Abstract Archive

This searchable list includes the abstracts of all presentations given at a conference organised as part of the SENS series. We regret that the videos recorded at SENS3 and SENS4 are currently unavailable.

Clearance of Pathological Tau Protein with Immunotherapy

Authors: E. M. Sigurdsson
Video: (Video)

One of the perils of aging is the accumulation of various protein/peptide aggregates throughout the body, some of which are associated with toxicity. In several age-related disorders, aggregates of certain amino acid sequences are much more prominent than under normal conditions, and define the disease. Harnessing the immune system has emerged in recent years as a promising approach to treat these conditions. My laboratory has worked in this field targeting the amyloid-β peptide, the prion protein, the tau protein, and more recently the islet amyloid polypeptide.

Keywords: Tau, Tangles, Immunotherapy, Behavior, Amyloid

Tissue engineering of the liver using decellularised scaffolds

Authors: P.M. Baptista, M.M. Siddiqui, G. Lozier, S.R. Rodriguez, A. Atala, S. Soker
Video: (Video)

A major roadblock to successful organ bioengineering is the need for a functional vascular network within the engineered tissue. Here, we describe the fabrication of three-dimensional, naturally derived scaffolds with an intact vascular tree. Livers from various species were perfused with detergent to selectively remove the cellular components of the tissue while preserving the extracellular matrix components and the intact vascular network.

Keywords: endothelial, hepatocytes, billiary, transplantation, stem cells

Effect of DHEA supplementation on cognitive function in aged premenopausal rhesus macaques

Authors: K.G. Sorwell, L. Renner, A. Weiss, J. Garten, S.G. Kohama, M. Neuringer, H.F. Urbanski

The adrenal steroid dehydroepiandrosterone (DHEA) is a reliable biomarker of aging in both humans and nonhuman primates. Because the brain expresses the enzymes necessary to convert DHEA to neuroactive steroids such as estradiol (E2), the age-related decline in circulating DHEA may predispose the brain to degeneration and cognitive decline. To test this hypothesis, we administered DHEA to perimenopausal rhesus macaques (Macaca mulatta) in a manner designed to mimic the daily DHEA rhythm of young animals (5 mg of oral DHEA each morning).

Keywords: cognition, primate, steroid, brain, dehydroepiandrosterone

Chemical Strategies for Exploring Advanced Glycation End-Products

Authors: D.A. Spiegel, R. Kartika, T. Wang, T. Kim
Video: (Video)

Advanced glycation end-products are a class of natural products that form non-enzymatically on exposed protein residues in the human body. AGEs accumulate as a result of normal metabolism and aging, and significant elevations in these molecules have also been observed in the plasma of patients with chronic diseases, such as diabetes, cancer, arthritis, cardiovascular disease, and others. Our laboratory is taking an orthodox approach to studying these materials; we have initiated a synthetic program to prepare AGE- adducts on large scale and in chemically homogenous form.

Keywords: glycation, methylglyoxal, hydroimidazolones, AGEs,

Anti aging oligos 5'-(TTAGGG)n-3' treatment maintaining telomere length in vitro in human skin cells overcoming senescence and the t-loop deletion factor

Authors: W.V. Stoyanov

Telomere shortening is thought to play a role in cellular aging contributing to human aging and longevity. Critical telomere shortening affects different genes, as the human genome varies, which is why the cascades differ, hence the different effects and organ failures. For years telomere length maintenance has been targeted. However there was no one treatment to keep the length within the normal limits. Variations of telomere shortening occur within same type of tissue, as well as different tissue types, from same and different individuals.

Keywords: Telomere/s maintenance, Anti Aging, 5'-(TTAGGG)1-50-3' Oligos Treatment, T-loop deletion factor, human skin cells

Last Economic Recession Was Good for Life Expectancy

Authors: E. Taidre, Ü. Kristjuhan

Economic growth and a good economy are usually considered prerequisites for good health. Factually, the relationship of economic growth with life expectancy is complicated. Economic growth is connected with using human resources, sometimes with stress, with some wear-and-tear of the human body. Traditional and mostly acceptable workloads can be too high for some workers. Therefore, generally low economic activity can be good for public health. There have been studies of the influence of economic recessions on health and life expectancy.

