One’s ability to identify different smells may impact longevity

Original Article Here Via EurekaAlert!

In a recent study of older adults, those with a reduced ability to identify certain odors had an increased risk of dying during an average follow-up of 4 years. The mortality rate was 45% in participants with the lowest scores on a 40-item smell test, compared with 18% of participants with the highest scores.

The study included 1169 Medicare beneficiaries who scratched and sniffed individuals odorant strips and chose the best answer from 4 items listed as multiple-choice.

“The increased risk of death increased progressively with worse performance in the smell identification test and was highest in those with the worst smelling ability, even after adjusting for medical burden and dementia,” said Dr. Davangere Devanand, lead author of the Annals of Neurology study. “This was a study of older adults–the question that remains is whether young to middle-aged adults with impaired smell identification ability are at high risk as they grow older.”

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Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Change to Site – Forums Gone – Papers Added

The forum section of the site has not yet taken off the way I had hoped. Also, when I switched hosts, I lost some of the more aesthetically pleasing attributes on the forum. I have also come to realize the site could benefit from a collection of published anti-aging papers. I have decided to replace the forum with this repository. I will return to the forum in the future.

`jonathon

Dr. João Pedro Magalhães SPOTLIGHT

Bio From His Personal Website Here  – His Lab Can Be Found Here  – His Twitter Here

In Addition to this spotlight, permanent links can now be found on our links page.

Dr. João Pedro Magalhães

I am originally from Porto in Portugal but have lived in Belgium and in Boston in the US, and I’m also of Spanish ancestry. Professionally, and following training at Harvard Medical School, I am now a Senior Lecturer (equivalent to an Associate Professor) at the University of Liverpool in England. My lab studies aging and longevity, in particular at the genetic level. As detailed on my senescence.info website dedicated to the biology of aging, I would ultimately like my work to help people live longer, healthier lives by contributing to retard, stop or reverse human aging. I have published dozens of scientific papers, including in top journals (e.g.,Nature– and Cell-family journals), and have given over 100 invited talks, including a TEDx talk. My research and I have been widely featured in scientific outlets (Science, Scientific American,New Scientist, etc.) and in the popular press (BBC, CNN, the Washington Post, the Financial Times and many others). I am also an advisor/consultant for various organizations, including nonprofit foundations and biotech companies. My academic work is further described on my lab’s website. I live in Heswall, Wirral, United Kingdom.

I think the human condition is only the beginning of the extraordinary journey of the mind through the universe. Technologies like genetic engineering, stem cells, cybernetics, and nanotechnology will allow us to ‘hack’ biology and evolve beyond our current human limits. As such, I am a so-called “transhumanist” in that I defend that humankind stands a better chance of survival if we understand and employ technology rather than if we try to ban it. I’m also an atheist with a life philosophy merging humanism, utilitarianism, and objectivism. May the dreams of today become the future.

Music is one of the greatest joys in my life. I started to play guitar in high school and in 1999 made a symphonic metal demo-album entitled The Legend of Hrothgar. All my songs are available for download in MP3 format.

I’m also an amateur stand-up comedian. You can find some of my older humor attempts in my news satire and cartoons sections, though nowadays I tend to use more Facebook and Twitter for this.

Among my other hobbies, I must highlight science fiction and football.

Please browse around my website to learn more about me, follow me on Twitter for the latest news, or skim through the FAQs. I am always open to suggestions, ideas, and criticisms, so please feel free to contact me.

How Old Are You, Really? Biological Age Is Harder to Pin Down Than You Think

BY  ON JAN 24, 2016

Original Article Here

In less than a month, I’ll be leaving my roaring 20s behind.

Like anyone crossing into a new decade of life, it feels surreal. I don’t look 30. I don’t feel 30. My health is better than it’s ever been. I tell my doctors I’m hitting the big 3-0 simply because that’s what the calendar — my only yardstick for the passage of time — is telling me.

how-old-are-you-really-31But what if there’s a better measure for age? A number that reflects how well your body is functioning as a whole, that predicts how rapidly you’re aging, that informs physicians when to expect medical issues, that aids the search for anti-aging therapies?

That number is a person’s biological age.

Scientists are increasingly making the distinction between your chronological age — the number of years that you’ve lived — and your biological age.

It’s not just an academic curiosity. A 2015 study, which comprehensively analyzed the function of multiple body systems of nearly 1,000 young adults, found that a 38-year-old’s biological clock can read anywhere from a spritely 20 to a feeble 60.

Even more frightening is this: although none of the participants had overt health issues, some were aging three times faster than expected.

Most people think aging happens only later in life, but — not to be macabre — our life expectancy clocks are constantly ticking down, said first author Dan Belsky, a researcher at the Duke University Center for Aging.

