Humans battle a number of biological processes with age that lead to the gradual deterioration of cells and tissues. Frailty, disability, disease, and death are all costly fates of aging. Researchers who study aging aim to change this fate, however, the mechanisms of aging are still all but fully understood.
In 2013, López-Otín and colleagues attempted to identify these biological processes and proposed the original nine hallmarks of aging: genomic instability, telomere attrition, epigenetic alterations, mitochondrial dysfunction, loss of proteostasis, deregulated nutrient-sensing, cellular senescence, stem cell exhaustion, and altered intercellular communication. These hallmarks of aging have helped to provide a framework for thought about the causes and consequences of aging, as well as potential targets for therapeutic interventions. Now, nine years later, the hallmarks of aging have been updated in light of recent discoveries.
“In the nearly past 10 years, our in-depth exploration on ageing research has enabled us to formulate new hallmarks of ageing which are compromised autophagy, microbiome disturbance, altered mechanical properties, splicing dysregulation, and inflammation, among other emerging ones.”
Among the keynote speakers who presented at this symposium was Vilhelm A. Bohr, M.D., Ph.D., Chief of the Laboratory of Molecular Gerontology at The National Institute on Aging and a distinguished member of the Aging Editorial Board. Dr. Bohr presented new data on the DNA damage response enzyme poly ADP-ribose polymerase 1 (PARP1)-related pathways. He suggested that PARP1 might be present and functional in mitochondria. Dr. Bohr also presented on the short-term use of NAD+ supplementation in age-related hearing loss.
“Here, Professor Bohr’s group showed that the treatment of mice with NR [nicotinamide riboside] was capable of restoring NAD+ in the cochlea of aged mice to the levels found in young mice. Even more strikingly, NR treatment limited the progression of hearing loss in ageing mice while stopping the progression of hearing loss in old mice.”
The Meeting Report
The authors’ review summarized all the work presented in this symposium, consisting of some of the latest findings in the field and contextualized by the updated hallmarks of aging. Their summaries of presentations were grouped by theme, including theories of aging and cellular senescence, new insights into telomeres and cellular senescence, inflammation, NAD+ and aging, mitochondrial dysfunction, premature aging and DNA repair, and cardiovascular, cerebrovascular and muscular pathologies of aging.
“The presented data showcased novel research at the forefront of the field, with a focus on a possible increase in healthspan and the amelioration of age-related diseases. Here, both the possible clearance or delay of senescent cells as well as possible interventions in the NAD+ system were discussed. While both of these approaches are promising, they are not without limitations.”
A panel discussion took place at the end of the symposium which was moderated by Eric Verdin, M.D., President and CEO of the Buck Institute for Research on Aging and also a distinguished member of the Aging Editorial Board. In sum, the symposium hosted several established researchers and young scientists who presented and discussed the latest findings in age-related research. They discussed new aging research in concert with how it connects to the old and new hallmarks of aging.
“Amalgamation of the ‘old’ and ‘new’ hallmarks of ageing may provide a more comprehensive explanation of ageing and age-related diseases, shedding light on interventional and therapeutic studies to achieve healthy, happy, and productive lives in the elderly.”
Conclusion
The goal of the “New Hallmarks of Ageing” symposium was to provide a platform for researchers to discuss the latest findings in aging research and to update the hallmarks of aging in light of new discoveries. While many promising discoveries have been made in the last decade, the authors cautioned that more work is needed to better understand aging and how these findings can be translated into therapies that improve human healthspan and quality of life. Discussions and research shared at this symposium have the potential to lead to new insights and breakthroughs in the field of aging research.
“At this point, tremendous progress has occurred, but a unified theory of ageing that can fully explain the process is still missing, and many open questions remain, both on a cellular and organismal level. Whether it is possible to target the ageing process at its core, or whether a combination of approaches is needed to target the aspects encompassing ageing, remains to be solved in the future.”
Click here to read the full review paper published by Aging.
Aging is an open-access journal that publishes research papers bi-monthly in all fields of aging research. These papers are available at no cost to readers on Aging-us.com. Open-access journals have the power to benefit humanity from the inside out by rapidly disseminating information that may be freely shared with researchers, colleagues, family, and friends around the world.
