Mois : décembre 2024

I first met Dr. Mehmood Khan in 2022 at the inaugural Longevity Summit Dublin, where organizers Aubrey de Grey and Martin O’Dea made a bold decision to include policy and advocacy discussions alongside the traditional focus on longevity research. Like many others in the audience, I was captivated by the forceful, engaging, and compelling one-man show that Khan delivered with apparent ease. “This is how public persuasion is done,” I remember thinking. “We need more people like him on our side.”

Khan had already enjoyed an illustrious career before joining the longevity movement, holding high-profile roles such as Vice Chairman and Chief Scientific Officer of Global Research and Development at PepsiCo and President of Global R&D at Takeda Pharmaceuticals. However, Khan is not just a high-profile bureaucrat. He has a solid background in science and healthcare, having served as Chief of the Endocrine Division at Hennepin County Medical Center in Minnesota and later as a faculty member in endocrinology at the Mayo Clinic and Medical School.

It’s this rare combination of qualifications and interests that led him to his current role as CEO of Hevolution, the world’s best-funded healthspan-focused non-profit, created by, no less, a royal Saudi decree. Despite being a relatively new player in the field, Hevolution has swiftly established itself as a dominant force, leveraging its overflowing war chest both boldly and strategically.

Hevolution is the largest sponsor of the $100-million-plus XPRIZE Healthspan and supports dozens of researchers in the fundamental biology of aging across the globe. It has also begun investing in longevity startups. With so much happening, an interview with Mehmood Khan was long overdue. We sat down to discuss Hevolution’s vision, its progress, and his thoughts on the future of the field.

Let’s start with your personal journey to the longevity field. I know it’s an unusual one.

Unlike most experts, I haven’t been in the field long directly. Indirectly, it’s been my whole career. I was an endocrinologist, practiced at the Mayo Clinic and the University of Minnesota, saw a lot of patients with diabetes, metabolic disease, obesity. Much of my early research, if you go back 25 years or so, was around metabolic disease and obesity, and this was before aging was itself considered a discipline.

My career has progressed from being focused in a specific subject area to being fascinated by how you can impact health at a large scale, which is what bridged my interest from medicine to food. I had a faculty appointment in food science as well as in medicine because I trained in food science at the College of Food Science and Agriculture. This was 35 years ago, and that progressed to thinking about global challenges, whether it’s food supply, water, or the carbon footprint of large industries like PepsiCo.

The chance to converge all of this together crystallized with the whole field of healthspan. When I started looking at this field, everyone was still primarily talking about longevity. And it was clear to me that longevity is not the target here – healthspan is. What we’ve spent the last years doing, and it’s been my privilege to lead the team, is to focus Hevolution much more on healthspan than longevity.

This distinction between healthspan and longevity seems important to you. Yes, we have seen increases in longevity but not in healthspan in recent decades, which isn’t good, but do we really have to uncouple these terms to such an extent?

I think sometimes you have to uncouple it because it’s the vocabulary that you use that gets the traction with policymakers. I’ve spoken to a lot of health ministers, finance ministers, and several heads of state over the last few years. If we make this purely about getting people to live longer, it becomes interpreted as more dependency – more people to take care of, bigger pension bills, bigger health bills for Medicare, National Health Service in the UK, Japan, China, wherever you go.

If you talk about longevity, you end up with not a lot of interest at the very senior policymaker level. Health ministers, yes, but they’re not the ones holding the purse strings. You’ve got to convince the finance ministers, the labor ministers, the economy ministers that this is of national interest. It isn’t about people living longer for the sake of living longer, but about productivity.

If you talk to individuals (and we’ve surveyed them), and you ask, “Do you want to live longer?” – that won’t be their number one priority. But if you ask, “Do you want to live healthy as long as possible?” – yes, almost unanimously. So, as scientists, we may not uncouple it, but the average person on the street understands those two things differently.

More importantly, policymakers view these as two different things. I think it’s important for us as leaders in the field to say that our primary goal is to keep populations healthy as long as possible. The secondary benefit of that might be that people live longer. But if we start with the argument that we want people to live longer, that’s not going very far. It hasn’t gone for decades.