If we want to prevent age-related disease, we’re going to have to start treatments young, he explained. The problem is: what is “young”? How do we tell a person’s true biological age?

It’s a surprisingly hard question to answer.

Belsky took the clinical route, repeatedly giving their participants the ultimate full body workup over multiple years.

His team measured the function of the liver, kidney, heart and immune system. They tracked metabolic rate, cholesterol levels, aerobic fitness and lung function. They measured memory, reasoning and creativity. They even looked at the length of telomeres — protective “caps” at the end of chromosomes that safeguard our DNA and chip away with age.

Using these data, the team was able to construct a monster algorithm that calculates a person’s biological age and predicts the pace of deterioration.

The study made waves, and for good reason: for the first time, scientists are able to quantify aging in a younger population before the first hint of diabetes, Alzheimer’s or other age-related diseases appears. Imagine if your biological age is 10 years older than what you expected, said Belsky. It’s like a tap on the shoulder, letting you know that you need to exercise, to try caloric restriction and take better care of yourself.

Yet Belsky stresses that his study is proof-of-concept only. It took years and a fortune, he laughed. For a test for biological age to go mainstream, we need “better, faster and cheaper” markers and methods.

The dream is to take a sample of your skin or blood and tell you what your biological age is, much like a saliva sample sent to 23andMe can tell you (among other things) what kind of earwax you have.

While researchers still disagree on what constitutes a good marker, recent advances have yielded a group of candidates.

All are related to molecular processes that correlate with aging.

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Chromosomes are capped with repeating nucleotide sequences called telomeres that get shorter over time.

Discovered in the 1980s, telomeres are extra ATCG bits that trail off the end of chromosomes. Every time a cell divides, telomeres get chopped shorter, until they reach a critical length and prohibit the cell from dividing further. Subsequent population-wide studies found correlationsbetween telomere length, disease and mortality, further increasing its worth as a marker for biological age.

 

 

Backed by decades of research and a Nobel Prize, telomere length — a measure in Belsky’s study — is perhaps the leading candidate.

Scientists and investors alike have taken notice.

In 2010, Elizabeth Blackburn, one of the discoverers of telomeres, started a company in Menlo Park, California that provides analyses of telomere length from a person’s saliva sample. Life Length, a startup based in Madrid, claims to calculate a person’s biological age by the median length of their telomeres — if you’re willing to shell out $395 a pop.

Geron, another Silicon Valley company initially backed by Blackburn’s protégé, Carol Grieder, promised substantial clinical benefits of its telomere tests before abruptly switching gears. It now focuses on cancer therapies, and Grieder has long left her role as advisor to the company.

Geron’s switch away from telomere-based aging assays is telling. Telomere tests are fast, easy and cheap, but there’s one problem — they don’t particularly reflect age accurately when it comes to each individual person.

Honestly, the value of such tests is their “cocktail party” appeal, said Jerry Shay, a biologist at the Texas Southern Medical Center and advisor to Life Length. The variation in telomere length among people of the same age is huge, he explains. Besides, longer is not always better — recent studies have revealed a tradeoff between long telomeres and a higher risk of cancer.

Despite these caveats, telomere length still remains a highly valuable marker. “There’s going to be a huge amount of heterogeneity in any marker,” said Grieber. Telomeres are just part of the puzzle — the question is, what other markers can help complete the puzzle?

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Human red blood cells.

Eline Slagboom, a molecular epidemiologist at Leiden University in the Netherlands, has her money on blood.

Blood provides oxygen vital nutrients to every tissue in our body and in turn receives their waste products. We’ve known for years that the levels of some types of waste go up with age and correlate with declining organ function, said Slagboom.

For example, a 2011 study from Tony Wyss-Coray and Saul Villeda, then at Stanford University, found that injecting a young mouse with blood collected from an aged mouse throttles its brain function. Subsequent studies also showed negative effects of old blood on the liver and heart of younger recipients.

There’s a wealth of information hidden in blood, said Slagboom. Her team is running a massive study of 3,500 people aged between 40 to 110, looking at molecules in the blood that associate with age-related diseases, including cardiovascular health, dementia, diabetes and depression.

Slagboom and others’ efforts have already led to several pro-aging candidates.

Surprisingly, many are linked to the body’s immune function, which goes into overdrive with age. One candidate, with the unwieldy name of alpha1-acid-glycoprotein, is known to increase with age and independently predicts a higher risk for mortality. Another, B2M (beta-2-microglobulin), floods the body in old age and disrupts learning and memory.

Without a doubt, the race for identifying pro-aging (and pro-youth) factors is heating up.