Following the Second Interventions in Aging Conference, meeting organizers Dr. Brian Kennedy and Dr. Linda Partridge discuss their overview of the meeting proceedings that was published by Aging in 2017, entitled, “2nd interventions in aging conference.”
Researchers explain their studies that were published in Aging
Behind the Study is a series of transcribed videos from researchers elaborating on their recent oncology-focused studies published by Aging. Visit the AgingYouTube channel for more insights from outstanding authors.
—
Dr. Brian Kennedy
I’m Brian Kennedy, I’m a professor at the Buck Institute for Research on Aging and a visiting professor at National University of Singapore.
Dr. Linda Partridge
And I’m Linda Partridge and I’m Director at the Max Planck Institute for Biology of Aging in Cologne, Germany. And also Director of the Institute for Healthy Aging at University College London.
So, Brian, how did you get into aging research?
Dr. Brian Kennedy
The funny thing was when I went to graduate school, I’d worked in yeast as an undergraduate, and I decided that I was not going to work in yeast anymore. But the more I realized about how difficult it was to work in mice, the more I wanted to work in yeast. And so there was another graduate student and I that wanted to go to Lenny Guarente‘s lab, and we decided to work in yeast and we wanted to figure out something completely crazy to do.
And we came up with two ideas: One was yeast apoptosis, which was a little weird for a single-celled organism and the other was aging. And we decided that aging was the least-
Dr. Linda Partridge
Mr. Nobel Prize.
Dr. Brian Kennedy
It’s true. We decided that aging was the least implausible of the two. And so we did that, but there’s a whole field on yeast apoptosis now too, so I guess we would have been okay. How about you?
Dr. Linda Partridge
Well, I got into it crabwise, really, because I started out life as an evolutionary biologist. So from the evolution point of view, it’s a completely weird trait because development produces a wonderfully functioning young organism and then it all goes to hell. You’d think it would be a lot easier to maintain it and to produce it in the first place. So I became very interested in how aging evolves and it is indeed really peculiar it’s almost certainly given what we’ve learned recently about the mechanisms of aging, actually bad effects in old age of genes that are good in the young. So I think that’s pretty interesting if you think about it as genes driving the old organism too hard to do the kinds of things that young organisms can do very well. I think it makes quite an easier process to think about, put it that way.
Dr. Brian Kennedy
And what we started the puzzle, both of us have worked on this a lot is, you know we’ve been trying to show that the pathways that are modulating aging are conserved. And it’s always kind of a puzzle that there’s so much conservation if this is a trait that evolution never really cared about that much. So it’s… I’ve never quite got that satisfied in my mind. What do you think about that?
Dr. Linda Partridge
I guess what I think is that the processes that you and other people have come up with, there are ones that do drive good things in young organisms. So the things that make for growth, for reproduction, for strong immune responses, for effective muscles and movement, all the things that young organisms have to do. But they seem to be set at too higher level when you get old, and I think that way it is actually quite easy to understand why it’s evolutionarily conserved because presumably the kinds of genes that control growth and reproduction evolve very early on.
Dr. Brian Kennedy
I agree. I actually argue with people that aging is going to be easier to modify than disease. So I think it’s going to be easier to keep people healthy than it is to wait until they get sick and try to treat them and make them better. I think of it as very simplistically as a state of homeostasis versus disequilibrium, you know, while you’re still relatively healthy, it’s fairly easy to tap into these pathways … relatively easy to tap into these pathways … and try to maintain that. But once you get into a state of disequilibrium, which I would call chronic disease of one sort or another, then you’ve got a problem. You’re kind of fighting entropy at that point and trying to put things back together again is very difficult.
Dr. Linda Partridge
Yes, it’s very interesting talking to colleagues in other areas about that idea because one gets a kind of ‘yuck’ response. So does that mean that humans are going to have to take pills when they’re healthy to prevent disease? You can point out that people do that already around statin and aspirin and things that lower high blood pressure. None of these are dealing with disease states, they’re in anticipation of possible disease states and trying to prevent them. So there’s plenty of taking pills to prevent things already, but for some reason, when you talk about it as a likely outcome of research into aging, there’s quite often a kickback, even from other scientists.