If you focus on life extension, you inevitably get sucked into debates such as “Is this against God (if you’re religious) or nature?” You get into all other kinds of ethical debates. But the minute you say, “I want people to live healthy for as long as possible,” there’s no disagreement about that.

Yes, that makes a lot of sense. Let’s now talk about Hevolution, which emerged in the field just a couple of years ago and has since become a major player.

Hevolution was created by a royal order from the King. It is chaired by His Royal Highness, Prince Muhammad, the Crown Prince and Prime Minister. It was the vision to take on a global challenge that would benefit as many people on the planet as possible. Healthy aging touches every human being. It’s a global challenge that affects every country, including the kingdom, so it’s very relevant locally across the Gulf, but globally as well.

It was set up as a nonprofit because the primary driver was to fund the science to move the field forward, accelerate the science into the marketplace with patient capital willing to take risks, and put it under a nonprofit umbrella. So, the incentives are aligned – we want our venture capital arm to succeed, attract other investors, and grow the size of the pie.

One part of that mission statement was particularly important to us: to extend healthy lifespan for the benefit of all. That’s something that is uniquely possible under the umbrella of a nonprofit. We want to democratize everything we do. We put that lens on everything we evaluate. Whatever we do, we look at it through the scalability lens. We’re not interested in technologies that might touch a few privileged people in the world, even though that may be where it starts. We look at it and ask ourselves, “How does this scale? Is there a path?”

Naturally, we care about another important issue: the bioethics of healthspan extension. It’s not just asking the question “Can it be done?” but also “Should it be done?”, and that shouldn’t be left just to the scientists. I am a scientist, and I should not be the one leading that conversation. I’m a strong believer that this should be something that experts in ethics are engaging with from day one.

Before we funded a single science grant, we put together a global ethics team, and that, to my knowledge, is the first time global bioethicists have been convened around the field of aging and asked to guide us and hold us accountable. Arthur Caplan, who is at the helm, is a world expert on ethics. He’s the chair of bioethics at NYU, previously Johns Hopkins, New Orleans. Julian Savulescu, founding chair of bioethics at Oxford, is another example.

This is a very interesting aspect of Hevolution I admit I’ve never heard of. I think many aging researchers don’t really want bioethicists around – they see them mostly as a nuisance. Can you name some of the insights this team has come up with?

There are a couple of things that they’ve started to push us to think about. One is, “How do you make this inclusive?” Not only the output, but the research. Initially, like everybody else, we were looking at the world and saying, let’s fund North America, the UK, but usually absent at the research table are people from the African subcontinent, South America, Latin America. Our bioethicists asked us why.

If you’re really going to address global aging, you have to understand aging in the context of the world. The continent that’s going to have the most elderly people in the world in the next 50 years is Africa, and yet, you almost never see people from Africa at aging meetings. It was a good push. We went to the WHO to explore possible collaborations: they’ve got a much better footprint there than we do. How do we collaborate with them? I don’t have an answer yet, but we’re working on it.

Another example is how we think about aging as a process in terms of when we would intervene versus not intervene. When is the earliest you should intervene? If you ask biologists, they’ll tell you that aging as a process starts around 14 days after conception. Should you intervene in an embryo? Should you intervene in a child?

I had the privilege of giving a couple of lectures at Yale Law School three or four years ago on the distinction between law and ethics in business. Something you learn when you look at this as a scientist (the lawyers already know that) is that the law is only a memorialization of a society’s ethics. Then, isn’t it our job as scientists to help convene that ethics discussion and move it forward alongside the scientific field rather than have it follow?

What’s your philosophy in choosing projects?

First, we want to fund the underlying science in the biology of aging. That’s our primary target. We don’t want to just fund another research study on Alzheimer’s, diabetes, dementia, osteoporosis. There’s lots of research going on and lots that’s been done. Most of it has come from working backwards from the end case. They say, now you’ve got osteoporosis, what can I do to increase your bone mineral density? If you have dementia, what can I do to slow it down? Not what can I do to prevent it.