Earlier last year, Wyss-Coray snapped up $50 million to fund his startup Alkahest, which hopes to reverse brain deficits by inhibiting pro-aging factors that accumulate with age. Although focuses on developing blood-based therapies, it’s not hard to imagine that the slew of pro-youth and pro-aging factors it uncovers could be used to measure a person’s biological age.*

In the end, no single factor — telomere, alpha1-acid-glycoprotein, B2M or other harder to measure markers such as DNA and protein damage — can paint a complete picture of a person’s true age. It’ll take multiple factors and a lot of trial and error.

But the stakes are sky high; for startups in the game of measuring biological age, literally so.

Objective age-related markers could push the anti-aging field into a whole new era, said Luigi Fontana at Washington University. They give us a way to test promising anti-aging drugs such as rapamycin andmetformin using short-term clinical trials. Instead of decades, we could be looking at months.

I can’t stress this enough, said Fontana. Knowing someone’s biological age is “very, very important.”


* Disclosure: The author works as a postdoctoral researcher with Dr. Saul Villeda, an advisor to Alkahest, at UCSF to study pro-youth factors in young blood.

Image Credit: sergign/Shutterstock.comunderworld/Shutterstock.comAJC ajcann.wordpress.com/FlickrCC; MdougM/Wikimedia Commons

Gene thought to suppress cancer may actually promote spread of colorectal cancer

Original Source Here Via EurekAlert!

UNIVERSITY OF MISSOURI-COLUMBIA

COLUMBIA, Mo. (Jan. 4, 2016) – A gene that is known to suppress the growth and spread of many types of cancer has the opposite effect in some forms of colorectal cancer, University of Missouri School of Medicine researchers have found. It is a finding that may lay the foundation for new colorectal cancer treatments.

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IMAGE: UNIVERSITY OF MISSOURI SCHOOL OF MEDICINE RESEARCHER SHARAD KHARE, PH.D., FOUND THAT A GENE THAT IS KNOWN TO SUPPRESS THE GROWTH AND SPREAD OF MANY TYPES OF CANCER HAS THE… view more CREDIT: JUSTIN KELLEY/MU

“The gene known as Sprouty2 has previously been shown to protect against metastasis, or the spreading of cancer to other parts of the body, in breast, prostate and liver cancer,” said Sharad Khare, Ph.D., associate professor of research in the MU School of Medicine’s Division of Gastroenterology and Hepatology and lead author of the study. “However, our recent molecular studies found that this gene may actually help promote metastasis instead of suppress it.”

For more than three years, Khare studied Sprouty2 in cancer cell models, mouse models and human biopsy samples. Using different molecular methods, the researchers found that the gene functions differently in colorectal cancer than in other types of cancers. Sprouty2 is known to block molecular circuits to prevent cancer cells from growing and spreading to other parts of the body. However, the researchers found that in colorectal cancer, Sprouty2 may increase the metastatic ability of cancer cells instead of suppress it. Khare believes this occurs when the gene is up-regulated, or supercharged.

Cancer deaths attributed to colorectal cancer are mainly due to tumor recurrence and metastasis to other organs. Excluding skin cancers, colorectal cancer is the third most common cancer diagnosed in both men and women in the United States, according to the American Cancer Society. It’s estimated that the lifetime risk of developing colorectal cancer is about 1 in 20.

“This finding is a very significant step in our understanding of metastasis in colorectal cancer, but it’s important to note that we believe this phenomenon may occur in only a subset of colorectal cancer patients,” Khare said. “We don’t yet know why this is the case, but we hope to determine if there is a correlation between the up-regulation of this gene and the life expectancy of patients with colorectal cancer. Future studies will help us understand who may be at risk, and ultimately, if personalized treatments can be planned to target this gene.”

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The study, “Atypical Role of Sprouty in Colorectal Cancer: Sprouty Repression Inhibits Epithelial-mesenchymal Transition,” recently was published in the cancer research journalOncogene. Research reported in this publication was supported by the National Institutes of Health under award numbers CA150081 and DC010387, Veterans Affairs Merit Award 1171590, the MU Research Board Award and MU School of Medicine Bridge funding. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Personallity Profile – Dr. Cynthia Kenyon – Google Calico

Dr Kenyon’s work with C. elegans is my oldest memory of anti-aging related research. She has had a wonderful career and now works with what I consider a dream job. Googles Calico. Here is her bio straight from their website.

Dr Cynthia KenyonGoogle Calico Cynthia Kenyon, Ph.D.

Vice President, Aging Research

Cynthia Kenyon is one of the world’s foremost authorities on the molecular biology and genetics of aging and life extension. She is Calico’s vice president of aging research.