Dr. Brian Kennedy
I think most of the things we take, you know that are really working effectively really are aging drugs as much as they’re disease drugs. So you mentioned aspirin, but not just that I mean, look at statins, look at beta- blockers, look at early diabetes drugs like Metformin. All of them are targeting early risk factors for chronic disease, and I kind of feel like these risk factors are right at the interface between aging and disease itself.
Dr. Linda Partridge
They’re right on the nexus of the way in which aging acts as a risk factor for disease, and I think the other thing about them is that it’s quite clear that they’re turning out to have off-licence effects. Most of these drugs have a much broader therapeutic range than they’re generally used for. Which is exactly what you’d expect if they’re in there in that nexus between aging and disease.
Dr. Brian Kennedy
So what’s exciting to you now in your research? Where are you going in the next five years?
Dr. Linda Partridge
Well, funnily enough, I’m very much into drugs. So we’ve been doing quite a lot of drug work with drosophila and based exactly on this idea that mechanisms of aging are conserved. We’re starting to take a number of these drugs into mice, but also starting to do some big database stuff with humans, looking at particular pathways that have come up in the model organisms and asking whether SNPs associated with those pathways in humans ones that are either likely to increase the activity of the pathways concerned or decrease it or associated with particular types of disease risk.
So one can do this process called Mendelian randomization, which in theory gets rid of a lot of the effects of genetic background and focuses on a particular SNP. Now I think there’s enough data coming in on humans that we can really start to do the population genetics on these pathways, and I’m terribly excited by that.
What about you?
Dr. Brian Kennedy
Well, I have two goals right now. One is to try to go back to the simple organisms and really take a systems approach and try to take a yeast cell for example, and be able to describe all the features of aging, not just one gene at a time. And so we’re working a lot in sort of systems biology approaches there, but I think the main goal I have is-
Dr. Linda Partridge
Do you mean you’re looking at gene combinations or how are you doing it?
Dr. Brian Kennedy
Yes. Gene combinations, but also working with collaborators to look at how signaling pathways change with age to start to really understand longitudinal processes in a yeast cell. So the idea is to combine that with the genetic data and try to put the puzzle together.
Dr. Linda Partridge
I think that’s interesting.
Dr. Brian Kennedy
My main goal really is to get human and to start testing interventions in humans because I think we have enough knowledge now that we have things that are likely to work and we have reasonable candidate biomarkers, none of which are completely validated, but I feel good about some of them. And if you put that together, I kind of see it as a lock and key fit. You know we’ve got a bunch of interventions which are potential keys, and we’ve got a bunch of biomarkers which are potential locks, and we have to figure out which keys fit in which locks. So I’m looking at strategies to really test that in humans, either through academic research or through private companies.
Dr. Linda Partridge
So do you think companies are going to be interested in doing the kind of research that would target more than one disease, or do you think the way in is going to be to go for particular disease states? How do you think we should do it, operationally?
Dr. Brian Kennedy
I’d much rather target healthy aging or health span or prevention of multiple diseases. And I think there are companies that are thinking about that now, but they’re still relatively small generally. I think PhRMA kind of walks up to that ledge and looks over and then backs up. But eventually I think that it’s going to happen. I think what we need is some evidence that we can really modulates aging pathways. And that’s where this biomarker strategy or the kinds of things that [inaudible] is doing to get multiple disease parameters simultaneously in clinical trials. Those kinds of things, I think, are you just need a couple of success stories and then people start to get it. So I’m agnostic as to whether it’s done academically or privately, I just want to make it happen and so you know.
Dr. Linda Partridge
So what do you think about… We know so much from the animal studies about rapamycin now we probably know more about that than any other drug in the context of aging. Do you think there are going to be more clinical trials with rapamycin for off-license applications? Do you think it would be a trial for Alzheimer’s for instance?
Dr. Brian Kennedy
You know, there’ve been a lot of talk about trials for Alzheimer’s and I don’t think one has gotten started yet. But I think you’re going to start to see more and more of this. Then of course, there’s a lot of research to try to figure out how to either dose rapamycin or everolimus, which is the first generation of that rapalog in a way that doesn’t have the toxicity or to develop new drugs that have the efficacy without the toxicity. So I think both of those approaches are moving forward.
