Dr. Aubrey de Grey is a biomedical gerontologist based in Silicon Valley, California, USA, and is the founder, President and Chief Science Officer of LEV Foundation, a biomedical research and advocacy charity focused on repairing the molecular and cellular damage of aging. He received his BA in computer science and Ph.D. in biology from the University of Cambridge. His research interests encompass the characterisation of all the types of damage that constitute mammalian aging and the design of interventions to repair and/or obviate that damage. Dr. de Grey is a Fellow of both the Gerontological Society of America and the American Aging Association, and sits on the editorial and scientific advisory boards of numerous journals and organisations. He is a highly sought-after speaker who gives frequent invited talks at scientific conferences, universities, companies in areas ranging from pharma to life insurance, and to the public.
Scott Douglas Jacobsen: So, you were started with the LEV Foundation. What is the LEV Foundation? It’s a new project.
Aubrey de Grey: Yes. LEV Foundation is a new nonprofit based in California. As you know, I’ve spent the past 20 years leading nonprofits. This is the third one. The main thing distinguishing LEV Foundation from my previous projects is that its flagship research work involves embarking on the last stage of development of the SENS portfolio.
So, of course, SENS, as I defined it 20-odd years ago, is a divide-and-conquer strategy that says, “Here are the various types of molecular and cellular damage the body does to itself throughout life.” Lots and lots and lots of them, but they can be classified into a manageable number of categories. The key point about that classification is that it maps 1 to 1 well, 1 to many with the various ways to repair damage. This is not precisely or adequately present in the more recent restatements of this concept, such as the hallmarks of aging over the past decade.
But it’s very important to have this mapping to have these generic approaches to repairing the damage that corresponds to the various damage categories. At the Research Foundation, and indeed before that at the Foundation, I was focused on the individual categories and the individual damage repair strategies, particularly the most difficult ones, because those were not being worked on by others who had different incentive structures and were constrained more by short-termism in one way or another. That’s gone well, although there’s still plenty to do.
However, the easier ones among the categories, particularly the ones that were easy enough that I wasn’t even working on at my previous organizations, have now been taken up by others to the point where they work in mice. One can see genuine benefits when applying these interventions in middle age to mice that have already accumulated some relevant damage. Of course, if you remove a type of damage, there may be a knock-on effect on the rate of other damage types. This may result in a modest increase in health span and lifespan, which has been reported in various cases.
So, coming back to what LEV Foundation does, we are leveraging that. We are taking those techniques and applying them to the same mice simultaneously, starting in middle age, using mice that are not genetically impaired or models of accelerated aging. This is something that nobody else is doing. There are a few experiments combining orally available drugs, which are valuable, but we firmly believe that to defeat aging properly. You cannot eliminate gene therapies, cell therapies, and such, which are not orally available and must be injected.
So yes, we are doing something unique. Our first attempt started about 18 months ago with mice already 18 months old. These mice normally live for about two and a half years; a few might make it to three years if you’re lucky. That’s exactly what has happened to our control group. However, the mice who were getting all four interventions we combined were doing quite well. A third of the subjects are still alive, so we consider this experiment successful. It’s a significant success in males because we genuinely see additive effects. In females, it is not very pleasant. All the benefits we’re seeing come from one intervention, namely rapamycin, which isn’t even a damage repair intervention, but the other three are. In males, there’s no question that the other three interventions provide additional benefits over and above rapamycin. We are very happy about that, and this strongly justifies and motivates us to conduct similar experiments in the future with other interventions and the same interventions at different doses.
The difficulty, of course, is that the experiments are relatively inexpensive. This particular experiment, which we are nearing the end of, cost three and a half million dollars. There are ways we can pare that down without compromising the information gained all that much, but it will still be in that order of magnitude. So, I’m doing what I do: spending my time on stage, on camera, and the phone, trying to get people to write checks. We are hoping to kick off the next study quite soon. After all, people care about their longevity.
Jacobsen: They tend to fear the process of dying more than death itself. With your extensive experience and connections in longevity research, what would you recommend for individuals to practice, especially those in middle-income households, to benefit from rational and enlightened self-interest? I recall you mentioning “listen to your body” in prior interviews. Beyond that, what would you suggest?
de Grey: First and foremost, listening to your body remains my main advice because people differ significantly. The subtle details of individual metabolisms vary from person to person and are crucial for optimization. Beyond general advice like not smoking, avoiding serious overweight, and maintaining a reasonably varied diet, it’s essential to find what works for you.