In 1993, Kenyon’s pioneering discovery that a single-gene mutation could double the lifespan of healthy, fertile C. elegans roundworms sparked an intensive study of the molecular biology of aging. Her findings showed that, contrary to popular belief, aging does not “just happen” in a completely haphazard way. Instead, the rate of aging is subject to genetic control: Animals (and likely people) contain regulatory proteins that affect aging by coordinating diverse collections of downstream genes that together protect and repair the cells and tissues. Kenyon’s findings have led to the realization that a universal hormone-signaling pathway influences the rate of aging in many species, including humans. She has identified many longevity genes and pathways, and her lab was the first to discover that neurons, and also the germ cells, can control the lifespan of the whole animal.

cynthia kenyon

Kenyon graduated valedictorian in chemistry from the University of Georgia in 1976. She received her Ph.D. from MIT in 1981 and was a postdoctoral fellow with Nobel laureate Sydney Brenner in Cambridge, England. In 1986 she joined the faculty of the University of California, San Francisco, where she became the Herb Boyer Distinguished Professor and an American Cancer Society Professor, before joining Calico in 2014. Kenyon is a member of the U.S. National Academy of Sciences, the Institute of Medicine and the American Academy of Arts and Sciences, and she is a former president of the Genetics Society of America. She has received many scientific honors and awards.

Personallity Profile – Dr. David Sinclair – Harvard

Been following Dr. David Sinclair’s work for quite sometime, and although I have not mentioned it as much on here thus far. That changes starting now, for his work was just as influential in my dedication to Anti-Aging science as anyone’s. Thank you Dr. Sinclair.

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Via Harvard.edu  David Sinclair, Ph.D.

David Sinclair, Ph.D. is Co-Director of the Paul F. Glenn Center for the Biology of Aging, a Professor of Genetics at Harvard Medical School, Associate Member of the Broad Institute for Systems Biology, and co-founder of Sirtris Pharmaceuticals, Waltham, MA. Dr. Sinclair’s research aims to identify conserved longevity control pathways and devise small molecules that activate them, with a view to preventing and treating diseases caused by aging. His lab was the first to identify small molecules called STACs that can activate the SIRT pathway and extend lifespan of a diverse species. They also discovered key components of the aging regulatory pathway in yeast and is now focused on finding genes and STACs that extend the healthy lifespan of mice.

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Dr. Sinclair obtained a BS with first-class honors at the University of New South Wales, Sydney, and received the Commonwealth Prize for his research. In 1995, he received a Ph.D. in Molecular Genetics and was awarded the Thompson Prize for best thesis work. He worked as a postdoctoral researcher with Dr. Leonard Guarente at M.I.T. being recruited to Harvard Medical School at the age of 29. Dr. Sinclair has received several additional awards including a Helen Hay Whitney Postdoctoral Award, and a Special Fellowship from the Leukemia Society, a Ludwig Scholarship, a Harvard-Armenise Fellowship, an American Association for Aging Research Fellowship, and is currently a New Scholar of the Ellison Medical Foundation. He’s also won the Genzyme Outstanding Achievement in Biomedical Science Award for 2004.

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Direct Contact

Harvard Medical School
Department of Genetics
77 Avenue Louis Pasteur
Boston MA 02115 USA
Telephone: (617) 432-3931
Fax: (617) 432-6225
Email:
Lab Website: http://genetics.med.harvard.edu/sinclair/

Selected Publications

Howitz, KT., Bitterman, KJ., Cohen, HY., Lamming, DW., Lavu, S., Wood, JG., Zipkin, RE., Chung P., Kisielewski, A., Zhang, L., Scherer, B., Sinclair DA. (2003) Small molecule sirtuin activators that extend S. cerevisiae lifespan.Nature, 425:191-196 PMID: 12939617

Cohen, HY, Miller, C, Bitterman, KJ, Wall, NR, Hekking, B, Kessler, B, Gorospe, M, de Cabo, R.,Sinclair, DA. (2004) Calorie restriction promotes cell survival by inducing SIRT1. Science, 305:390-2. PMID:15205477

Wood, J, Rogina, B, Lavu, S, Howitz, KT, Helfand, SL, Tatar, M, Sinclair, DA. (2004). Sirtuin activators mimic calorie restriction and delay aging in metazoans. Nature, 430:686-9. PMID:15254550

Lamming, D, Latorre-Esteves, M, Medvedik, O, Wong, S.N., Tsang, F.A, Wang, C, Lin, S-J, Sinclair, DA (2005) HST2mediates SIR2-independent lifespan extension by calorie restriction. Science, 309(5742):1861-4. PMID:16051752

Baur, J, Pearson, K., 25 authors, deCabo, R, Sinclair, DA. (2006) Resveratrol increases health and survival of mice on a high calorie diet. Nature 444(16): 337-342. PMID:17086191

