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human longevity

Philip M C Davy, D Craig Willcox, Michio Shimabukuro, Timothy A Donlon, Trevor Torigoe, Makoto Suzuki, Moritake Higa, Hiroaki Masuzaki, Masataka Sata, Randi Chen, Rachel Murkofsky, Brian J Morris, Eunjung Lim, Richard C Allsopp, Bradley J Willcox
FOXO3 is one of the most prominent genes demonstrating a consistently reproducible genetic association with human longevity. The mechanisms by which these individual gene variants confer greater organismal lifespan are not well understood. We assessed the effect of longevity-associated FOXO3 alleles on age-related leukocyte telomere dynamics in a cross-sectional study comprising of samples from 121 healthy Okinawan-Japanese donors aged 21-95 years. We found that telomere length for carriers of the longevity associated allele of FOXO3 single nucleotide polymorphism rs2802292 displayed no significant correlation with age, an effect that was most pronounced in older (>50) participants...
April 21, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Federico Sizzano, Sebastiano Collino, Ornella Cominetti, Daniela Monti, Paolo Garagnani, Rita Ostan, Chiara Pirazzini, Maria Giulia Bacalini, Daniela Mari, Giuseppe Passarino, Claudio Franceschi, Alessio Palini
The production of reactive oxygen species (ROS) may promote immunosenescence if not counterbalanced by the antioxidant systems. Cell membranes, proteins, and nucleic acids become the target of ROS and progressively lose their structure and functions. This process could lead to an impairment of the immune response. However, little is known about the capability of the immune cells of elderly individuals to dynamically counteract the oxidative stress. Here, the response of the main lymphocyte subsets to the induced oxidative stress in semisupercentenarians (CENT), their offspring (OFF), elderly controls (CTRL), and young individuals (YO) was analyzed using flow cytometry...
2018: Mediators of Inflammation
Kaitlyn N Lewis, Nimrod D Rubinstein, Rochelle Buffenstein
Mouse-sized naked mole-rats (Heterocephalus glaber), unlike other mammals, do not conform to Gompertzian laws of age-related mortality; adults show no age-related change in mortality risk. Moreover, we observe negligible hallmarks of aging with well-maintained physiological and molecular functions, commonly altered with age in other species. We questioned whether naked mole-rats, living an order of magnitude longer than laboratory mice, exhibit different plasma metabolite profiles, which could then highlight novel mechanisms or targets involved in disease and longevity...
April 20, 2018: GeroScience
Cemalettin Bekpen, Chen Xie, Almut Nebel, Diethard Tautz
The SPATA31 ( alias FAM75A) gene family belongs to the core duplicon families that are thought to have contributed significantly to hominoid evolution. It is also among the gene families with the strongest signal of positive selection in hominoids. It has acquired new protein domains in the primate lineage and a previous study has suggested that the gene family has expanded its function into UV response and DNA repair. Here we show that over-expression of SPATA31A1 in fibroblast cells leads to premature senescence due to interference with aging-related transcription pathways...
April 19, 2018: Aging
Udeme E Ekrikpo, Andre P Kengne, Effiong E Akpan, Emmanuel E Effa, Aminu K Bello, John U Ekott, Cindy George, Babatunde L Salako, Ikechi G Okpechi
Widespread use of antiretroviral therapy (ART) in human immunodeficiency virus (HIV) patients has led to improved longevity with the attendant increase in noncommunicable disease prevalence including chronic kidney disease (CKD). This study documents the prevalence of CKD in a large HIV population in Southern Nigeria.This is a single center, 15-year analysis in ART-naïve patients. CKD was defined as the occurrence of estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m on 2 consecutive occasions 3 to 12 months apart using the chronic kidney disease epidemiology collaboration (CKD-EPI) equation...
April 2018: Medicine (Baltimore)
Jingqi Fang, Jiping Yang, Xun Wu, Gangming Zhang, Tao Li, Xi'e Wang, Hong Zhang, Chih-Chen Wang, Guang-Hui Liu, Lei Wang
Metformin, an FDA-approved antidiabetic drug, has been shown to elongate lifespan in animal models. Nevertheless, the effects of metformin on human cells remain unclear. Here, we show that low-dose metformin treatment extends the lifespan of human diploid fibroblasts and mesenchymal stem cells. We report that a low dose of metformin upregulates the endoplasmic reticulum-localized glutathione peroxidase 7 (GPx7). GP×7 expression levels are decreased in senescent human cells, and GPx7 depletion results in premature cellular senescence...