So, understanding the biology is the key. The second thing is understanding how and when to intervene. When you start asking those questions, one thing that will surface is that we still don’t really know how to measure aging as a biological process. Yes, there’s DNA methylation, there’s this and that. Every six months you’ll hear of a new biomarker, then another, but most of them come from relatively small studies correlated with one or two variables. We have A-glycohemoglobin (HbA1c) for diabetes, but not its equivalent for aging. We know what cardiovascular risk profiling looks like based on biomarkers – LDL, HDL – but we don’t have the same for aging.

So, one bucket is how do you measure aging? This has to be predictive and correlate with treatment. Ideally, a good biomarker will reverse with treatment. This is why we funded the global meeting on biomarkers of aging at Cold Spring Harbor earlier this year. We brought together the world’s experts, both clinicians and biomarker experts and regulators, to start a series of discussions.

I strongly believe that we should fund this research and facilitate this debate. For instance, we should think about how we make biomarkers of aging open source. You know, if LDL cholesterol had been patented, we probably wouldn’t have statins.

Right now, we’ve got about 150 labs and 200 principal investigators around the world that are funded by us. We’re also funding partnerships where we’re a partner in the scientific grants. Basically, just like the NIH, we say, send us your best idea. We then send it to independent review; we don’t like to review the grants ourselves. I don’t need to take phone calls saying, “Hey, Mehmood, I just submitted this grant. What do you think?” I wouldn’t even know what you’re talking about because it goes to an independent panel.

I’ll give you an example. We’re interested in proteostasis at the cellular and tissue level. How do we bring the best minds together? In this case, we went to Richard Morimoto at Northwestern, one of the world’s academic leaders in proteostasis, and said, if you would put your dream team together and develop a series of research plans around that, we’ll fund you. And he did. It’s almost 30 million dollars. That’s an example of a partnership where we targeted the area, found the world expert, and asked that PI to put together a multi-center team.

The value of that is he’s going to collaborate with people who might have been competing with him for grants in the past. Now he can say, “Listen, we can get funding together if we come together.” That’s the catalyst role that we play as Hevolution. We’re catalyzing the field by catalyzing collaboration.

Another way you’ve been catalyzing the field is through XPRIZE Healthspan, where Hevolution is the lead and single-largest funder. Can you tell me more about this collaboration? In particular, since you talked about biomarkers, what do you think about their idea of reversal of age-related loss of function as the endpoint?

It’s very exciting to see how they’re incentivizing the world. They’ve done this successfully in other fields, putting the best minds, ideas, and resources to answer the question. This is the moonshot, this is the challenge: show us 10 years of reversal (of loss of function). Let’s go!

Evidence shows that in prizing mechanisms such as XPRIZE, the multiplier is about 8 to 10. For every dollar of the prize money, the collective investment brought in by the competitors is eight to ten times that. For a chance to win 80 million I’m going to put in two million, three million from grants or investors. This scenario repeats itself a hundred times over, everybody’s competing, and finally, the 80-million prize draws 800 million into that field.

That’s the beauty of this model. The reason we support it is that, in the back of my mind, a hundred-million-dollar prize means a billion dollars will potentially be mobilized. That’s the leverage. Every team that’s competing is going to either find investors, or government funding, or donors.

Regarding the specific biomarkers, when we went to the table, I said that nobody from Hevolution or any sponsor should be involved in defining the endpoints or sit on the judging committee. We helped find independent judges, we helped put together the endpoint committee to come up with the definition, but that was the limit of our involvement.

I was delighted when Professor Patrick Maxwell accepted. He’s the Dean of the Medical School at the University of Cambridge – a world-class researcher. Ironically, some of the people we approached turned us down for a very interesting reason. When they learned about the details of the prize, they said they couldn’t do it because they now wanted to compete. We still counted that as a win.

Tell me about the upcoming second Hevolution Summit. What is special about this particular longevity conference?

Actually, we did a small regional one early in 2023 in partnership with the National Academy of Medicine, and that one was focused on the Gulf area. So, it’s our third event of this type but the second Healthspan Summit.