Yang, HY, Baur, J and Sinclair DA. (2007) Design and synthesis of SIRT1 activators that extend yeast lifespan. Aging Cell, 6(1):35-43. PMID:17156081

Milne, J., Sinclair, D., Olefsky, J., Jirousek, M, Westphal, C. (2007) Novel Small Molecule Activators of SIRT1 as Therapeutics for Treatment of Type 2 Diabetes. Nature, 450(7170):712-6. PMCID: PMC2753457

Yang, HY, Yang, T, Baur, JA, Perez, E, Matsui, T, Carmona, JJ, Lamming, DW, Souza-Pinto, NC, Bohr, VA, Rosenzweig, A, de Cabo, R, Sauve, AA, Sinclair, DA. (2007) Nutrient-regulated NAD+ levels in mitochondria dictate cell survival. Cell, 130(6):1095-107. PMC336668

Firestein, RA, Blander, G. and Michan, S., Bhimavarapu, A, Luikenhuis, S., de Cabo, R., Hahn, WC, Guarente, LP, and Sinclair, DA. (2008) SIRT1 is a tumor suppressor in a model of colon cancer. 2008; PLoS One, 3(4):2020

Pearson, K*, Baur, J*, Lewis, KN, Peshkin, L, Price, NL. Navas, P., Ingram, D., Wolf, N., Ungvari, Z, Sinclair, DA*, de Cabo, RA* (2008). Resveratrol delays age-related deterioration and mimics aspects of dietary restriction in mice on a standard diet. CellMetabolism, 8(2):157-68. PMC2538685

Oberdoerffer, P., Michan, S. McVay, M. – 8 authors – Mills, K., Bonni, A., Yankner, B., Scully, R., Prolla, TA., Alt, FW. and David A. Sinclair, D. (2008). DNA damage-induced alterations in chromatin contribute to genomic integrity and age-related changes in gene expression. Cell,135(5):907-18. PMCID: PMC2853975

Minor, R., Baur, J, Gomes, A., Price, N., Hubbard, B., Westphal, C., Ellis, J., Vlasuk, G., Sinclair, D.A. deCabo, R. (2011) SRT1720 improves survival and healthspan of obese mice. Nature Reports 1, 70. PMC3216557

Ramadori, G., Fujikawa, T., Anderson, J., Berglund, E.J., Frazao, R., Michan, S., Vianna, C., Sinclair,D.A., Elias, C. and Coppari. R. (2011) SIRT1 deacetylase in SF1 neurons protects against metabolic imbalance. Cell Metabolism, 14(3):301-12 PMC3172583

Price, N.L., Gomes, A.P., Ling, A.J., Martin-Montalvo, A, North, B.J., Hubbard, B.P., Agarwal,B. Davis,J., Varamini, B. Hafner, A., Rolo,A., Palmeira,C.M., de Cabo,R., Baur,J., and Sinclair, D.A. (2012) SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metabolism, 15(5): 675-0 PMC2538685

Escande, C., Nin, V., Price, N., Capellini, V., Gomes, A., Barbosa, M.T., O’Neil, L., White, T.A, Sinclair, D.A., Chini, E.N. (2012) The flavonoid apigenin is an inhibitor of the NAD+ase CD38. Diabetes, 62(4):1084-93. PMID: 23172919

Han, J., Hubbard, BP., Lee, J., Montagna, C., Lee, HW., Sinclair, DA., and Suh, Y. (2013) Analysis of 41 cancer cell lines reveals excessive allelic loss and novel mutations in the SIRT1 gene. Cell Cycle, epub. Jan 15. PMID: 23255128

Armour, SM., Bennett, EJ., Braun, CR., Zhang, XY., McMahon, SB., Gygi, SP., Harper, JW., and Sinclair, DA. (2013). A high-confidence interaction map identifies SIRT1 as a mediator of acetylation of USP22 and the SAGA coactivator complex. Molecular Cell Biology, 33(8):1487-502. PMID: 23382074.

