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It seems that opposition against anti-aging medicine may be slowly starting to crumble. For example, Lifespan.io’s current crowdfunding campaign is going extremely well, and journalists begin to talk about senolytics in positive terms, without any predictions of doom and gloom resulting from these upcoming drugs. Make no mistake—the pro-aging trance is still alive and well; for each journalist who puts time and effort into actually understanding senolytics and the health benefits that they are expected to bring to older people, there’s probably five who show little to no knowledge of the subject and rage against unspecified “immortality” technology and related impending catastrophes. This should tell us something about the kind of understanding they have of what they criticize—or how badly they need a clickbait piece to bring in visitors.

Today, the pro-aging trance is something that only rejuvenation advocates are aware of and battle against, but maybe, fifty years from now, it will be an interesting phenomenon of the past for psychologists to figure out. Maybe, on the YouTube of 2068, there will be videos making fun of it in pretty much the same way that some people today make fun of the old belief that hysteria was caused by stray uteruses wandering around women’s bodies.

The pro-aging trance is rather interesting indeed, as people who are subject to it tend to commit fallacies that they would never commit in other contexts. A very good example of this is the objection to inequality of access: this reasoning assumes that rejuvenation would not be available to everyone who needs it, for economical, political, or whatever reasons; understandably, this is perceived as a profound injustice, which pushes a fair number of people to make a leap and conclude that the best way to avoid this injustice is to never develop rejuvenation to begin with.

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Drugs that target multiple aging pathways at once significantly extend the healthspan and lifespan of nematodes.


In a paper published in Developmental Cell, scientists from Yale University have demonstrated how targeting multiple pathways related to aging with different drug combinations can slow aging down and extend healthy lifespan in C. elegans [1].

Abstract

There is growing interest in pharmacological interventions directly targeting the aging process. Pharmacological interventions against aging should be efficacious when started in adults and, ideally, repurpose existing drugs. We show that dramatic lifespan extension can be achieved by targeting multiple, evolutionarily conserved aging pathways and mechanisms using drug combinations. Using this approach in C. elegans, we were able to slow aging and significantly extend healthy lifespan. To identify the mechanism of these drug synergies, we applied transcriptomics and lipidomics analysis. We found that drug interactions involved the TGF-b pathway and recruited genes related with IGF signaling. daf-2, daf-7, and sbp-1 interact upstream of changes in lipid metabolism, resulting in increased monounsaturated fatty acid content and this is required for healthy lifespan extension.

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On the 23rd of this month, Dr. David Sinclair did an Ask Me Anything over at the Futurology subreddit in support of the NAD+ Mouse Project on Lifespan.io. There were a range of interesting questions from the community about his work in aging research, particularly the role of NAD+ in aging.

Dr. David A. Sinclair is a Professor in the Department of Genetics at Harvard Medical School and a co-joint Professor in the Department of Physiology and Pharmacology at the University of New South Wales. He is the co-Director of the Paul F. Glenn Laboratories for the Biological Mechanisms of Aging and a Senior Scholar of the Ellison Medical Foundation. He obtained his Ph.D. in Molecular Genetics at the University of New South Wales, Sydney in 1995. He worked as a postdoctoral researcher at M.I.T. with Dr. Leonard Guarente; there, he co-discovered a cause of aging for yeast as well as the role of Sir2 in epigenetic changes driven by genome instability.

More recently, he has been in the spotlight for his work with NAD+ precursors and their role in aging and has been helping to develop therapies that replace NAD+, which is lost with aging, in order to delay the diseases of old age. Below are a selection of questions and answers from the AMA, and we urge you to head over to Reddit Futurology to check out the other questions that people asked.

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In addition, a small number of posters will be selected for oral presentation.


Poster topics should lie within the scope of the conference: Research contributing to the eventual postponement of age-related decline in health, with an emphasis on measures that repair damage rather than slowing its creation. Poster submissions are due on January 31, 2019.

To submit your poster go to:

https://www.undoing-aging.org/abstracts.html

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Many mutations accumulate in the esophagus as we age.


Scientists at the MRC Cancer Unit of the Wellcome Sanger Institute and other departments of the University of Cambridge discovered that healthy esophageal tissue accumulates very high numbers of mutations with age, to the point that, by the time middle age is reached, it is likely to contain more cells with a particular mutation than cells without it [1].

Abstract

The extent to which cells in normal tissues accumulate mutations throughout life is poorly understood. Some mutant cells expand into clones that can be detected by genome sequencing. We mapped mutant clones in normal esophageal epithelium from nine donors (age range, 20 to 75 years). Somatic mutations accumulated with age and were caused mainly by intrinsic mutational processes. We found strong positive selection of clones carrying mutations in 14 cancer genes, with tens to hundreds of clones per square centimeter. In middle-aged and elderly donors, clones with cancer-associated mutations covered much of the epithelium, with NOTCH1 and TP53 mutations affecting 12 to 80% and 2 to 37% of cells, respectively. Unexpectedly, the prevalence of NOTCH1 mutations in normal esophagus was several times higher than in esophageal cancers. These findings have implications for our understanding of cancer and aging.

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Judith Campisi as a speaker for the 2019 Undoing Aging Conference.


At Lawrence Berkeley National Laboratory and at the Buck Institute for Research on Aging, Dr. Judith Campisi established a broad program to understand the relationship between aging and age-related disease.

Judith Campisi says: “Aging research has entered an era of unprecedented hope for interventions that can prevent, delay and, in some cases, reverse much of the functional decline that is a hallmark of aging. There is still a lot of research to be done! I am delighted to be among the speakers at Undoing Aging 2019, where I will discuss the opportunities and challenges of our recent research.”

“Judy has been a towering figure in the field of senescent cells for decades; among other things she pioneered the idea that senescent cells could be actively toxic to their environment and the discovery that cell senescence has a beneficial physiological role in wound healing. She was also one of the first senior gerontologists to appreciate the merits of the SENS approach when I first proposed it in 2000, and her support for it and us ever since has been of incalculable benefit in helping it achieve the mainstream status it enjoys today.” says Aubrey de Grey.

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To paraphrase Churchill’s words following the Second Battle of El Alamein: Google’s announcement about their new venture to extend human life, Calico, is not the end, nor even the beginning of the end, but it is, perhaps, the end of the beginning.

(MORE: Google vs. Death)

Since the dawn of civilization, humanity has been enslaved by the knowledge that no lifestyle choice, no medicine, no quirk of fate can enable anyone to live for more than a few decades without suffering progressive, inexorable decline in physical and mental function, leading inevitably to death. So soul-destroying has this knowledge been, for almost everyone, that we have constructed our entire society and world view around ways to put it out of our minds, mostly by convincing ourselves that the tragedy of aging is actually a good thing. And why not? After all, why be preoccupied about something one cannot affect?

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Today we are delighted to announce there is to be a third fund match for the NAD+ Mouse Project!


Today, we are delighted to announce that there is to be a third funding match for the NAD+ Mouse Project!

Dr. David Sinclair will be personally matching the next $5000 in donations for the last 10 days of the campaign to help reach the final $60,000 goal. Now, that is what we call a devoted scientist!

If the project can reach this final fundraising goal, the project will greatly increase in scope and become a full-on lifespan study, including the collection of months of long-term data for NMN. This is the ultimate goal of the project and will allow the research team at Harvard Medical School to obtain enough NMN to be able to investigate a wide range of health measures as well as get a detailed picture of how long-term treatment with NMN affects the aging processes.

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