Longevity and Life Span

We all try to improve our life span. But our life span is already 122 years, proven by example…

We know a human can become 122 years, proven by Jeanne Calment. More people already reached 115 years, and 100 is not very unique anymore. The first target should be reaching 120 years in a very good condition, physically and mentally. Only then, it makes sence to find out about becoming even older. Basically, it should be possible, according to Aubrey the Grey, to become 150 years and even older. His focus is on engineered negligible senescence, a tissue repair strategy intended to rejuvenate the human body and thereby allow an indefinite lifespan. His focus is on seven different targets causing tissue damage and so aging. The idea is to avoid the damage in the first place, however this makes lifes difficult. So some strategies need to be developed to reverse this damage. Since the body has the ability to self recover, we should choose the life style and foods or supplements who promotes this self recovery process. Only after managing this process it becomes interested to think about life extension.

Studies on longevity;

Inhibition of specific HDACs and sirtuins suppresses pathogenesis in a Drosophila model of Huntington's disease.

Pallos J, Bodai L, Lukacsovich T, Purcell JM, Steffan JS, Thompson LM, Marsh JL.
Department of Developmental and Cell Biology, University of California, Irvine, CA 92697 USA. Hum Mol Genet. 2008 Sep 1.

Huntington's disease (HD) is associated with transcriptional dysregulation and multiple studies with histone deacetylase (HDAC) inhibitors suggest that global approaches to restoring transcriptional balance and appropriate protein acetylation are therapeutically promising. To determine whether more targeted approaches might be effective, we have tested the impact of all the HDACs in Drosophila on Htt induced pathology. Among the zinc-dependent or "classical" HDACs, we find that neurodegeneration is most sensitive to levels of Rpd3. We also find that among the NAD(+)-dependent class III deacetylases, genetic or pharmacologic reduction of either Sir2 or Sirt2 provides neuroprotection to Htt challenged animals and that even greater neuroprotection is achieved when Rpd3 and Sir2 are simultaneously reduced. Our experiments suggest that longevity promoting strategies may be distinct from those that protect against neurodegeneration in Drosophila challenged with mutant human Htt. These results highlight a novel therapeutic approach for HD in the form of Sir2 inhibition and possible combinatorial inhibition of Sir2 and Rpd3.

Vascular superoxide and hydrogen peroxide production and oxidative stress resistance in two closely related rodent species with disparate longevity.

Aging Cell. 2007 Dec;6(6):783-97. Epub 2007 Oct 8.

Csiszar A, Labinskyy N, Zhao X, Hu F, Serpillon S, Huang Z, Ballabh P, Levy RJ, Hintze TH, Wolin MS, Austad SN, Podlutsky A, Ungvari Z.
Department of Physiology, New York Medical College, Valhalla, NY 10595, USA. anna_csiszar@nymc.edu

Vascular aging is characterized by increased oxidative stress, impaired nitric oxide (NO) bioavailability and enhanced apoptotic cell death. The oxidative stress hypothesis of aging predicts that vascular cells of long-lived species exhibit lower production of reactive oxygen species (ROS) and/or superior resistance to oxidative stress. We tested this hypothesis using two taxonomically related rodents, the white-footed mouse (Peromyscus leucopus) and the house mouse (Mus musculus), that show a more than twofold difference in maximum lifespan potential (MLSP = 8 and 3.5 years, respectively). We compared interspecies differences in endothelial superoxide (O2-) and hydrogen peroxide (H2O2) production, NAD(P)H oxidase activity, mitochondrial ROS generation, expression of pro- and antioxidant enzymes, NO production, and resistance to oxidative stress-induced apoptosis. In aortas of P. leucopus, NAD(P)H oxidase expression and activity, endothelial and H2O2 production, and ROS generation by mitochondria were less than in mouse vessels. In P. leucopus, there was a more abundant expression of catalase, glutathione peroxidase 1 and hemeoxygenase-1, whereas expression of Cu/Zn-SOD and Mn-SOD was similar in both species. NO production and endothelial nitric oxide synthase expression was greater in P. leucopus. In mouse aortas, treatment with oxidized low-density lipoprotein (oxLDL) elicited substantial oxidative stress, endothelial dysfunction and endothelial apoptosis (assessed by TUNEL assay, DNA fragmentation and caspase 3 activity assays). According to our prediction, vessels of P. leucopus were more resistant to the proapoptotic effects of oxidative stressors (oxLDL and H2O2). Primary fibroblasts from P. leucopus also exhibited less H2O2-induced DNA damage (comet assay) than mouse cells. Thus, increased lifespan potential in P. leucopus is associated with a decreased cellular ROS generation and increased oxidative stress resistance, which accords with the prediction of the oxidative stress hypothesis of aging.

Exp Gerontol. 2006 Apr;41(4):417-29. Epub 2006 Mar 9.


Caloric restriction and growth hormone receptor knockout: effects on expression of genes involved in insulin action in the heart.

Masternak MM, Al-Regaiey KA, Del Rosario Lim MM, Jimenez-Ortega V, Panici JA, Bonkowski MS, Kopchick JJ, Wang Z, Bartke A.
Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794, USA. mmasternak@siumed.edu

Blockade of growth hormone (GH), decreased insulin-like growth factor-1 (IGF1) action and increased insulin sensitivity are associated with life extension and an apparent slowing of the aging process. We examined expression of genes involved in insulin action, IR, IRS1, IRS2, IGF1, IGF1R, GLUT4, PPARs and RXRs in the hearts of normal and GHR-/- (KO) mice fed ad libitum or subjected to 30% caloric restriction (CR). CR increased the cardiac expression of IR, IRS1, IGF1, IGF1R and GLUT4 in normal mice and IRS1, GLUT4, PPARalpha and PPARbeta/delta in GHR-KO animals. Expression of IR, IRS1, IRS2, IGF1, GLUT4, PPARgamma and PPARalpha did not differ between GHR-KO and normal mice. These unexpected results suggest that CR may lead to major modifications of insulin action in the heart, but high insulin sensitivity of GHR-KO mice is not associated with alterations in the levels of most of the examined molecules related to intracellular insulin signaling.