Accepted abstracts for SENS6

Conference: SENS6

Purification and identification of soybean antioxidant peptides by consecutive chromatography and electrospray ionization-mass spectrometry

Authors: Coauthors: Peng Liu, Mouming Zhao, Yalan Cao, Yunjun Lu, Ming Liang, Zebo Huang, Jiaoyan Ren* (Corresponding author: Jiaoyan Ren)
Ultrafiltration, ionexchange chromatography, and gel filtration chromatography techniques were performed to purify antioxidant peptide from soybean protein isolate hydrolysates (SPIH). It was found that alkaline peptides exhibited stronger antioxidant capacity than acidic or neutral peptides. As compared with larger peptides, the < 1 kDa fraction showed much higher antioxidant activity. A tripeptide, Ser-Phe-Val (352.4 Da), was finally identified using RP-HPLC connected online to an electrospray ionization mass spectrometry.The identified peptide was prepared by fluorenylmethoxycarbonyl (...
Keywords: soybean antioxidant peptide, oxygen radical absorption capacity, electrospray ionization-mass spectrometry

PANACEA broad-spectrum antiviral therapeutics

Authors: Rider TH.
Although there is great concern over emerging viruses and viruses on the category A-C priority pathogen lists, there are relatively few prophylactics or therapeutics for these viruses, and most which do exist are highly pathogen-specific or have undesirable side effects or other disadvantages.  As part of our PANACEA program, we have developed a radically new and very broad-spectrum antiviral therapeutic/prophylactic that has the potential to revolutionize the treatment of viral infections, including those due to emerging, category A-C, and common clinical pathogens.  Our Double-stranded RNA...

The disruptive potential of tissue engineering

Authors: Russell A.
Tissue engineering is one of the most exciting tools through which regenerative medicine can be accomplished.  The concept of growing neo-organs that can cure diseases versus treat symptoms is compelling.  This paper will explain why tissue engineering is a fast moving field that brings ideas to the clinic more quickly than the pharmaceutical industry.  As a disruptive technology, tissue engineering has struggled to find strong market adoption and this presentation will also summarize the existing challenges in the field and suggest routes that these barriers can be overcome.  In particular...

NAD(P)+ depletion causes mitochondrial dysfunction induced senescence

Authors: Sarnoski E.A., Velarde M.C., Campisi J.
                Cellular senescence occurs in response to various stimuli such as DNA damage and oncogene activation. Senescence is characterized by an irreversible growth arrest and is hypothesized to contribute to organismal aging. Although senescent cells are known to accumulate with age, the etiology of these cells remains controversial. We show that temporary mitochondrial dysfunction can result in senescence. We hypothesize that the stoichiometric balance of NAD+/NADH in the glycolysis-lactic acid metabolism pathway leads to NAD+ insufficiency for other cellular processes, promoting...
Keywords: mitochondria, senescence, metabolism

Utilizing B cells to recreate the biochemical environment of youth

Authors: Herbig E, Xu M, Scholz M
New proteins that affect or play a role in aging are continually being discovered.  While some of these molecules may have great potential for reversing aging and extending lifespan, current technologies for delivery of biologic proteins are costly and require frequent re-dosing to sustain therapeutic levels. Thus, the field of regenerative medicine is in need of a mechanism that can elicit long-term production of biologics in vivo in a manner that is both cost-effective and clinically practical. Immusoft is currently commercializing technology that turns a patient’s own B cells into drug...
Keywords: cell therapy, gene therapy

Chromatin and epigenetic dynamics in senescence phenotypes

Authors: Sedivy JM.
Chromatin is a complex and dynamic structure that needs to be maintained in a functional state throughout the lifetime of an organism. Studies of diverse species, including mammals, have revealed that chromatin undergoes extensive rearrangements during aging. Cellular senescence, an important component of mammalian aging, has recently been associated with decreased heterochromatinization of normally silenced regions of the genome. These changes appear to lead to the expression of retrotransposable elements (RTE), culminating in their transposition. RTEs are common in all kingdoms of life, and...
Keywords: senescence, chromatin, retrotransposable elements, RTEs

Intermittent hypoxia, oxidative stress and inflammation: The long and stressful road to cardiovascular disease

Authors: Shannack M.
Obstructive sleep apnea (OSA) is a condition of sleep-disordered breathing which is an increasing health concern due to independent associations with cardiovascular diseases. An element of OSA, called intermittent hypoxia (IH) is thought to be responsible for many of the detrimental effects of this disorder. In particular, IH is believe to induce the generation of reactive oxygen species (ROS) which leads to oxidative stress (OS), and inflammation. A combination of OS and inflammation is implicated in the development of endothelial dysfunction, hypertension and arterial stiffness; all of...