Novartis just spun off a small company to try to do this, and so I think that there’s renewed interest in trying to inhibit mTOR, but there’s still a lot of open questions about how it’s going to be best to do that. But having said that the number of potential indications, I mean, not to mention aging itself is so large that there’s clearly value into doing this successfully. So I’m pretty excited about where that’s going to go. I think that’s only one of a bunch of pathways though and you’re looking for new drugs and new pathways, and I think we’re going to find that there are a lot of different potential entry points for intervention in aging as we go forward.
Dr. Linda Partridge
I think it’s a time of great excitement. I just hope that some of the human trials get done while I’m still active. I’d love to see some successes with people.
Dr. Brian Kennedy
But you will be active for at least 20 more years, so …
Dr. Linda Partridge
Lots longer if somebody comes up with a pill.
Dr. Brian Kennedy
You know, that’s why I think doing this Fusion Conference has been so fun. You know, we’ve done two of these now in Cancun, and the idea is to bring different groups of people to look at different strategies for interventions in aging. I think that the conferences are relatively small, but we try to recruit a wide range of people. So we get people discussing different kinds of ideas that don’t normally talk. That’s what I think the strength of it is what do you think?
Dr. Linda Partridge
I agree with that. I really like the format of those conferences because they have a low upper limit on the number of delegates deliberately. So that most people can give talks or posters and there’s plenty of time for discussion. And what I noticed at those meetings correspondingly is that the discussion is very intense. Almost everybody talks to everybody else at some point during the meeting. So there’s real interchange of ideas as you say, between people who we deliberately invite from different areas, and I think it’s been a great success and it’s also been very nice to see it going more and more translational. There is more and more interest in mechanisms that are going to give rise to preventative measures rather than just the basic research, which has been fantastic and was necessary to get anywhere. But people really are trying to push it into helping people now. And I find that very exciting. So yes, I think meetings are great.
Dr. Brian Kennedy
Yes, I know, and I think as we go forward with these meetings, we’ll probably continue to try to emphasize these human intervention studies as much as possible.
Dr. Linda Partridge
I think that’s very much a specialty of that meeting.
Dr. Brian Kennedy
Because there are other meetings that really focus on the basic biology of aging, but this is really trying to get at the next step.
Dr. Linda Partridge
Yeah. Yeah. It’s particularly good when we can get basic scientists and clinicians together, I think. And also people from the various companies who might do something about the discoveries. I think it’s a very good mix of people that way.
Dr. Brian Kennedy
I can’t, you know, in my better moments, I think that we’re almost right at a tipping point where we’re going to push over this wall and then all of a sudden everybody’s going to be saying, oh, targeting aging is common sense in 10 years. I still have the bad moments where I feel like the little soldier walking into the wall and never go anywhere too.
Dr. Linda Partridge
Yes. I fluctuate between those two points as well, but I find myself feeling optimistic more and more often seeing what’s happening.
Dr. Brian Kennedy
That’s good. Well, it’ll be exciting to see where the field goes moving forward…
Dr. Linda Partridge
Yeah, indeed. Indeed.
Click here to read the full meeting report, published by Aging.
Aging is an open-access journal that publishes research papers monthly in all fields of aging research and other topics. These papers are available to read at no cost to readers on Aging-us.com. Open-access journals offer information that has the potential to benefit our societies from the inside out and may be shared with friends, neighbors, colleagues, and other researchers, far and wide.
Impact Journals is an exhibitor/sponsor and will be presenting its scientific integrity process at the Society for Scholarly Publishing (SSP) Annual Meeting, occurring virtually from May 24-27, 2021.
Listen to an audio version of this announcement
BUFFALO, NY-May 19, 2021 – Scientific integrity is a crucial component of scholarly publishing. In order to consistently publish high-quality science, it is integral to have strong ethical standards for scientific and academic integrity. At Impact Journals, a growing industry of digital technologies, tools, and ideas are constantly being added to our robust scientific integrity process. Impact Journals (based out of Buffalo, New York) is an international open-access publisher of journals in the field of biomedical sciences.
