooks HL, Nikolich-Žugich J.Aging Cell. 2014 Nov 26. doi: 10.1111/acel.12280. [Epub ahead of print]PMID:25424641[PubMed - as supplied by publisher] Free Article Link to comment Share on other sites More sharing options...
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