At the first Healthspan Summit, we brought a lot of people together – it was bigger than anybody expected. We had people with subject matter expertise and people who were there because they were curious. The delightful part is we had people travel from all over the world, and we didn’t pay anybody to speak – no honorarium. We said, if you want to come and speak, it’s a privilege, and we’ve held that bar.

People loved the fact that we convened experts from different disciplines. We had regulators talking with investors, talking with scientists. People also appreciated the depth of the discussion on all the topics.

For the second summit, we’re taking the best of what we did and making it better. Now we have a chance to tell the world what we’ve accomplished since the first one. We can showcase research programs we’ve funded, partnerships – not ourselves, but we get the experts, the funded scientists to stand up and talk about their field.

We’ve now announced three companies we’ve invested in. We can showcase not only what those investments are but why we’ve invested in them. By then we may have announced more as well. We look to bring investors and these startups even closer together for matchmaking.

We’ll have updates from the XPRIZE – by then, we’ll be able to show the world how many teams there are, where they’re located, what types of fields they’re involved in, what science they’re interested in. The second summit is about the proof points.

The challenge I have right now is focus. Think about what I just shared with you: 2000 grants reviewed, 200 PIs funded, three companies announced, potentially five partnerships. I can’t put everybody on stage. It’s a good problem to have, but I think the world wants to hear from these people. They don’t want to hear from me.

The last piece, which I think will be the most exciting in the future, is matchmaking between our ecosystem of scientists. One thing we can do better than any government funding agency is cross borders. We can fund teams across borders much more easily than the NIH or the MRC because their priorities lie first and foremost within their own borders. We’re trying to cross these borders.

I have heard you on several occasions talking about the need to work across the entire ecosystem, including with public opinion and decision makers. However, I understand that Hevolution hasn’t funded any projects in that particular field. Why is that?

We’re very careful. We see ourselves as advocating for the field, convening different experts, but we’re not a lobby. We can’t legally lobby, nor do we want to.

However, we’ve had several policymakers, ministers, former ministers, attending our meetings – in the UK, in the US, in the Middle East. We’ve had very senior people from industry: Jon Symonds, Chairman of GlaxoSmithKline, was there as an example. Numerous CEOs from big pharma, small pharma, all engaging.

This means we have a chance to bring these parties together and hope that will shape the discourse around policy. We’re seeing early signs of that traction. Recently, I had a meeting right here in Riyadh with a former health minister. He was on a formal visit, but he asked his staff to arrange a private lunch meeting with me. That tells us that people like him are looking to Hevolution as a credible source, they are interested.

I was delighted to hear that when ARPA-H was announced by President Biden, one of the pillars this year was going to be aging. That’s a huge win for the field. Nobody’s going to be able to put in the sort of resources that the U.S. federal government can: the NIH’s budget is 44-plus billion dollars. Put 10 percent of that toward aging, and you’ve made a massive impact on the field’s progress.

How optimistic are you about the near future of our field?

I’m quite optimistic for several reasons. One, it’s a public health imperative. Two, it’s an economic imperative. Three, the science is now optimistically telling us that something can be done about it. You can have the first two, but if nothing can be done about it, so what?

The fourth reason is your field – the media. Today, I see three bodies in the media. One is mostly about the throw-away terms, the sound bites, those are people who don’t do their homework. Whatever the latest vitamin cure is, they’ll push it. That hurts our field. The second is the outlets that not only understand the science but find a way to communicate it to the readers who might not have a scientific background. The third is core science – the fact that Nature now has Nature Aging is huge. One of the top two journals in the world having a whole series on aging tells you something.

What then frustrates you? What bottlenecks do you see that you’d love to change in terms of public opinion, regulation, the scientific environment?

I see two major things. One is that sometimes, people in this field get over-enthusiastic and ahead of their own data. While I love passion and energy, the challenge is the risk to credibility. If you suddenly start making statements like, “In my lifetime, you’re going to live to be 150,” it sets an expectation and that hurts the field. Let’s not get ahead of ourselves. That frustrates me. Let’s stick with the evidence. Let the data push this field forward.