People often compare me with Ray Kurzweil in this context, noting that I don’t take any supplements while Ray takes 200 a day. The difference lies in our circumstances. Ray drew a lot of short straws, with a family history of cardiovascular disease and type 2 diabetes in his thirties. The difference between us is not in our thinking but in the problems we’re addressing.
I also emphasize that focusing solely on oneself could be better. Why are you concerned only about yourself? It is fashionable to care about your kids and parents. Even without considering that, people of different ages have varying probabilities of benefiting from the work people like me do. Regardless of age, there shouldn’t be any complacency or fatalism because the timeline of breakthroughs is unpredictable. People in 1900 thought powered flight was impossible, only to be proven wrong three years later. Conversely, Leonardo da Vinci’s designs for powered flight took 400 years to be realized. It can go either way, and we don’t know.
We will reach longevity escape velocity within 12 to 15 years, which means the second half of the 2030s. If we do, most people over 50 will be able to benefit, which is pretty good. But I always stress that there’s at least a 10% chance that we won’t get there for 100 years because we may hit unforeseen obstacles. So, you will benefit yourself probabilistically, no matter how old or healthy you are.
And the final thing I want to say is that the most important thing to avoid is stupid early deaths. When people ask me what I do, apart from saying I don’t take supplements, I say I don’t accept seminar invitations to dangerous countries. I wear a seatbelt even in the back seat. Things like that are quite important, too. Over and above all, the thing to do is contribute to the mission, one way or another, to the crusade, thereby hastening the arrival of the defeat of aging.
And whether that means writing me a check, interviewing me, advocating among your family, friends, and colleagues, or lobbying Congress, it could mean anything. I’m delighted that a wide and diverse community is doing all those things now. I often think back to 20 years ago when there was just me. I’m very proud of the contribution I’ve made to building that community, quite apart from the contribution I’ve made to science.
Jacobsen: What is the Alliance for Longevity Initiatives?
de Grey: The Alliance for Longevity Initiatives is one of the organizations I have seed-funded recently. It was well spent because they are a 501(c)4, which, for those who don’t know, is a bit different from a 501(c)3, which is what the LEV Foundation is. A (c)3 is a charity where you get tax advantages for donating, but it is restricted in what it can do. In particular, it is not allowed to lobby elected representatives.
Conversely, with (c)4s, you don’t get the tax benefit, or at least it works differently, but they are allowed to lobby, and that’s what the Alliance for Longevity Initiatives does. It has masterminded many things over the past few years and has more to come. One thing it did was set up a congressional caucus of a dozen congresspeople who care about aging and are in a position to influence legislation. An even more important thing they’ve done now is at the state level. They worked with the state senator in Montana to draft and push through legislation that expands the Right to Try Act.
The Right to Try Act was passed at the federal level several years ago, and it says that if you are terminally ill and you have exhausted all the options for approved treatments for whatever is wrong with you, then you are allowed to access things that are not yet approved as a last resort. Fine. But most of us would prefer not to be terminally ill in the first place. So what happened in Montana was they passed something that said that as long as the treatment in question has passed phase 1 of clinical trials, it got through the safety side but not anything to do with efficacy yet, not the expensive phases 2 and 3, you can access it in Montana however healthy you are.
You do not have to be ill. This is significant. Numerous drugs have passed Phase 1 trials but have yet to progress further. Phases 2 and 3 are still in progress or have been abandoned due to a lack of funding. Regardless, this is immensely important.
Moreover, the race is on to replicate that legislation in other states and possibly at the federal level. There was a recent setback. The senator in Montana who initiated this ran in the Republican primary for federal Congress and did not win. Consequently, he will not be able to pursue it at the federal level, but he can continue his efforts in Montana and set an example for other states. I am hopeful that this initiative will continue.
Jacobsen: What is the Healthspan Action Coalition?
de Grey: This is another organization that we have more than seed-funded. The Healthspan Action Coalition is a sister organization to the LEV Foundation. As its name implies, it focuses on building coalitions.