The Impact Journals process to maintain scientific integrity in scientific publishing is built around several components: 1.) Publicly available ethics statements; 2.) Adherence to industry standards for scientific publishing; 3.) Diligent and insightful peer-review; 4.) Elimination of plagiarism; 5.) Image forensics service; and finally, 6.) If a problem arises post-publication, we conduct investigations following COPE guidelines in cooperation with the authors and their affiliated institution.
In addition to our diligent peer-review process, Impact Journals uses advanced image forensics service to check applicable images in all submitted papers. This service includes multiple in-house and third party tools for image screening as well as to compare newly submitted images against images found on the Internet and those that have already been published in one of our journals. You may find more details about our scientific integrity process at Oncotarget.com, under Editorial Policies.
To learn more about Impact Journals, or any of our journals, please visit www.impactjournals.com.
About Impact Journals:
Impact Journals is an open-access publisher, focusing on topics surrounding cancer research, all fields of aging research, and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Our mission is to provide scientists with the opportunity to share their exceptional discoveries, offer services that enable rapid dissemination of results, and to present vital findings from the many fields of biomedical science. Our goal is life without disease.
Impact Journals Impact Journals LLC 6666 E.Quaker St. Ste. 1 Orchard Park, NY 14127
As the world continues to account for COVID-19, this year the American Association for Cancer Research (AACR) Annual Meeting will be a virtual event. Aging, by Impact Journals, is proud to be a participant in the conference on April 10-15 and May 17-21, 2021.
Listen to an audio version of this article
BUFFALO, NY-MARCH 25, 2021 – Aging is indexed by PubMed/Medline abbreviated as “Aging (Albany NY)”, PubMed Central, ISI/Web of Science: Science Citation Index Expanded (abbreviated as Aging‑US and listed in the Cell Biology category; since June 2017 it has also been listed in the Geriatrics & Gerontology category), and Scopus /Rank Q1 (abbreviated as Aging).
Every year, the American Association for Cancer Research (AACR) organizes a conference program that covers the latest discoveries in cancer research. Topics include population science and prevention, cancer biology, translational and clinical studies, survivorship, and advocacy. This conference aims to highlight work from the best minds in research and medicine from institutions all over the world. The journal Aging,byImpact Journals, will be participating at the AACR Annual Meeting this year.
Impact Journals is an open-access publisher of rigorously peer-reviewed scientific literature, and owns four medical research journals, including Aging. Aging was launched by Impact Journals in 2009 with the goal of spotlighting high-impact papers, authored by scientists who study the process of aging and age-related diseases—including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome.
Aging has published outstanding papers and reviews by highly-cited authors and award winners, including Andrew V. Schally (Nobel Laureate), Shinya Yamanaka (Nobel Laureate), Lawrence Donehower, Toren Finkel, Stephen Helfand, Gerald Shadel, Andre Nussenzweig, Maurice Burg, Karen Vousden, Leonard Guarente, and Dale Bredesen. Importantly, the Aging Editorial Board also comprises numerous prestigious award winners, including Nobel Laureate Elizabeth H. Blackburn, and many other distinguished scientists, including Cynthia Kenyon, Judith Campisi, Leonard Guarente, Michael Hall, Mikhail Blagosklonny, Vera Gorbunova, David Sinclair, Jan Vijg, and Thomas Rando.
The journalhasrecently concluded its 12th year of publishing and has become Impact Journals’ featured journal. Learn more about Aging and Impact Journals at the virtual 2021 AACR conference on April 10-15 and May 17-21, 2021. Registration will be open through the beginning of the event.
About Aging:
To learn more about Aging, its publication standards, and past or current issues, visit www.aging-us.com.
Impact Journals is an open-access publisher with four scientific journals: Aging, Oncotarget, Genes & Cancer, and Oncoscience. Our mission to provide scientists with the opportunity to share their exceptional discoveries, offer services that enable rapid dissemination of results, and to present vital findings from the many fields of biomedical science. Our goal is life without disease.
Impact Journals LLC, 6666 E.Quaker St. Ste. 1, Orchard Park, NY 14127