The old African proverb we often quote is “If you want to go fast, go alone. If you want to go far, take everybody with you.” Sometimes people in our field forget this wisdom. This is going to take a village. It’s a team sport. It’s going to take multiple players in different scientific and non-scientific disciplines. We’ve got to bring them together.

Just trying to create likes on social media in the short term gets a lot of publicity, sometimes gets you stardom, but that’s usually short-lived. Sometimes in that process, one forgets that it’s about the field, not oneself. I’ve been a CEO for a long time. I’ve been running large organizations and small organizations. One of the things you learn as a senior executive, whether at organizations as big as PepsiCo or as small as a biotech company, is that it’s always about the field, the business, the enterprise, not oneself. And if you remember that, you can move mountains.

Reseachers publishing in Antioxidants have combined three antioxidant and anti-inflammatory compounds and tested their effects in human beings.

Three complementing choices

The first component the researchers included was AM3, a compound that is core to the Inmunoferon supplement and is an immunomodulator that has been found in trials to aid against infections [1]. Some prior work has found that AM3 also assists against immunosenescence [2]. However, as these researchers note, little work has been done in that area, and that work did not establish whether or not it could do anything to curtail age-related immune dysfunction.

The second component was spermidine, a polyamine that has been reported to improve the cellular maintenance process known as autophagy, thereby also ameliorating immunosenescence [3]. Spermidine has also been reported to assist in gut function by returning macrophage polarization to a less inflammatory state [4].

The third component was hesperidin, a flavonoid that recent prior work had found to have potential effects against multiple diseases, including hepatitis [5] and several metabolism-related disorders, such as diabetes [6], obesity [7], and non-alcoholic fatty liver disease [8]. The researchers hold that these effects most likely originate from its effects against inflammation, such as its suppression of the senescence-related protein MMP-9 [9], and on immune response [10].

All three of these ingredients are sold in various parts of the world as supplements and are generally considered nontoxic. No side effects were noted in this study.

Effects on inflammation, oxidation, and immune function

A total of 35 healthy people aged between 30 and 60 years old completed this study, which lasted for two months. The doses of these three compounds are distinctly different: 150 milligrams of an AM3-containing compound and 50 milligrams of hesperidin were included alongside only .6 of a milligram of spermidine.

As their primary target, the researchers utilized ImmunolAge, an immune system-based metric that calculates such factors as neutrophil activity and natural killer activity [11], as their measurement of biological age. They noted that the participants in both the placebo and treatment groups had, on average, an ImmunolAge of 20 years over chronological age, which the researchers ascribed to the stress and anxiety that the participants were reporting at baseline.

The placebo effect was not statistically significant, while ImmunolAge was significantly decreased in the supplement group by approximately 10 years. While this finding is strongly positive, the researchers also note that this was still higher by a decade than the participants’ chronological ages.

This difference in ImmunolAge was due to stronger responsiveness of both neutrophils and lymphocytes along with an increase in phagocytosis, the ability of immune cells to engulf and consume pathogens. In general, the cells were more responsive to perceived threats and more willing to attack them. Despite these benefits to other immune cell types, natural killer cells were unaffected.

This increase in immune responsiveness was accompanied by significant decreases in circulating inflammation. The well-known inflammatory factors TNF-α and IL-1β were significantly decreased, while the anti-inflammatory factor IL-10 was increased. However, the inflammatory factor IL-6 was also increased.

Oxidative stress was also significantly affected by this supplement combination. The natural antioxidant glutathione was found to be more active, while the amount of used, oxidized glutathione in the blood was decreased.

Moreover, the researchers hold that this supplement combination has significant effects on oxi-inflammaging, a combination of oxidative stress and inflammaging that has been suggested to have significant effects on lifespan [12].

More research needed

While this was a randomized, controlled trial with significant positive results, it was a pilot trial of only 35 people, not a Phase 2 or larger Phase 3 trial. This trial solely used an immune system-based calculation as a proxy for biological age; no epigenetic clock was used, and other lifespan-related biomarkers were not obtained. Cellular senescence, which the researchers had mentioned and was likely to be affected by the circulating biomarkers studied here, was also not directly analyzed. This study was conducted on a middle-aged group; it is unclear whether or not older people would have responded in the same way.