I build communities of crusaders, activists, and like-minded individuals. The Healthspan Action Coalition focuses on being much more diplomatic and politically correct and bringing together a broad array of people with diverse interests under the understanding that nearly all diseases and disabilities, even those with early onset in childhood, have aspects in common with aging. Research on aging, therefore, benefits everyone. The coalition aims to have an increasingly louder voice in the corridors of power, akin to the A4LI, but in a very different manner.
Two exceptional individuals lead it. Bernie Siegel, who 20 years ago became a prominent spokesperson for the regenerative medicine community, organized the World Stem Cell Summit for most of those years, a conference that has been a powerhouse of networking and community building. The other leader is Melissa King, who served as the executive director of the California Institute for Regenerative Medicine (CIRM) for the first eight years. Both are titans in this field and are now laser-focused on aging. The HSAC is doing an enormously important job that will become increasingly influential over the years.
These individuals must have extensive experience in being diplomatic and politically savvy, areas that take work to come to me. My strengths lie in being more outspoken, which has advantages and disadvantages.
Jacobsen: When discussing transplantation on demand, a concept advocated by the LEV Foundation, what are some potential pathways for this to become a reality? Once the technology is mastered, what are the different ways it can be implemented or requested?
de Grey: We should probably discuss this aspect further on our website. This particular area of interest is connected to one organization we have seed-funded, Kain Ice. Kain Ice is essentially a reboot of a previous company, Aragost, run by the same individual. The technology this company is pursuing is related to cryopreservation. As many people know, I have been a strong proponent of cryonics for a long time, the idea of preserving individuals at very low temperatures shortly after they have been declared legally dead in the hope that we may be able to revive them in the future. However, it has long been recognized that this technology would have enormous value in organ transplants, as currently; many people die on waiting lists because there is no available organ that is sufficiently compatible with their immune system.
The primary issue is that organs decay rapidly, necessitating immediate transplantation from donor to recipient. This urgency means that organs can only be transported over long distances with significant degradation. The goal is to extend, ideally indefinitely, the period during which an organ remains viable by storing it in liquid nitrogen. Simplistic methods of cryopreservation, however, cause substantial damage to the organ beyond any preexisting damage. This problem also applies to cryonics.
Thus, this research area aims to discover methods for cryopreserving organs or individuals with minimal damage. A significant breakthrough occurred about 30 years ago when Greg Fahy and his colleagues at 21st Century Medicine developed a technique called vitrification. Vitrification involves an intricate mixture of cryoprotectants that allows an organ to solidify without forming ice crystals, substantially reducing damage. However, this method does not eliminate damage, as cryoprotectants are somewhat toxic, and large-scale fracturing or cracking can still occur in the organs, which is detrimental to their function upon warming.
Kain Ice is focused on an innovative technology called insufflation. This technique involves pumping cold gas through the vascular system to cool the organs more rapidly, effectively addressing toxicity and fracturing issues. The gas used in this process is helium. The aim is to preserve organs to minimize damage, enabling them to be stored and transported as needed for transplantation.
Jacobsen: Regarding the original seven pathways of aging and disease involving damage to genetics, cells, and gross anatomy, which do you believe have made the most progress and still require significant research to achieve practical application?
de Grey: First, it is not a matter of one over the other. There has been substantial progress, but much work remains. Starting with stem cell research, this field addresses cell loss. A significant development in recent years is partial reprogramming in vivo, eliminating the need to transplant new stem cells outside the body. Instead, it enhances the resident cells’ stem-like properties, restoring regenerative capacity. This is crucial. Additionally, we have made enormous strides in manipulating stem cells in the laboratory before transplantation, perfecting stem cell therapies.
One example of notable progress is in treating Parkinson’s disease, a condition caused by the loss of dopaminergic neurons in the brain. This research advances significantly, providing a promising outlook for addressing aging associated with cell loss.
The method to address this issue, specifically replacing those cells with stem cells, was demonstrated to be effective around 30 years ago, though only sporadically, as the necessary techniques to generate the correct type of cells needed to be better understood at the time. Success was, therefore, rare but remarkable when it occurred. With our advanced understanding of stem cell manipulation, efforts are being renewed. Three or four clinical trials are underway, and considerable optimism exists. Although there is still work to be done, progress is promising.