Bioinformatic analysis of factors involved in age-related mineralization of soft tissues

Authors: Shindyapina AV, Mkrtchyan G, Gneteeva T, Buiucli S, Zhavoronkov A.
Age-related metastatic mineralization of the soft tissues was historically considered to be a passive and spontaneous process. Recent data demonstrate that calcium salts deposition in soft tissues could be a highly regulated process. Mechanisms leading to this pathology vary in different patients and depend on disease type, stage, patient gender, and age. Although calcification occurs in any tissue type, vascular calcification has been of particular interest due to association with atherosclerosis, chronic kidney disease (CKD), and osteoporosis. Patients with these age-related disorders...
Keywords: Metastatic calcification, Collagen cross-linking, Vascular calcifiaction, Systematic review

Range of variation in the duration of C. elegans dauer and post-dauer survival: Food intake of parents and first-stage larvae affects adults recovered after 60 days of developmental arrest

Authors: Balasubramaniam M, Ayyadevara S, Shmookler-Reis R.
The nematode C. elegans, when maintained under crowded and/or starved conditions (or upon exposure to a hormonal mixture termed “daumone”), enter an alternative developmental stage called the dauer larva. This is a motile but non-feeding state of developmental arrest, which is considered “non-aging” because worms that resume development, after as much as 2 months in dauer status, survive as adults with the same lifespan as worms that never entered dauer [1]. Recovery diminished between 60 and 90 days of dauer arrest, and adult lifespan was not tested beyond 60 days [1]. Aubrey de Grey...
Keywords: C. elegans, dauer, calorie restriction, lifespan, survival

Screening of medicinal plants in the Judea region (Israel) for geroprotective activities

Authors: Budovsky A, Shteinberg A, Maor H, Duman O, Yanai H, Wolfson M, Fraifeld VE
Plants growing in the Judea region are widely used in traditional medicine. This phytogeographic zone stands out in its climatic conditions and biodiversity. Consequently, both endemic and widely distributed Mediterranean plants growing in the area have unique chemotypes, characterized by accumulation of relatively high levels of phytosteroids. Our comprehensive analysis revealed that many of the plants growing in the Judea region may hold a geroprotective potential. With this in mind, we undertook a wide screen of dozens of candidate herbal extracts for their cell protective, wound healing,...
Keywords: Medicinal plants, Judea region, Geroprotective activity

Aged mice repeatedly injected with plasma from young mice: a survival study

Authors: Shytikov DW, Balva OV, Pishel IM, Debonneuil E
The deterioration of functions of various organs and systems with age is well documented. Numerous violations in metabolism, in the cardiovascular system and the immune system lead to the development of specific diseases associated with aging that are the main cause of death of people in older age groups. In a classical work by Carrel et al., serum from old animals was found to inhibit the growth of cell cultures. More recently, Wyss-Corray et al. showed that injection of plasma from older animals can cause age-related changes in the nervous system of young recipients. This and other work...
Keywords: Plasma injection, Survival rate, CD4/8 ratio, Thyroxin level

ALTered cancer cells: Uncovering the genetic basis of ALT (Alternative Lengthening of Telomeres)

Authors: Halvorsen D, Hunt T, Moody K, Silva H.
As normal cells divide, the ends of their chromosomes (telomeres) progressively shorten until eventually the cells reach senescence or undergo apoptosis. Cancers, which disproportionally kill more individuals in the 65 years or above age group, often overcome this built-in replication limit by expressing the enzyme telomerase. However, about 10-15% cancers do not use telomerase and at least a major subset of these exhibit hallmarks of Alternative Lengthening of Telomeres (ALT) activity, including (1) long and heterogeneous telomere lengths, (2) presence of ALT-associated PML nuclear bodies (...
Keywords: telomeres, telomerase, ALT, cancer, genetic mechanisms

Nicolai Sietnicki - a Nicolai Fedorov follower as transhumanist precursor of a dogmatic philosophy of the extension of life concept

Authors: Sitnicki I.
Nicolai Sietnicki (1888-1937), also spelled Setnitsky, scion of Polish noble family bearing Nałęcz coat-of-arms. Born in Olgopol, Volhynia, Ukraine. After graduating from a classical gymnasium, he completed studies at Saint Petersburg Imperial University. Graduate of both law and sinology faculties, he also studied physics, mathematics and statistics. After military service in WW I, he worked in Odessa. The collapse of the Russian Empire and Bolshevik Revolution forced him to emigrate into Harbin, Manchuria, where he worked for Transsiberian Chinese Railway and later took a post as professor...