The researchers also noted that such factors as diet were not altered, with participants encouraged to continue their usual eating habits, and it was unclear how many natural antioxidants the participants were already consuming. Additionally, it is infeasible to determine if such a supplement combination can actually extend lifespan in healthy people through direct analysis, and the researchers recommend animal studies in further work.

Literature

[1] JA, G. M., & Schamann, F. (1992). Immunologic clinical evaluation of a biological response modifier, AM3, in the treatment of childhood infectious respiratory pathology. Allergologia et Immunopathologia, 20(1), 35-39.

[2] Villarrubia, V. G., Koch, M., & MC, C. C., González, S. and Alvarez-Mon, M.(1997) The immunosenescent phenotype in mice and humans can be defined by alterations in the natural immunity reversal by immunomodulation with oral AM3. Immunopharmacology and Immunotoxicology, 19, 53-74.

[3] Zhang, H., & Simon, A. K. (2020). Polyamines reverse immune senescence via the translational control of autophagy. Autophagy, 16(1), 181-182.

[4] Niechcial, A., Schwarzfischer, M., Wawrzyniak, M., Atrott, K., Laimbacher, A., Morsy, Y., … & Spalinger, M. R. (2023). Spermidine ameliorates colitis via induction of anti-inflammatory macrophages and prevention of intestinal dysbiosis. Journal of Crohn’s and Colitis, 17(9), 1489-1503.

[5] Li, S., Hao, L., Hu, X., & Li, L. (2023). A systematic study on the treatment of hepatitis B-related hepatocellular carcinoma with drugs based on bioinformatics and key target reverse network pharmacology and experimental verification. Infectious Agents and Cancer, 18(1), 41.

[6] Mirzaei, A., Mirzaei, A., Khalilabad, S. N., Askari, V. R., & Rahimi, V. B. (2023). Promising influences of hesperidin and hesperetin against diabetes and its complications: a systematic review of molecular, cellular, and metabolic effects. EXCLI journal, 22, 1235.

[7] Xiong, H., Wang, J., Ran, Q., Lou, G., Peng, C., Gan, Q., … & Huang, Q. (2019). Hesperidin: A therapeutic agent for obesity. Drug design, development and therapy, 3855-3866.

[8] Morshedzadeh, N., Ramezani Ahmadi, A., Behrouz, V., & Mir, E. (2023). A narrative review on the role of hesperidin on metabolic parameters, liver enzymes, and inflammatory markers in nonalcoholic fatty liver disease. Food Science & Nutrition, 11(12), 7523-7533.

[9] Lee, H. J., Im, A. R., Kim, S. M., Kang, H. S., Lee, J. D., & Chae, S. (2018). The flavonoid hesperidin exerts anti-photoaging effect by downregulating matrix metalloproteinase (MMP)-9 expression via mitogen activated protein kinase (MAPK)-dependent signaling pathways. BMC complementary and alternative medicine, 18, 1-9.

[10] Camps-Bossacoma, M., Franch, À., Pérez-Cano, F. J., & Castell, M. (2017). Influence of hesperidin on the systemic and intestinal rat immune response. Nutrients, 9(6), 580.

[11] Martínez de Toda, I., Vida, C., Díaz-Del Cerro, E., & De la Fuente, M. (2021). The immunity clock. The Journals of Gerontology: Series A, 76(11), 1939-1945.

[12] Miquel, J. (2009). An update of the oxidation-inflammation theory of aging: the involvement of the immune system in oxi-inflamm-aging. Current pharmaceutical design, 15(26), 3003-3026.

While the United States has just celebrated a holiday that opposes caloric restriction, researchers there and around the world continue to discover the effects of it and other interventions against aging. Let’s see what’s been done in November.

Interviews

Rozalyn Anderson Explains Caloric Restriction: At the University of Wisconsin-Madison, Dr. Rozalyn Anderson is studying one of the oldest-known and yet most powerful anti-aging interventions: caloric restriction (CR).