Turning to cancer, in the early days, I proposed a strategy to control cancer by inhibiting telomere elongation. This was undoubtedly the most ambitious and challenging of my proposed approaches. Many people agreed that while the rest of SENS made sense, this particular approach seemed unfeasible. I understood the skepticism and recognized the need for improvement. Enter Jerry Shay, an outstanding Dallas scientist and a leading telomere research figure. He identified a drug that kills cells attempting to elongate their telomeres rather than merely stopping telomeres from elongating. This drug essentially disrupts the telomere in conjunction with telomerase, effectively turning telomerase into a suicide gene. This drug is now in phase 2 clinical trials, and I am very hopeful about its potential. I refer to it as WILT 2.0, a more straightforward realization of my original concept.
I could continue, but the point is clear: there is progress in every area. I highlight the advancement in partial reprogramming and stem cell research. This trend is seen across all categories. Each of the seven categories now has multiple alternative approaches addressing them.
Jacobsen: What other organizations do you think do important frontline work in regenerative medicine?
de Grey: There are many now. Let’s consider the private sector for a moment. One person to whom I owe an enormous debt of gratitude for his contributions to my work over the past several years is Michael Greve from Germany. He amassed considerable wealth during the early days of the Internet in Germany and, around 2016-2017, began making substantial investments in aging research. Much of this investment took the form of donations to the SENS Research Foundation, which significantly enhanced our capabilities.
While he no longer donates due to the current economic climate, I hold no blame because he has redirected his funds into investments in start-up companies. These start-ups are among the most critical in the field. I say this not only because many of them are spin-offs from the SENS Research Foundation but also because he employs the same criteria I use to select projects: he focuses on areas grossly neglected by the rest of the world.
Among these companies are Revel Pharmaceuticals, Cyclarity, and Elastin, which are undertaking vital work and are essentially unique in their fields. This is fantastic. Additionally, extensive work is being conducted in academia, although most are tangential to the damage repair philosophy and paradigm.
It would help if you had tangential work as well. I’m happy with the increasing diversity that’s appearing out there.
Jacobsen: There is mythos around regenerative medicine, the idea being hopeful and skeptical, even satirical to others. What about one day you take a pill, which does a lot of the core work in repairing damage and reversing or stalling aging? Is there anything on the horizon, like a single fix, that you could take orally, for instance?
de Grey: Not a single fix. But, of course, we have to define precisely what we mean by single here. I often give examples of MMR, the measles, mumps, and rubella vaccine. Of course, it’s not a single vaccine; it’s all three vaccines that you happen to get in one injection. Similarly, you can certainly imagine a scenario in which one would have an injection of 300 things at the same time. From the recipient’s point of view, it would be a single thing, but only from that point of view.
Certainly, we can say that, by and large, things that we supply that have a large effect on aging will need to be injected rather than delivered orally simply because you can’t do gene therapies and cell therapies orally. But injections aren’t so costly. The one thing that might have a big effect and that might even be supplied orally is a good senolytic. At this point, we have several, and this is another example of an alternative approach that, back 20-odd years ago, I had never even conceived. I knew that senescent cells were accumulating and needed to be removed, but I assumed that we would have to do it with some suicide gene therapy, some approach that would directly attack the gene expression differences in senescent cells. I never considered that one might be able to find small molecules that would selectively kill such cells.
But we have those now. We don’t need those who are as selective as they are and to bear the most selective approach for cutting off senescent cells. The most powerful one involves the immune system and enhances it to better identify and eliminate cells through natural immune clearance. However, the point is that senescent cells have diverse consequences for the body. When Judy Campisi first considered the possibility that senescent cells might be actively toxic rather than merely inactive, it was around the same time that I was considering the idea that cells full of mutant mitochondria might be actively toxic. She and I had interesting conversations back then about this, and her focus back then was restricted to cancer. She was saying, well, some of the things these cells are secreting will be bad for neighbouring cells that may already be precancerous. The senescent cell itself is protected from further uncontrolled cell division, but the ones next door might not be, and so this might be oncogenic.