April 16, 2018: Aging Cell
Archana Vijaya Kumar, Carmen Donate, Beat A Imhof, Thomas Matthes
B lymphocytes are key players in immune cell circulation and they mainly home to and reside in lymphoid organs. While normal B cells only proliferate when stimulated by T lymphocytes, oncogenic B cells survive and expand autonomously in undefined organ niches. Mantle cell lymphoma (MCL) is one such B cell disorder, where the median survival rate of patients is 4 - 5 years. This calls for the need of effective mechanisms by which the homing and engraftment of these cells are blocked in order to increase the survival and longevity of patients...
March 30, 2018: Journal of Visualized Experiments: JoVE
Doreen J Siria, Elis P A Batista, Mercy A Opiyo, Elizangela F Melo, Robert D Sumaye, Halfan S Ngowo, Alvaro E Eiras, Fredros O Okumu
BACKGROUND: Controlled blood-feeding is essential for maintaining laboratory colonies of disease-transmitting mosquitoes and investigating pathogen transmission. We evaluated a low-cost artificial feeding (AF) method, as an alternative to direct human feeding (DHF), commonly used in mosquito laboratories. METHODS: We applied thinly-stretched pieces of polytetrafluoroethylene (PTFE) membranes cut from locally available seal tape (i.e. plumbers tape, commonly used for sealing pipe threads in gasworks or waterworks)...
April 11, 2018: Parasites & Vectors
Marie Louise Jahn, Maria Abildgaard Steffensen, Jan Pravsgaard Christensen, Allan Randrup Thomsen
Defining correlates of T cell mediated protection is important in order to accelerate the development of efficient T cell based vaccines conferring long-term immunity. Extensive studies have provided important insight regarding the characteristics and functional properties of the effector and memory CD8 T cells induced by viral vector based vaccines. However, long-term protection has been difficult to achieve with T cell inducing vaccines, and the determinants underlying this loss in protection over time are still not fully defined...
April 4, 2018: Vaccine
Shawn M Ferguson
Lysosomes support diverse cellular functions by acting as sites of macromolecule degradation and nutrient recycling. The degradative abilities of lysosomes are conferred by a lumen that is characterized by an acidic pH and which contains numerous hydrolases that support the breakdown of major cellular macromolecules to yield cellular building blocks (amino acids, nucleic acids, sugars, lipids and metals) that are transported into the cytoplasm for their re-use. In addition to these important hydrolytic and recycling functions, lysosomes also serve as a signaling platform that integrates nutrient and metabolic cues to control signaling via the mTORC1 pathway...
April 4, 2018: Neuroscience Letters
Alexander M Vaiserman
Increasing evidence suggests that risk for age-related disease and longevity can be programmed early in life. In human populations, convincing evidence has been accumulated indicating that intrauterine growth restriction (IUGR) resulting in low birth weight (<2.5 kg) followed by postnatal catch-up growth is associated with various aspects of metabolic syndrome, type 2 diabetes and cardiovascular disease in adulthood. Fetal macrosomia (birth weight >4.5 kg), by contrast, is associated with high risk of non-diabetic obesity and cancers in later life...
April 4, 2018: Mechanisms of Ageing and Development
George B Stefano, Rachel Fine, Richard M Kream
Ten thousand years ago, the foundation for agricultural development and animal domestication was laid. Neolithic founder crops were carbohydrate-laden cereal grasses that facilitated transformation of hunter-gather societies into ancient civilizations with realistic capabilities for population expansion. In the last 3-4 decades, however, debilitating medical consequences of a progressively narrowed high caloric diet incorporating processed carbohydrates, animal protein, saturated fat and cholesterol, are translated into a global epidemic of obesity linked to metabolic and endocrine disorders, which, in part, emerged from the enhancement of our longevity...
April 7, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Andrei Seluanov, Vadim N Gladyshev, Jan Vijg, Vera Gorbunova
Cancer researchers have traditionally used the mouse and the rat as staple model organisms. These animals are very short-lived, reproduce rapidly and are highly prone to cancer. They have been very useful for modelling some human cancer types and testing experimental treatments; however, these cancer-prone species offer little for understanding the mechanisms of cancer resistance. Recent technological advances have expanded bestiary research to non-standard model organisms that possess unique traits of very high value to humans, such as cancer resistance and longevity...
April 5, 2018: Nature Reviews. Cancer
Jeong-Hwan Park, Jeong-Woo Park, Ju-Hyeon Lee, Dong-Yun Kim, Jeong-Hoon Hahm, Young-Seuk Bae
We have previously shown that phospholipase D (PLD) downregulation accelerates cellular senescence, which is widely believed to play an important role in aging, by stimulating reactive oxygen species (ROS) accumulation in human cells. In this study, we examined the role of PLD in aging using the nematode Caenorhabditis elegans. The mRNA level of pld-1 was found to be inversely correlated with aging. RNAi-mediated knockdown of pld-1 expression in nematodes enhanced ROS and lipofuscin accumulation and decreased lifespan, motility, and resistance to stress compared to that in nematodes treated with control RNAi...
