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Yasumichi Arai, Takashi Sasaki, Nobuyoshi Hirose
The scope and purpose of this review was to summarize the aims, methods, findings, and future of centenarian and (semi)-supercentenarian studies in Japan, particularly those from our own interdisciplinary laboratory. Medically, approximately 97% of centenarians contract chronic diseases including hypertension and gastrointestinal disease; however, they present with few cardiovascular risk factors. The low prevalence of diabetes mellitus and carotid atherosclerotic plaques is peculiarities of centenarians, which could be associated with high adiponectin levels...
February 16, 2017: Mechanisms of Ageing and Development
Robert D Young
No abstract text is available yet for this article.
February 2017: Rejuvenation Research
Daniela Monti, Rita Ostan, Vincenzo Borelli, Gastone Castellani, Claudio Franceschi
Inflammaging is a recent theory of aging originally proposed in 2000 where data and conceptualizations regarding the aging of the immune system (immunosenescence) and the evolution of immune responses from invertebrates to mammals converged. This theory has received an increasing number of citations and experimental confirmations. Here we present an updated version of inflammaging focused on omics data - particularly on glycomics - collected on centenarians, semi-supercentenarians and their offspring. Accordingly, we arrived to the following conclusions: i) inflammaging has a structure where specific combinations of pro- and anti-inflammatory mediators are involved; ii) inflammaging is systemic and more complex than we previously thought, as many organs, tissues and cell types participate in producing pro- and anti-inflammatory stimuli defined "molecular garbage"; iii) inflammaging is dynamic, can be propagated locally to neighboring cells and systemically from organ to organ by circulating products and microvesicles, and amplified by chronic age-related diseases constituting a "local fire", which in turn produces additional inflammatory stimuli and molecular garbage; iv) an integrated Systems Medicine approach is urgently needed to let emerge a robust and highly informative set/combination of omics markers able to better grasp the complex molecular core of inflammaging in elderly and centenarians...
December 27, 2016: Mechanisms of Ageing and Development
Noriyuki Fuku, Rafael Alis, Thomas Yvert, Hirofumi Zempo, Hisashi Naito, Yukiko Abe, Yasumichi Arai, Haruka Murakami, Motohiko Miyachi, Helios Pareja-Galeano, Enzo Emanuele, Nobuyoshi Hirose, Alejandro Lucia
Myostatin (MSTN) and α-actinin-3 (ACTN3) genes are potentially associated with preservation of muscle mass and oxidative capacity, respectively. To explore the possible role of these genes in exceptional longevity (EL), the allele/genotype frequency distribution of two polymorphisms in MSTN (rs1805086, K153R) and ACTN3 (rs1815739, R577X) was studied in Japanese centenarians of both sexes (n = 742) and healthy controls (n = 814). The rs1805086 R-allele (theoretically associated with muscle mass preservation at the expense of oxidative capacity) was virtually absent in the two groups, where genotype distributions were virtually identical...
2016: PloS One
Masaki Takao, Nobuyoshi Hirose, Yasumichi Arai, Ban Mihara, Masaru Mimura
Supercentenarians (aged 110 years old or more) are extremely rare in the world population (the number of living supercentenarians is estimated as 47 in the world), and details about their neuropathological information are limited. Based on previous studies, centenarians (aged 100-109 years old) exhibit several types of neuropathological changes, such as Alzheimer's disease and Lewy body disease pathology, primary age-related tauopathy, TDP-43 pathology, and hippocampal sclerosis. In the present study, we provide results from neuropathological analyses of four supercentenarian autopsy cases using conventional and immunohistochemical analysis for neurodegenerative disorders...
2016: Acta Neuropathologica Communications
Alejandro Santos-Lozano, Ana Santamarina, Helios Pareja-Galeano, Fabian Sanchis-Gomar, Carmen Fiuza-Luces, Carlos Cristi-Montero, Aranzazu Bernal-Pino, Alejandro Lucia, Nuria Garatachea
As the world population ages, so the prevalence increases of individuals aged 100 years or more, known as centenarians. Reaching this age has been described as exceptional longevity (EL) and is attributed to both genetic and environmental factors. Many genetic variations known to affect life expectancy exist in centenarians. This review of studies conducted on centenarians and supercentenarians (older than 110 years) updates knowledge of the impacts on longevity of the twenty most widely investigated single nucleotide polymorphisms (SNPs)...