Targeted mitochondrial therapeutics in aging

Authors: Smigrodzki R, Portell RF, Onyango I, Dennis J, Khan SM
Mitochondrial dysfunction in aging consists of relative suppression of oxidative phosphorylation and  frequently an increase in glycolysis. This metabolic imbalance is triggered by progressive biochemical processes, including accumulation of mitochondrial mutations, and changes in the expression and function of nuclear-encoded mitochondrial proteins. Our group developed methods for mitigation of mitochondrial suppression through mitochondria-targeted therapeutics. We observed that stimulation of mitochondrial activity both in vitro and in vivo significantly improves cellular function,...

Life-long persistent viral infection alters the naïve T-cell pool, impairing CD8 T-cell immunity in late life

Authors: Smithey MJ, Li G, Venturi V, Davenport MP, Nikolich-Zugich J
Persistent CMV infection has been associated with immune senescence. To address the causal impact of life-long persistent viral infection on immune homeostasis and defense, we infected young mice systemically with murine CMV (MCMV) and studied their T-cell homeostasis and function over the lifespan. Upon Listeria-OVA infection, 23 month-old animals that had experienced life-long MCMV infection showed impaired bacterial control and CD8 T-cell function compared to age-matched, uninfected controls. Lifelong MCMV infection was associated with reduced naïve CD8 T-cell precursors, above the loss...

Chemical and biological approaches to understanding advanced glycation end-products (AGEs)

Authors: Spiegel DA.
Advanced glycation end-products (AGEs) are a complex class of non-enzymatic post-translational modifications of proteins that have been associated with numerous age-related health deficits.  Because they form as complex mixtures in the body, however, they have been difficult to isolate and study in chemically homogeneous form.  This presentation will focus on our laboratory’s efforts to synthesize and study chemically pure AGEs including the methylglyoxal-derived hydroimidazolones (MG-Hs) and glucosepane.  These studies have led to several novel discoveries, which have significant potential...
Keywords: Advanced Glycation End-Products (AGEs), Glycation, Post-translational modification

On the history of life-extension research: Does the whole have parts?

Authors: Stambler I
This presentation will explore the history of life-extension research in the 20th century. I will argue that the search for life-extension has often constituted a formidable, though hardly ever acknowledged, source for biomedical research and discovery, in such diverse fields as endocrinology (Steinach, 1910s-1920s); probiotic diets (Metchnikoff, 1900s); blood transfusion (Bogdanov, 1920s), systemic immunotherapy (Bogomolets, 1930s-1940s) and cell therapy, including human embryonic cell therapy (Niehans, 1930s-1950s). This presentation will briefly recapitulate some of the biomedical...
Keywords: Life extension, history of medicine, reductionism, holism, homeostasis

Transplantation of in vitro derived microglia

Authors: Stolzing A.
Alzheimer’s disease (AD) is an age-related neurodegenerative disease associated with the formation of amyloid plaques, tau aggregation and oxidative/inflammatory damage. Microglia play an important role in the early phase of the disease and are known to be involved in AD progression. Senescent microglia accumulate in AD causing inflammation, neuronal damage and increasing the Aß load. Microglia could be an attractive target for replacement/rejuvenation cell therapies. Bone marrow derived from wild type and GFP transgenic black/6 mice (~aged 3 month) was differentiated into microglia in vitro...
Keywords: Alzheimer's disease, microglia, cell therapy, differentiation, stem cells

System modeling of genetic factors that induce pluripotency

Authors: Sukhera UA, Nawaz MS.
The advent of Induced Pluripotent Stem Cells has significantly increased the pace of the research in regenerative medicine and stem cell domains. Even though much work has been accomplished but still challenges remain to find the best genes used to induce pluripotency. The objective of this research is to find out the best “cocktail” of reprogrammable factors that induce pluripotency and link them through expression pathways and in silico approaches to associate all in a simplified System model. We designed a simplified methodology based on automated literature data mining, conserved synteny...
Keywords: Induced Pluripotent Stem Cells, System Model, Pluripotency, Yamanaka Factors, Reprogrammable Factors