Hubbard, BP., Gomes, AP., Dai, H., Li, J., Case, AW., Considine, T., Riera, TV., Lee, JE. E, Sy., Lamming, DW., Pentelute, BL., Schuman, ER., Stevens, LA., Ling, AJ., Armour, SM., Michan, S., Zhao, H., et al., Hamuro, Y., Moss, J., Perni, RB., Ellis, JL., Vlasuk, GP., and Sinclair, DA. (2013). Evidence for a common mechanism of SIRT1 regulation by allosteric activators. Science, Vol. 339: 1216-1219. PMID: 23471411

Biason-Lauber, A., Boni-Schnetzler, M., Hubbard, BP., Bouzakri, K., Brunner, A., Cavelti-Weder, C., Keller, C., Meyer-Boni, M., Meier, DT., Brorsson, C., et al., Sinclair, DA., and Donath, MY. (2013) Identification of a SIRT1 mutation in a family with type 1 diabetes. Cell Metabolism, PMID: 23473037

Lai, L., Yan, L., Gao, S., Hu, CL., Ge, H., Davidow, A., Park, M., Bravo, C., Iwatsubo, K., Ishikawa, Y., Auwerx, J., Sinclair, DA, Vatner, SF., and Vatner, DE. (2013) Type 5 adenylyl cyclase increases oxidative stress by transcriptional regulation of manganese superoxide dismutase via the SIRT1/FoxO3a pathway. Circulation, PMID: 23526361

Sinclair, DA. (2013) Studying the Replicative Life Span of Yeast Cells in Biological Aging. Ed. Trygve Tollesbol. Springer, NY, USA.Hubbard BP, Loh C, Gomes AP, Li J, Lu Q, Doyle TL, Disch JS, Armour SM, Ellis JL, Vlasuk GP, Sinclair DA. (2013) Carboxamide SIRT1 inhibitors block DBC1 binding via an acetylation-independent mechanism.Cell Cycle. 20;12(14). PMID: 23797592

Tilly, JL. and Sinclair, DA. (2013) Germline energetics, aging, and female fertility. Cell Metabolism, 17(6):838-50. NIHMS 482422

Martin-Montalvo, A., 23 authors, Sinclair, D.A., Wolf, N.A., Spindler, S., Bernier, M. and de Cabo, R. (2013) Metformin improves healthspan and lifespan in mice. Nature Communications, in press

Chen, J., Michan, S., Juan, A., Hurst, CG, Hatton CJ, Pei, DT, Joyal, J, Evans, LP, Cui, Z, Stahl, A., Sapieha, P, Sinclair, DA, Smith, LEH. (2013) Neuronal sirtuin1 mediates retinal vascular regeneration in oxygen-induced ischemic retinopathy. Angiogenesis, in press.

Hua, J., Guerin, K., Chen J., Michan, S., Stahl, A., Krah, N., Seaward, M., Dennison, R., Juan, A., Hatton, C., Sapieha, P., Sinclair, D.A., Smith, L. (2013) Resveratrol inhibits pathological retinal neovascularization in vldlr-/-mice. Angiogenesis, in press.

Schmeisser, K., Mansfeld, J., Kuhlow, D., Weimert, S., Zarse, K., Prieve, S., Heiland, I. Birringer, M., Groth, M., Segref, A., Werner, C., Schmeisser, S., Schuster, S., Pfeiffer, A., Guthke, R., Platzer, M., Hoppe, T., Cohen, C., Sinclair, D.A., Ristow, M. (2013) Theniacin metabolite 1-mthylnicotinamide extends lifespan in a PARP/sirtuin-dependent manner by including a transient redox signal. Nature Chemical Biolog in press.

Santos Franco S, De Falco L, Ghaffari S, Brugnara C, Sinclair DA, Mattè A, Iolascon A, Mohandas N, Bertoldi M, An X, Siciliano A, Rimmelé P, Cappellini MD, Michan S, Zoratti E, Janin A, De Franceschi L. Resveratrol accelerates erythroid maturation by activation of FOXO3 and ameliorates anemia in beta-thalassemic mice. 2013.Haematologica. Aug 23

Hubbard BP and Sinclair DA. Measurement of sirtuin enzyme activity using a substrate-agnostic fluorometric nicotinamide assay. Methods Mol Biol. 2013;1077:167-77

Sinclair DA. Studying the replicative life span of yeast cells. Methods Mol Biol. 2013;1048:49-63.

Chen J, Michan S, Juan AM, Hurst CG, Hatton CJ, Pei DT, Joyal JS, Evans LP, Cui Z, Stahl A, Sapieha P, Sinclair DA, Smith LE. Neuronal sirtuin1 mediates retinal vascular regeneration in oxygen-induced ischemic retinopathy.Angiogenesis. 2013;16(4):985-92

Sinclair D.A. and Guarente, L. Small molecule activators of sirtuins for the treatment of age-related diseases. Annual Revews Phramacol. Sci. 2013. 54:363-80.

Hubbard and Sinclair, D.A. Small molecule sirtuin activators. J. Experimental Medicine (2013) In press.

Hubbard BP, Sinclair DA. Measurement of sirtuin enzyme activity using a substrate-agnostic fluorometric nicotinamide assay. Methods Mol Biol. 2013, 1077:167-77.

Sinclair D.A. and Guarente, L. Small molecule activators of sirtuins for the treatment of age-related diseases.Annual Revews Pharmacol. Sci. (2013) 54:363-80.