Keywords: economic recession, health, life expectancy, ,

The impact of PNPASE on the therapeutic potential of mitochondrial RNA import

Authors: E. Shimada, G. Wang, C.M. Koehler, M.A. Teitell
Video: (Video)

A decline in the function of mitochondria may contribute to the aging process and age-related disorders. A functional decline could arise from accumulated mtDNA mutations over time, leading to reduced oxidative phosphorylation and other untoward effects on mitochondrial activities. Strategies that restore mitochondrial function could potentially offset key aspects of aging decline.

Keywords: PNPASE, mitochondria, RNA import, ,

Increased damage to proteins in ageing – wear and tear potentially avoidable by extending preventive maintenance of life’s essential machinery

Authors: P.J. Thornalley, N. Rabbani
Video: (Video)

Proteins undergo continual spontaneous modifications in physiological systems leading to change in their structure and function. This increases with age. Proteins are modified by glycation, oxidation and nitration leading to formation of glycation, oxidation and nitration adducts residues in proteins – including formation of non-disulfide crosslinks. Damaged proteins undergo proteolysis to form glycated, oxidised and nitrated amino acids or free adducts that are then metabolised or excreted.

Keywords: Protein damage, Glycation, Oxidative stress, Proteolysis, Systems biology

Aging Theories: a new perspective

Authors: L.S. Trindade, A. Balduino, J. Heddle

In 1881, Weismann was the first researcher to propose a reason and a mechanism by which aging occurs. He proposed death was adapted as a program to eliminate older individuals. The view that aging could be programmed and evolved by natural selection is strongly rejected by most of the scientific community. Thus, different aging theories have been developed cautiously so as not to be classified as adaptive-programmed aging. Most researchers, if not all, classify any theory that does not evoke a program for death/aging as non-adaptive.

Keywords: Aging, Evolution, oxidative damage, programmed death,

D3 – an orally applicable and potent Aβ oligomer neutralizing substance

Authors: S.A. Funke, T. van Groen, I. Kadish, D. Bartnik, L. Nagel-Steger, O. Brener, A.H.C. Horn, H. Sticht, D. Willbold

Not only Aβ fibrils, but also small soluble Aβ oligomers in particular are suspected to be the major toxic species responsible for Alzheimer’s disease (AD) development and progression. The aim of the study was to identify peptides consisting of the D-enantiomeric amino acids (D-peptides) that bind highly specific to Aβ(1-42) oligomers. D-peptides are thought to be protease resistant and less immunogenic than the respective L-enantiomers and can easily be identified by mirror image phage display.

Keywords: Alzheimer's disease, amyloid-β, therapy, peptides,

Trans-BBB exosomes

Authors: M.J.A. Wood
Video: (Video)

Successful delivery of macromolecular therapeutic agents across the blood brain barrier (BBB) to the central nervous system is a major challenge in the treatment of neurological diseases of aging. Recently, the exploitation of natural nanoparticles known as exosomes has been pioneered and demonstrates their potential as therapeutic delivery vehicles. The natural macromolecular delivery and targeting properties of exosomes are well exemplified with siRNA delivery systemically to brain to target genes implicated in Alzheimer’s disease.

Keywords: exosomes, nanoparticles, blood-brain barrier, delivery mechanisms,

Comparative Interactomics of DR-Essential Genes

Authors: D. Wuttke, R. Connor, T. Craig, C. Vora, Y. Li, S. Wood, O. Vasieva, F. Tang, J.P. de Magalhães

Dietary restriction (DR), limiting certain factors in diet, without causing malnutrition, is a non-genetic intervention that delays the ageing process and extends healthy lifespan in multiple organisms from yeast to rodents. To decipher the mechanisms of DR, we established a web-accessible database (GenDR) of DR-essential genes, which if genetically altered interfere with the effect of DR to extend the lifespan in model organisms (yeast, worm, fly and mice). DR-essential gene orthologs were identified and their molecular evolution investigated.