Prediction of new lifespan regulators in C. elegans

Authors: Tacutu R, Budovsky A, de Magalhães JP, Fraifeld VE.
Many studies in model organisms have successfully focused on identifying the genetic factors that determine lifespan and so far hundreds of longevity-associated genes (LAGs) have been discovered [1]. Yet, the search is still on. Biological processes often revolve around protein complexes and are fine-tuned by regulatory factors. As such, the first-order protein-protein interactors of known LAGs are likely to participate in the regulation of lifespan and are more likely to have longevity phenotypes than randomly chosen genes. Moreover, many of these longevity interactors are essential for...
Keywords: longevity, networks, prediction

The links between polar mRNA transport and lifespan in budding yeast Saccharomyces cerevisiae

Authors: Taranukha D, Budovsky A, Gobshtis N, Braiman A, Porat Z, Aronov S, Fraifeld VE
The budding yeast Saccharomyces cerevisiae is a unique model for studying the links between aging and rejuvenation. These two processes are coupled through specific regulatory mechanisms of the polar protein transport between the mother (aging) and daughter (rejuvenating) cell. Here, we examined a still unexplored possibility for co-regulation of polar mRNA transport and lifespan. To monitor the amount and distribution of mRNA-containing granules in mother and daughter cells, we used a fluorescent mRNA-labeling system, with MFA2 as a reporter gene. The results obtained showed that deletion of...
Keywords: Lifespan, mRNA polar transport, Budding yeast

What reassurances do the community need regarding life extension? Evidence from studies of community attitudes and an analysis of film portrayals

Authors: Underwood M, Hall W, and Bartlett H.
It is increasingly recognised that community attitudes impact on the research trajectory, entry and reception of new biotechnologies. Yet biogerontologists have generally been dismissive of public concerns about life extension. There is some evidence that biogerontological research agendas have not been communicated effectively, with studies finding that most community members have little or no knowledge of life extension research. Perhaps because of this lack of knowledge, community members’ attitudes and concerns reflect issues raised  in popular portrayals of life extension  (e.g. in...

Androgen supplementation during aging: development of a physiologically appropriate protocol

Authors: Urbanski HF
Old rhesus macaques (Macaca mulatta), like elderly humans, show a marked age-related decline in the circulating levels of dehydroepiandrosterone sulphate (DHEAS), an androgen precursor. Old males also show a significant age-related decline in circulating levels of testosterone (T).  Consequently, there is interest in developing androgen supplementation paradigms for the elderly that recapitulate the hormone profiles observed during early adulthood.  Using the male rhesus macaque animal model, we have found that supplementing old males with oral T (12 mg/kg body weight, in sesame oil/chocolate...
Keywords: testosterone, DHEA, DHEAS, estradiol, cortisol

Stem and progenitor cell senescence in aging

Authors: van Deursen, JM.
Senescent cells accumulate with aging and have been causally implicated in aging, but which cell types are subject to cellular senescence and contribute organ/tissue remains poorly understood. Mutant mice with low amounts of the mitotic checkpoint protein BubR1 accumulate large amounts of p16Ink4a positive-senescent cells in eye, skeletal muscle, and fat, at a young age and develop age-related pathologies in these tissues. Clearance of senescent cells from these animals, either by genetic inactivation of p16Ink4a or drug-induced apoptosis considerably delays premature aging. To understand the...
Keywords: senescence, p16Ink4a, senescent cells, progenitor cells

Improved technology for organ cryopreservation by vitrification

Authors: van Sickle S, Jones T.
Cryopreservation by vitrification is the current state of the art in experimental organ preservation for transplant. Unlike methods in currently clinical use which only preserve large vascular organs in transplantable condition for hours, vitrification and storage below the glass transition temperature (~-130C) would enable safe storage for years or decades. Success with organ cryopreservation by vitrification would permit true banking of organs, increasing the number available, improving immune matching, and reducing wait list times.Two major limitations to this method are thermomechanical...
Keywords: cryopreservation, organ banking, fracturing, cryoprotectant toxicity, organ transplantation

Nutraceutical properties of extravirgin olive oil: a natural remedy for age-related disease?