Advocacy and Analysis

AI in Longevity: The Reality Today: Back in 2006, a website called “The Death Clock” appeared on the internet, with a promise to answer one of life’s greatest questions: “When will I die?” Just like the fascination with death dates drove internet traffic to that particular site in the 90s, so too does the interest in a healthier, longer lifespan drive longevity investment in 2024.

The Best Talks of GSA 2024: We bring you a selection of presentations from the annual conference organized by the Gerontological Society of America.

Research Roundup

Towards Fine-Tuned Control of Gene Expression: In a groundbreaking Nature paper, researchers have developed synthetic regulatory sequences that could prevent targeted gene therapies from having effects in unwanted cell types.

Ketogenic Diet Effective Against Multiple Sclerosis in Mice: Scientists have found that both a ketogenic diet and oral supplementation with ketone bodies alleviate symptoms of multiple sclerosis, a serious autoimmune disorder, in a mouse model.

Mesenchymal Stem Cells Rejuvenate Aged Mice: In a new study, the researchers administered human umbilical cord-derived mesenchymal stem cells to aged mice and observed reduced degeneration in multiple organs, changes to microbial composition, metabolic alterations, improvements in behavior and ability, and reduced fearfulness.

Extracellular Vesicles for Treating Arthritis: A study in Pharmacological Research has found that small extracellular vesicles derived from embryonic stem cells alleviate osteoarthritis in cells and mice.

Rejuvenating the Hippocampus With Metabolites: Researchers have reported in Aging Cell that injecting specific one-carbon metabolites into the hippocampus can rejuvenate its cells.

A Senolytic Accelerates Reproductive Aging in Aged Mice: In a new study, researchers tested the impact of the senolytic drug ABT-263 on the reproductive systems of old female mice. ABT-263 treatment did not rescue age-related changes in hormonal levels, further depleted ovarian reserves, and didn’t improve most of the tested signs of reproductive aging.

Preventing Alzheimer’s Proteins From Accumulating: Boosting a key autophagy-related protein discourages a core component of Alzheimer’s from taking hold, according to a study published in Aging Cell.

Study of Direct Reprogramming Challenges Consensus: Scientists have shown that in a direct cellular reprogramming scenario, neurons are produced almost exclusively by a rare subtype of multipotent cells. Their findings, they claim, change our understanding of reprogramming, but not everyone agrees.

Engineering T Cells to Fight Brain Cancer: Researchers publishing in Nature have reported a new advance in developing chimeric antigen receptor (CAR) T cells to fight solid tumors in the brain.

Intranasal Spray Alleviates Early Alzheimer’s in Mice: A novel therapy based on induced neuronal stem cells shows promise in a mouse model of Alzheimer’s disease – and it can be administered intranasally.

Dietary Diversity Is Associated With Delayed Aging: An analysis of data from over twenty thousand people has indicated that greater dietary diversity is associated with slower biological aging.

How Exercise Preserves Function in Motor Nerves: In Aging Cell, researchers have described the specific cell types that give exercise protective effects against motor nerve degeneration.

Finding Cells That Send Signals Against Arthritis: In Aging, researchers have reported that deriving extracellular vesicles from mesenchymal stromal cells (MSCs) in fat tissue has beneficial effects in models of osteoarthritis.

Building an Atlas of Human Ovarian Aging: The researchers of a Nature Aging paper used multi-omics approaches to investigate cellular, molecular, and genetic drivers of human ovarian aging.

Time-restricted eating reveals a “younger” immune system and reshapes the intestinal microbiome in human: Overall, TRE showed multiple anti-aging effects, which may help humans maintain a healthy lifestyle to stay “young”.

Association of dietary anthocyanidins intake with all-cause mortality and cardiovascular diseases mortality in USA adults: This research indicates that an appropriate dietary intake of anthocyanins is associated with a reduction in overall mortality rates

Acute exercise boosts NAD+ metabolism of human peripheral blood mononuclear cells: These results demonstrate that acute exercise triggers NAD+ biosynthesis of human PBMCs with potential implications for immunometabolism, immune effector function, and immunological exercise adaptions.