August 2016: Maturitas
Elena Biagi, Claudio Franceschi, Simone Rampelli, Marco Severgnini, Rita Ostan, Silvia Turroni, Clarissa Consolandi, Sara Quercia, Maria Scurti, Daniela Monti, Miriam Capri, Patrizia Brigidi, Marco Candela
The study of the extreme limits of human lifespan may allow a better understanding of how human beings can escape, delay, or survive the most frequent age-related causes of morbidity, a peculiarity shown by long-living individuals. Longevity is a complex trait in which genetics, environment, and stochasticity concur to determine the chance to reach 100 or more years of age [1]. Because of its impact on human metabolism and immunology, the gut microbiome has been proposed as a possible determinant of healthy aging [2, 3]...
June 6, 2016: Current Biology: CB
Steve Horvath, Chiara Pirazzini, Maria Giulia Bacalini, Davide Gentilini, Anna Maria Di Blasio, Massimo Delledonne, Daniela Mari, Beatrice Arosio, Daniela Monti, Giuseppe Passarino, Francesco De Rango, Patrizia D'Aquila, Cristina Giuliani, Elena Marasco, Sebastiano Collino, Patrick Descombes, Paolo Garagnani, Claudio Franceschi
Given the dramatic increase in ageing populations, it is of great importance to understand the genetic and molecular determinants of healthy ageing and longevity. Semi-supercentenarians (subjects who reached an age of 105-109 years) arguably represent the gold standard of successful human ageing because they managed to avoid or postpone the onset of major age-related diseases. Relatively few studies have looked at epigenetic determinants of extreme longevity in humans. Here we test whether families with extreme longevity are epigenetically distinct from controls according to an epigenetic biomarker of ageing which is known as "epigenetic clock"...
December 2015: Aging
Yasumichi Arai, Carmen M Martin-Ruiz, Michiyo Takayama, Yukiko Abe, Toru Takebayashi, Shigeo Koyasu, Makoto Suematsu, Nobuyoshi Hirose, Thomas von Zglinicki
To determine the most important drivers of successful ageing at extreme old age, we combined community-based prospective cohorts: Tokyo Oldest Old Survey on Total Health (TOOTH), Tokyo Centenarians Study (TCS) and Japanese Semi-Supercentenarians Study (JSS) comprising 1554 individuals including 684 centenarians and (semi-)supercentenarians, 167 pairs of centenarian offspring and spouses, and 536 community-living very old (85 to 99 years). We combined z scores from multiple biomarkers to describe haematopoiesis, inflammation, lipid and glucose metabolism, liver function, renal function, and cellular senescence domains...
October 2015: EBioMedicine
Tara Akhtarkhavari, Mohammad Taghi Joghataei, Zohreh Fattahi, Mohammad Reza Akbari, Farzaneh Larti, Hossein Najmabadi, Kimia Kahrizi
BACKGROUND: The genetic basis of longevity is an important field of study because the majority of supercentenarian cases experience healthy aging and may only show age-related diseases in their last few years of life. It is clear that genetic factors play an important role in survival beyond 90 years of age, but the exact relationship of genetic variants to this phenomenon remains unknown. OBJECTIVE: The aim of this project was to investigate different hypotheses that describe the relationship between genetic variants and human longevity in a living Iranian man by Whole Exome Sequencing...
October 2015: Archives of Iranian Medicine
Fadime Tosun, Metehan Ozen, Cihad Tatar, Huseyin Alakus
Improvement of living and socioeconomic conditions, developments, and innovations in medicine and technology has prolonged of life expectancy. We provided spinal anesthesia for a 111-year-old woman requiring internal fixation of a fractured femur. The operation lasted 75 minutes. After surgery, the patient was monitored in the intensive care unit overnight. The patient was discharged from the intensive care unit after 24-hour monitoring without any complications. She was discharged from the hospital on postoperative day 2...
October 1, 2015: A & A Case Reports
Steve Horvath, Vei Mah, Ake T Lu, Jennifer S Woo, Oi-Wa Choi, Anna J Jasinska, José A Riancho, Spencer Tung, Natalie S Coles, Jonathan Braun, Harry V Vinters, L Stephen Coles
Studies that elucidate why some human tissues age faster than others may shed light on how we age, and ultimately suggest what interventions may be possible. Here we utilize a recent biomarker of aging (referred to as epigenetic clock) to assess the epigenetic ages of up to 30 anatomic sites from supercentenarians (subjects who reached an age of 110 or older) and younger subjects. Using three novel and three published human DNA methylation data sets, we demonstrate that the cerebellum ages more slowly than other parts of the human body...
May 2015: Aging
Robert D Young, Mark E Muir, John M Adams
No abstract text is available yet for this article.
February 2015: Rejuvenation Research
Dorothee Nickles, Lohith Madireddy, Nihar Patel, Noriko Isobe, Bruce L Miller, Sergio E Baranzini, Joel H Kramer, Jorge R Oksenberg
Although numerous genetic variants affecting aging and mortality have been identified, for example, apolipoprotein E ε4, the genetic component influencing cognitive aging has not been fully defined yet. A better knowledge of the genetics of aging will prove helpful in understanding the underlying biological processes. Here, we describe the whole genome sequences of 2 female octogenarians. We provide the repertoire of genomic variants that the 2 octogenarians have in common. We also describe the overlap with the previously reported genomes of 2 supercentenarians—individuals aged ≥110 years...