Authors: Virruso C, Accardi G, Colonna-Romano G, Candore G, Vasto S, Caruso C
The health benefits of the Mediterranean Diet can be largely ascribed to the nutraceutical properties of extra-virgin olive oil (EVOO). Monounsaturated fatty acids (MUFA) such as omega-3 and various phenolic compounds such as oleocanthal, oleuropein, hydroxytyrosol and tyrosol are the main nutraceutical substances of EVOO. These substances have been suggested to have the ability to modulate ageing- associated processes. In experimental models, it was shown that EVOO with high concentration of poliphenols has antiinflammatory and antioxidant properties. Indeed, it was observed that...
Keywords: Olive Oil, Inflammation, Oxidative Stress, age-related diseases

Diabetes type 2 and cancer: an integrative approach to prevention, treatment and rehabilitation.

Authors: Voronina T, Grechko N.
Diabetes type 2 (D2) and cancer have some similar characteristics in pathogenesis. D2 and cancer are misfolded protein (MPr) diseases. The main preventive actions for both should be supporting the effectiveness of mitochondria (not supplying excess of glucose and oxygen) and reducing the cellular effects of MPr (toxic, non-functional, related to infections, p53 mutation protein). Our approach combines Intermittent Caloric Restriction (ICR) and Intermittent Hypoxia Therapy (IHT), which can synchronise body functions and support the effectiveness of mitochondria. The 42 patients involved in the...
Keywords: intermittent fasting, calorie restriction, intermittent hypoxia therapy, diabetes, acupuncture

Web intelligence to solve aging

Authors: Wuttke D, Kulaga A.
Aging is a complex phenomenon that requires an engineering approach in order to be solved. We initialized the construction of a digital decipher machine, Denigma [http://denigma.de], to reverse-engineer the aging process, make aging research more collaborative as well as efficient and facilitate the discovery of powerful therapeutics. Denigma is an open-source platform that uses advanced information technologies for the creation of a web intelligence. It provides an ecosystem of domain-specific tools and applications for the establishment of a comprehensive knowledge base rendered amenable to...
Keywords: reverse-engeneering, information technology, machine-learning, crowdsourcing, web intelligence

Solving aging with web intelligence

Authors: Wuttke D, Kulaga A.
The aging process remains an Enigma, though by combining the "power of the crowd", i.e. collective human intelligence, with increasing computational power of machine intelligence we can reverse-engineer the aging process. In order to decipher the aging process, the construction of a Digital Decipher Machine, Denigma [http://denigma.de], was initialized. Denigma is an open-source project that creates a web intelligence and promotes open distributed science for longevity research. This framework results in the establishment of a comprehensive knowledge base that allows global web-scale...
Keywords: web, knowledge, reasoning, intelligence, anti-aging

Senescent cells—bad neighbors for cancer cells?

Authors: Yanai H, Tacutu R, Budovsky A, Caliò A, Chilosi M, Fraifeld VE
Since Hayflick’s discovery of the phenomenon of cellular senescence (CS), the contribution or even relevance of this phenomenon to organismal aging has been a subject for continuous debates. Although the question still remains open, an increasing amount of evidence indicates that CS could have a role in aging and age-related diseases (ARDs), rather than being just a laboratory phenomenon. In fact, the current situation in the field could be defined as an attempt to understand to what extent and how is CS involved in aging and ARDs. CS has primarily been suggested as an anti-cancer mechanism....
Keywords: Cellular senescence, Cancer, Age-related diseases

Mitochondrial quality control: links to Parkinson’s disease and aging models

Authors: Youle RJ.
The products of two genes mutated in autosomal recessive forms of Parkinson’s disease, Pink1 and Parkin, have been identified in Drosophila to work in the same pathway to maintain healthy flight muscles and dopaminergic neurons. PINK1 is a kinase located on mitochondria whereas Parkin is an E3 ubiquitin ligase normally located in the cytosol.  Upon mitochondrial damage Pink1 recruits cytosolic Parkin to mitochondria to mediate mitophagy revealing a cell biology pathway in mammalian cells where Pink1 works upstream of Parkin. Although PINK1 has a predicted mitochondrial import sequence, its...

New economic arguments for accelerating aging research

Authors: Maria Litovchenko, Alex Zhavoronkov
While the doubling of the life expectancies in the developed countries in the 20th century can be attributed mostly to decreases in child mortality, trillions of dollars spent on the biomedical research by the governments, foundations and corporations over the past sixty years are yielding longevity dividends in the older population. When increases in life span will occur after the retirement age and extend the "last mile", unless the retirement age is proactively adjusted, the net economic effect of these increases is negative. We introduced several new parameters that can be applied to the...
Keywords: aging economics, ageing economics, economics of longevity, life span economics

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