High-intensity interval exercise is more efficient than medium intensity exercise at inducing neurogenesis: These findings suggest that HIIT enhances neurogenesis more robustly than MIIT in both niches, with HCA1 playing a crucial role in V-SVZ neurogenesis.

Pterostilbene Targets Hallmarks of Aging in the Gene Expression Landscape in Blood of Healthy Rats: The findings provide a rationale for pre-clinical and clinical longevity studies and encourage investigations on PTS in maintaining cellular homeostasis, decelerating the process of aging, and improving conditions with chronic inflammation.

Effect of nicotinamide riboside on airway inflammation in COPD: a randomized, placebo-controlled trial: In exploratory analyses, treatment with NR showed indications of upregulated gene pathways related to genomic integrity in the airways and reduced epigenetic aging, possibly through a reduction in cellular senescence.

Investigating the efficacy of ergothioneine to delay cognitive decline in mild cognitively impaired subjects: These results add to existing data that ergothioneine is safe for extended consumption and may hold the potential to delay cognitive decline in elderly adults.

Sex Differences in Response to Diet Enriched with Glutathione Precursors in the Aging Heart: This work supports the concept that aged male and female hearts are phenotypically different. These basic differences may affect the response to pharmacological and diet interventions, including antioxidants.

The Administration of Resveratrol and Vitamin C Reduces Oxidative Stress in Postmenopausal Women: Vitamin C increased the total antioxidant capacity of postmenopausal women with insulin resistance by up to 33%. However, using resveratrol and/or vitamin C alone or in combination did not present significant differences in insulin resistance.

Human Supplementation with AM3, Spermidine, and Hesperidin Enhances Immune Function, Decreases Biological Age, and Improves Oxidative-Inflammatory State: The researchers propose that this supplement may be a strategy to rejuvenate biological age and achieve healthy aging.

Metabolite signatures of chronological age, aging, survival, and longevity: These results characterize many metabolites involved in aging and point to nutrition as a source of intervention for healthy aging therapeutics.

A small-molecule screen identifies novel aging modulators by targeting 5-HT/DA signaling pathway: This study offers a way for the discovery of drugs that promote healthy aging, and provides potential interventions for preventing behavioral deterioration in the elderly.

Mendelian randomization analyses support causal relationships between gut microbiome and longevity: These microbial taxa and pathways may potentially play a protective role in promoting longevity or have a suppressive effect on lifespan.

Gut microbiota and epigenetic age acceleration: a bi-directional Mendelian randomization study: This study implicates the potential causal effects of specific microbiota on EAA, potentially providing novel insights into the prevention aging through specific gut microbiota.

Slowed epigenetic aging in Olympic champions compared to non-champions: The data suggest that rigorous and long-term exercise from adolescence to adulthood has beneficial effects on epigenetic aging.

Attitudes towards geroprotection: measuring willingness, from lifestyle changes to drug use: Future research may want to delve deeper into the role of facilitating trust relations between medical institutions and the public in promoting the use of geroprotective drugs.

Negative effects of lifespan extending intervention on resilience in mice: None of the three age-sensitive assays responded to the health-extending interventions in the way the researchers expected, and for some assays, including anesthesia response, interventions actually worsened outcomes.

Stem cell transplantation extends the reproductive life span of naturally aging cynomolgus monkeys: These findings demonstrate the beneficial effects of M-cell transplantation on aging ovaries and expand the understanding of the molecular mechanisms underlying ovarian aging and stem cell-based alleviation of this process.

Restoration of hair follicle inductive properties by depletion of senescent cells:  These data revealed that senolytic treatment of cultured human dermal papilla cells markedly increased their inductive potency in hair follicle regeneration.

News Nuggets

New Crowdfunding Project Looks for a “Better Rapamycin”: Ora Biomedical and the Rapamycin Longevity Lab have launched a project to screen more than 600 mTOR inhibitors in the hope of finding some that are superior to geroscience’s poster child, rapamycin.

Coming Up

The Longevity Summit Announces Fourth Annual Event: The Longevity Summit, a leading conference bringing together the complete ecosystem of longevity science and biotechnology, will hold its fourth annual event on December 3-4, 2024, at the Buck Institute for Research on Aging in Novato, California.