April 6, 2018: Experimental & Molecular Medicine
Jin Young Lee, Changhwan Kim, Yong Han Lee
A sensitive method for the purification and determination of two protein adducts, organophosphorus (OP)-BChE and OP-albumin adducts, in a single sample using a simultaneous sample preparation method was developed and validated using liquid chromatography-tandem mass spectrometry. First, we isolated O-ethyl S-2-diisopropylaminoethyl methyl phosphonothiolate (VX) and O-pinacolyl methylphosphonofluoridate (soman, GD)-BChE adducts using an immunomagnetic separation (IMS) method and the HiTrap™ Blue affinity column was subsequently used to isolate and purify VX and GD-albumin adducts from the plasma of rhesus monkeys exposed to nerve agents...
March 31, 2018: Journal of Analytical Toxicology
Fan Yang, Liang Sun, Xiaoquan Zhu, Jing Han, Yi Zeng, Chao Nie, Huiping Yuan, Xiaoling Li, Xiaohong Shi, Yige Yang, Caiyou Hu, Zeping Lv, Zezhi Huang, Chenguang Zheng, Siying Liang, Jin Huang, Gang Wan, Keyan Qi, Bin Qin, Suyan Cao, Xin Zhao, Yongqiang Zhang, Ze Yang
No abstract text is available yet for this article.
March 15, 2018: Aging
Allan Sauvat, Guo Chen, Kevin Müller, Mingming Tong, Fanny Aprahamian, Sylvère Durand, Giulia Cerrato, Lucillia Bezu, Marion Leduc, Joakim Franz, Patrick Rockenfeller, Junichi Sadoshima, Frank Madeo, Oliver Kepp, Guido Kroemer
Depending on the length of their carbon backbone and their saturation status, natural fatty acids have rather distinct biological effects. Thus, longevity of model organisms is increased by extra supply of the most abundant natural cis-unsaturated fatty acid, oleic acid, but not by that of the most abundant saturated fatty acid, palmitic acid. Here, we systematically compared the capacity of different saturated, cis-unsaturated and alien (industrial or ruminant) trans-unsaturated fatty acids to provoke cellular stress in vitro, on cultured human cells expressing a battery of distinct biosensors that detect signs of autophagy, Golgi stress and the unfolded protein response...
March 27, 2018: EBioMedicine
Maria Skrzypkowska, Bartosz Słomiński, Monika Ryba-Stanisławowska, Piotr Gutknecht, Janusz Siebert
BACKGROUND: KLOTHO is a regulator of endothelial cells activity and integrity. It has been described for the first time because of its anti-aging properties. KLOTHO encoding gene is present in many functional variants in humans, including "KL-VS" variant that has been connected with longevity and cardiovascular disease development. Few mechanisms have been proposed to explain these associations, but none of them focused on cells from CD34+ population. The aim of our study was to investigate influence of KLOTHO KL-VS polymorphism on populations of CD34+ and CD34+VEGFR2+ cells...
March 28, 2018: Microvascular Research
Niels van den Berg, Mar Rodriguez-Girondo, Anton J M de Craen, Jeanine J Houwing-Duistermaat, Marian Beekman, P Eline Slagboom
Members of longevous families live longer than individuals from similar birth cohorts and delay/escape age related diseases. Insight into this familial component of longevity can provide important knowledge about mechanisms protecting against age-related diseases. This familial component of longevity was studied in the Leiden Longevity Study which consists of 944 longevous siblings (participants), their parents (N=842), siblings (N=2302), and spouses (N=809). Family longevity scores were estimated to explore whether human longevity is transmitted preferentially through the maternal or paternal line...
March 27, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Daniel T Utzschneider, Arnaud Delpoux, Dominik Wieland, Xin Huang, Chen-Yen Lai, Maike Hofmann, Robert Thimme, Stephen M Hedrick
Immunity following an acutely resolved infection or the long-term equipoise of chronic viral infections often depends on the maintenance of antigen-specific CD8+ T cells, yet the ongoing transcriptional requirements of these cells remain unclear. We show that active and continuous programming by FOXO1 is required for the functional maintenance of a memory population. Upon Foxo1 deletion following resolution of an infection, memory cells rapidly lost their characteristic gene expression, gradually declined in number, and were impaired in self-renewal...
March 27, 2018: Cell Reports
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