Keywords: Dietary restriction, Molecular evolution, Network-approach, Guilt-by-association, Comparative interactomics

Decline of the nuclear factor E2-related factor 2 (nrf2) and antistress gene response in ageing and strategies to prevent it for healthy ageing

Authors: M. Xue, N. Rabbani, P.J. Thornalley

Ageing is associated with accumulation of damaged proteins, decline in glucose tolerance, dyslipidaemia, oxidative stress, inflammatory disorders and increased cell senescence. The endogenous defence to protein damage, metabolic stress, inflammation and oxidative stress is coordinated by nuclear factor E2 related factor 2 (nrf2), kelch-related ECH protein-1 (keap1) and antioxidant response element (ARE) linked gene expression in the antistress gene response. The nrf2/keap1/ARE transcriptional system regulates the expression of a battery of protective genes.

Keywords: nrf2, Antistress gene response, Oxidative stress, Dyslipidaemia, Dietary bioactives

Is Accelerated Wound Healing Good for Longevity?

Authors: H. Yanai, R. Tacutu, D. Taranukha, A. Budovsky, V.E. Fraifeld

Wound healing (WH) is a fundamental biological process. Does the ability to heal faster have any impact on longevity? In an attempt to answer this question, we compared the established mouse models with genetically modified life span and also an altered rate of WH. Our analysis showed that the ability to preserve the rate of skin WH up to an old age, but not a high WH rate in the youngs, appears to be associated with a longevity phenotype.

Keywords: Wound healing, Longevity, αMUPA mice, ,

The integrated biomarkers and systemic targets for clinical use of anti-aging regulatory programs.

Authors: T.S. Nurgozhin, A.E. Gulyayev, Y. Yantsen, B.A. Yermekbayeva, Z.S. Zhumadilov

Current research is focused on the development of the integrated biomarkers’ system and anti-aging regulatory programs. The main target systems are immune, neuroendocrine, hepatobiliary and gastrointestinal. The ultimate goal of this research is to improve these systems' conditions and functions. We have revealed the usefulness of the consortium of probiotics and prebiotics for gastrointestinal tract and hepatobiliary system. In regards to immune system, DNA-protecting effect of probiotics is being analyzed.

Keywords: anti-aging, probiotics, , ,

Creation of Functional Ovarian Tissue

Authors: S. Joo, S. Sivanandane, J.M. Saul, J. Jackson, A. Atala, E.C. Opara, J.J. Yoo

The human ovary is the female reproductive organ containing cells that secrete hormones (estrogen, progesterone), which maintain female sexual characteristics as well as egg (ovum) production. Loss of ovarian tissue function due to various endocrine and fertility disorders requires chronic estrogen (E) and progesterone (PG) administration. Conventional hormone replacement therapy is based on oral, injection and transdermal (skin patch) administration but these have several disadvantages, such as frequent administration, fluctuation in blood hormone levels and associated complications.

Keywords: Ovary, Female hormones, Endocrine function, Follicles,

High Penetration Aspirin Pro-drug and its Application in Longevity, Anti-Diabetes, and Anti-Strokes

Authors: C. Yu
Video: (Video)

The Aspirin pro-drug aspirinamine penetrates skin, blood-brain, blood-milk, and other membrane barriers thousands of times faster than aspirin. Aspirinamine has shown a very strong anti-diabetic (both type I and type II) activity in NOD and STZ mouse models, and exerts neuroprotective effects after stroke.

It increased the maximal life span of C57BL/6 mice by 26% (at dose of 15mg/kg, equal to 10mg/kg of aspirin) and 27% (at dose of 45mg/kg, equal to 30mg/kg of aspirin).

Keywords: Aspirin, pro-drug, longevity, anti-diabetes, anti-stroke

AgingPortfolio.Org knowledge management system for aging research

Authors: A. Zhavoronkov

Aging research spans many areas of natural and social and behavioural sciences. Few data repositories aggregate data from the scientific literature, clinical trials databases, patents and grant application reports. To address this issue, we developed a flexible open-access knowledge management system for aging research the International Aging Research Portfolio (IARP) accessible via www.agingportfolio.org.

Keywords: aging research, aging database, aging system, gerontology system, knowledge management

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