March 2015: Neurobiology of Aging
L Robert, J Labat-Robert
Longevity is different for every animal species as well as their genome, suggesting a correlation between genes and life-span. Estimates put the genetic effect from 5 to 35% approximately, suggesting that even genetic effects are dependent on environmental conditions. This contention is largely confirmed by the study of identical twins raised apart. They do not die at the same age and also for different reasons. Aging is not "genetically programmed", it is outside evolutionary constraint. Evolution favors early and efficient reproduction, but does not care for longevity...
February 2015: Biogerontology
Hinco J Gierman, Kristen Fortney, Jared C Roach, Natalie S Coles, Hong Li, Gustavo Glusman, Glenn J Markov, Justin D Smith, Leroy Hood, L Stephen Coles, Stuart K Kim
Supercentenarians (110 years or older) are the world's oldest people. Seventy four are alive worldwide, with twenty two in the United States. We performed whole-genome sequencing on 17 supercentenarians to explore the genetic basis underlying extreme human longevity. We found no significant evidence of enrichment for a single rare protein-altering variant or for a gene harboring different rare protein altering variants in supercentenarian compared to control genomes. We followed up on the gene most enriched for rare protein-altering variants in our cohort of supercentenarians, TSHZ3, by sequencing it in a second cohort of 99 long-lived individuals but did not find a significant enrichment...
2014: PloS One
Alejandro Santos-Lozano, Fabian Sanchis-Gomar, Helios Pareja-Galeano, Carmen Fiuza-Luces, Enzo Emanuele, Alejandro Lucia, Nuria Garatachea
The world population is continuously aging, and centenarians may be considered to be the most successfully aged individuals. Among people who reach extreme longevity (EL; i.e., >95 years), supercentenarians (SCs; aged ≥110 years) represent a subgroup of great scientific interest. Unfortunately, data on the worldwide distribution of SCs remain scarce. Therefore, this study was designed to investigate this issue. Current available data indicate that Japan is the country with the highest number of currently alive SCs...
February 2015: Rejuvenation Research
Juliana da Silva Antero-Jacquemin, Geoffroy Berthelot, Adrien Marck, Philippe Noirez, Aurélien Latouche, Jean-François Toussaint
Life-span trends progression has worldwide practical implications as it may affect the sustainability of modern societies. We aimed to describe the secular life-span trends of populations with a propensity to live longer-Olympians and supercentenarians-under two hypotheses: an ongoing life-span extension versus a biologic "probabilistic barrier" limiting further progression. In a study of life-span densities (total number of life durations per birth date), we analyzed 19,012 Olympians and 1,205 supercentenarians deceased between 1900 and 2013...
August 2015: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
L Robert, T Fulop
Regulation of longevity depends on genetic and environmental factors. According to Svanborg, a Swedish geriatrician, over the last decades human life expectancy increased as well as the age at onset of fatal diseases. Nevertheless, autopsies of centenarians revealed the presence of several severe pathologies which could have killed them much earlier. Therefore, the emphasis is on regulation of resistance dependent on the expression of genes such as Sirtuins, mTOR pathway and others controlling body resistance...
2014: Interdisciplinary Topics in Gerontology
Nuria Garatachea, Enzo Emanuele, Miguel Calero, Noriyuki Fuku, Yasumichi Arai, Yukiko Abe, Haruka Murakami, Motohiko Miyachi, Thomas Yvert, Zoraida Verde, Ma Ascensión Zea, Letizia Venturini, Catalina Santiago, Alejandro Santos-Lozano, Gabriel Rodríguez-Romo, Giovanni Ricevuti, Nobuyoshi Hirose, Alberto Rábano, Alejandro Lucia
The ApoE gene is associated with the risk of Alzheimer or cardiovascular disease but its influence on exceptional longevity (EL) is uncertain. Our primary purpose was to determine, using a case-control design, if the ApoE gene is associated with EL. We compared ApoE allele/genotype frequencies among the following cohorts: cases (centenarians, most with 1+ major disease condition; n=163, 100-111years) and healthy controls (n=1039, 20-85years) from Spain; disease-free cases (centenarians; n=79, 100-104years) and healthy controls (n=597, age 27-81years) from Italy; and cases (centenarians and semi-supercentenarians, most with 1+ major disease condition; n=729, 100-116years) and healthy controls (n=498, 23-59years) from Japan...
May 2014: Experimental Gerontology
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