Hubbard and Sinclair, D.A. Small molecule modulators of sirtuins. Trends in Pharmacol Sci (2014), in press.

Michan, S., Juan, A.M., Hurst, C.G., Cui, Z., Evans, L.P., Hatton, C.J., Pei, D.T., Ju, M., Sinclair, D.A., Smith, L.E.H., Chen, J. Sirtuin1 over-expression does not impact retinal vascular and neuronal degeneration in a mouse model of oxygen-induced retinopathy. PLoS One 2013, 9(1):e85031.

Strong R, Miller RA, Astle CM, Baur JA, de Cabo R, Fernandez E, Guo W, Javors M, Kirkland JL, Nelson JF, Sinclair DA, Teter B, Williams D, Zaveri N, Nadon NL, Harrison DE. Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium-chain triglyceride oil on life span of genetically heterogeneous mice. Gerontol A Biol Sci Med Sci. 2013 68(1):6-16. PMID: 22451473

Gomes, A.P., Price N.L., Lin A.Y, Moslehi, J., Montgomery, M., Rajman, L., White, J.P., Teodoro, J.S., Wran, C.D., Hubbard, B.P., Mercken, E.M., Palmeira, C., de Cabo, R., Rolo, A.P., Turner, N., Bell, E. and Sinclair, D.A. Declining NAD+ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell 2013 155(7):1624-38.

Wu, E.W., Gomes, A.P. and Sinclair, D.A. Geroncogenesis: Metabolic changes during aging as a driver of tumorigenesis. 2014. Cancer Cell, 25:12-19

Yoon, C., Ling, A.Y., Isik, M., Lee, D.D., Steinbaugh, M.J., Sack, L., Boduch. A.N., Blackwell, T.B., Sinclair, D.A*, Elledge, S.J.* GLTSCR2/PICT1 links mitochondrial stress and Myc signaling. Proc. Natl. Acad. Sci., 2014, 111(10):3781-6.

The Sirt1 activator SRT3025 provides atheroprotection in Apoe-/- mice by reducing hepatic Pcsk9 secretion and enhancing Ldlr expression. Miranda MX, van Tits LJ, Lohmann C, Arsiwala T, Winnik S, Tailleux A, Stein S, Gomes AP, Suri V, Ellis JL, Lutz TA, Hottiger MO, Sinclair DA, Auwerx J, Schoonjans K, Staels B, Lüscher TF, Matter CM.Eur Heart J. 2015 Jan 1;36(1):51-9.

Mitchell SJ, Martin-Montalvo A, Mercken EM, Palacios HH2, Ward TM2, Abulwerdi G2, Minor RK, Vlasuk GP, Ellis JL, Sinclair DA, Dawson J, Allison DB, Zhang Y, Becker KG Bernier M, de Cabo R. The SIRT1 Activator SRT1720 Extends Lifespan and Improves Health of Mice Fed a Standard Diet. Cell Rep. 2014 Feb 25.

Mercken, EM*, Mitchell, SJ*, Martin-Montalvo, A,1 Minor, RK, Almeida, M., Gomes, A., Scheibye-Knudsen, M., Palacios, H., Licata, JJ, Zhang, Y, Becker, K.G. Khraiwesh, H., Gonzalez-Reyes, J., Villalba, JM, Baur, JA, Vlasuk, G, Ellis, JL, Sinclair, DA, Bernier, M, and de Cabo, R. SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass. Aging Cell 2014, in press

Solon-Biet SM, McMahon AC, Ballard JW, Ruohonen K, Wu LE, Cogger VC, Warren A, Huang X, Pichaud N, Melvin RG, Gokarn R, Khalil M, Turner N, Cooney GJ, Sinclair DA, Raubenheimer D, Le Couteur DG, Simpson SJ. The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice.Cell Metab. 2014 Mar 4;19(3):418-30.

North BJ, Rosenberg MA, Jeganathan KB, Hafner AV, Michan S, Dai J, Baker DJ, Cen Y, Wu LE, Sauve AA, van Deursen JM, Rosenzweig A, Sinclair DA. SIRT2 induces the checkpoint kinase BubR1 to increase lifespan. EMBO J.2014 May 12.

Rimmelé P, Bigarella CL, Liang R, Izac B, Dieguez-Gonzalez R, Barbet G, Donovan M, Brugnara C, Blander JM, Sinclair DA, Ghaffari S. Aging-like phenotype and defective lineage specification in SIRT1-deleted hematopoietic stem and progenitor cells.

Gomes AP, Sinclair DA. Measuring PGC-1α and its acetylation status in mouse primary myotubes. Methods Mol Biol.2015;1241:49-57.

Moroz N, Carmona JJ, Anderson E, Hart AC, Sinclair, DA, Blackwell TK. Dietary restriction involves NAD⁺-dependent mechanisms and a shift toward oxidative metabolism. Aging Cell. 2014 Dec;13(6):1075-85.

New SENS Laboratory at Cambridge via Philanthropist Jason Hope

Original – Fight Aging – Article Here and Original – SENS Research Foundation – Article Here

Jason Hope, you might recall, has provided half a million dollars in research funding to the SENS Research Foundation, used to establish a SENS laboratory at Cambridge in order to push forward with the Foundation’s AGE-breaker program. AGE-breakers are drugs or other treatments capable of breaking down advanced glycation end-products (AGEs). These are a class of metabolic waste product that accumulate in our tissues to cause significant harm that includes the progressive loss of elasticity in skin and blood vessels.

There is, on the whole, far too little work undertaken today on AGE-breaker treatments in comparison to the benefits that a treatment could bring. What little research has taken place over the past twenty years unfortunately produced no effective therapies. As it turned out the AGEs that are important in short-lived laboratory animals are not the same at all as those that are important in humans – something that would have been challenging to identify until comparatively recently, and which resulted in promising animal studies that then went nowhere in commercial trials.

Now, however, researchers know that the vast majority of all AGEs in human tissues consist of just one type, called glucosepane – so the way is open for bold philanthropists and forward-looking researchers to build therapies that will be effective in removing this contribution to degenerative aging. Glucospane removal is one of the areas in which the SENS Research Foundation and its backers pick up the slack, undertaking important rejuvenation research that is neglected by the mainstream, even though it was exactly the mainstream research community that produced all of the studies and evidence that demonstrate the important role of glucospane in aging.

In any case, I should point out that Jason Hope runs a website and blog in which he discusses his take on philanthropy and his support for research aimed at extending healthy human life and rejuvenating the old. This makes for an interesting follow-on from yesterday’s post on big philanthropy. More folk of this ilk would certainly be a good thing, and I’m always pleased to see more of the better connected people in this world of ours speaking openly of their support for rejuvenation biotechnology.

Philanthropy

Quote:

Philanthropy has become a big focus for me. The organizations I have chosen to stand behind have come from many facets of my life. One of my passions has become the research done at the SENS Research Foundation. Their involvement in anti aging is not just about wanting to live forever. It’s about creating a longer, better quality of life.Foundations like SENS are taking a different approach to anti-aging. They are focused on finding cures for disease that break down the body and thus cause us to age faster than we should. Disease like Alzheimer’s and heart and lung disease affect all functions of the body. Traditional medicine looks at treating these diseases after they happen. We want to focus on stopping these diseases from ever happening. We have spent so much time focused on medication for treating disease and not enough time on preventing that disease from ever happening.

By supporting scientific research that thrives through innovation and is not afraid to challenge the modern school of thought we will continue to break down walls.

A 21st Century Philanthropic Model For Philanthropy

Quote:

Can you conceive of a world without age-related disease, disability and suffering? What about a world in which it’s possible for the average person to live 120 healthy years? While it may sound like a utopian dream, such a world is the exact goal of some of society’s most brilliant scientists and visionary leaders. At this very minute, groundbreaking work is underway at universities across the globe as researchers attempt to apply regenerative medicine to age-related disease through the repair of damage to tissue, cells and molecules within the body. While this research couldn’t be possible without the leadership of the world’s wealthiest philanthropists, it also relies upon the collective power of everyday people who have joined forces in their commitment to a better quality of life for all.Traditionally, big ticket donors have been the primary target for fundraising programs. Research has consistently shown that the bulk of donor funds come from a small percentage of the wealthiest donors: in fact, a full 75 percent of funds raised come from gifts of over $1 million.

Instead of resigning themselves solely to the influence of the individual, non-profits are turning to the collective power of a group. The MFoundation’s “The 300 Pledge” fundraising campaign is an exciting example of this method in practice. The 300 Pledge asks 300 funders to commit $1,000 a year for 25 years toward critical research aimed at ending age-related diseases. When broken down, this goal is manageable for many households: just $3 a day or $85 a month – less than your daily tab at Starbucks. Obviously, the model is working: to date, 291 people have taken up the challenge, with nine spots remaining.

As evidenced by the magnificent philanthropy of people like Peter Thiel, Bill Gates and others like them, it’s obvious that one person can make a difference. However, fundraising challenges, like MFoundation’s “The 300,” also demonstrate the power of a dedicated group of people to foster real world change for the billions of people living in the world today as well as the generations that follow. In doing so, those who take up the challenge create a unique and world-altering legacy for themselves.