That was the thinking at that time. However, as time passed, we discovered that the SASP, or senescence-associated secretory phenotype, can have many diverse and negative effects that may contribute to various aspects of aging. Our current experiments show that it could be doing better, but that’s probably for technical reasons rather than because analytics are a bust in general. So, we need to work more on analytics.
It’s possible that orally available analytics can be improved in terms of efficacy. However, I suspect the approach will have a limit, and we will do better with the immune attack or optimization I mentioned. Yes, that’s an example.
Jacobsen: What project do you think is your most promising outside experiment on mice?
de Grey: Our project at the SENS Research Foundation, and of course the variations on that same theme we want to pursue, cost money, but it offers the best value for money in the field regarding the amount of information gained per dollar spent. It is inherent in the definition of any divide-and-conquer strategy, including for aging, that you have two phases. You develop the individual components, and then you put them together.
When you put them together, you find out what works, what combinations are synergistic, and which are antagonistic and cancel each other out. The absolute priority of the field ought to be conducting dozens of these large-scale experiments. We need 1,000 mice, maybe 4 or 5 different interventions combined in various subsets, and checking both healthspan and lifespan, as we are doing at the SENS Research Foundation. We perform a lot of different healthspan measures. So, yes, that’s what needs to be done.
Jacobsen: How can people get involved through time, skills, or expertise?
de Grey: There are many ways to get involved now, and that’s very important because not everyone, only some, is financially. Some people need to decide which areas of science to enter. Not everyone is Peter Thiel. This reminds me to mention one of the other organizations I started a few years ago, which I’m extremely proud of. It has gone from strength to strength.
It’s now called the Longevity Biotech Fellowship. Originally, it was called Less Death. Every few months, they run a retreat somewhere in the world, bringing together about 50 newcomers to the field and a dozen veteran mentors. The purpose is not only to educate but also to network and form partnerships and affiliations. It’s been wildly successful.
They’ve run five retreats so far, and they’ve had an unbelievable success rate in terms of impact on people’s careers. So, whenever anyone asks how they can help, I direct them to the Longevity Biotech Fellowship. It works.
Jacobsen: What do you consider the moment when you decided that aging was the field to dedicate your life to?
de Grey: Oh, I can pinpoint that. It wasn’t exactly a moment but a gradual realization over a year or two in the early nineties when I realized that my wife, a senior biologist nearly 20 years older than me, was not interested in aging. This was so bizarre that it took me a while to accept and believe it was true. But it wasn’t just her but all the other biologists I met through her.
But it had never crossed my mind that anybody could not think aging was the world’s most important problem and, of course, that it was a problem potentially solvable with medicine. Biologists are working on this. Yes, it’s a hard problem, so you don’t hear much about it, but I had yet to experiment with asking anybody about this. Gradually, I noticed that we should have talked about aging. I started asking questions, and after getting over the shock over a year or two, I concluded that I had to switch fields.
I have been working in artificial intelligence research for quite some time. I had convinced myself that I was good at working on hard problems, and I also knew that switching fields often worked well. People come in not encumbered by the conventional wisdom of their new field and look at a problem differently. So, I can contribute, and the rest is history.
Jacobsen: Aubrey, thank you very much again for your time today.
de Grey: It’s my pleasure. Thank you. Thanks for having me back. You’re welcome.
Jacobsen: Thanks so much.
De Grey: See you next time.
***
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[YAOUNDE] Nigeria is to begin the immediate rollout of 5,000 doses of mpox vaccines while the Democratic Republic of Congo (DRC) eyes its first shipment of 65,000 doses, as Africa steps up measures to control the multi-country outbreak.
The vaccine, administered in two doses, will go first to people at high-risk, including health workers and those living in areas with high infection rates, according to Nigeria’s National Primary Healthcare Development Agency.
Matshidiso Moeti, WHO regional director for Africa, said the delivery of 10,000 doses to Nigeria by USAID this week signified “a clear demonstration of international solidarity in the face of global public health emergencies”.
“The emergence of the new, more virulent variant (Clade Ib) and the increase in human-to-human transmission, with new routes such as sexual transmission, remains a cause for concern.”
Flaubert Mba, Centre for Research on Emerging and Re-Emerging Diseases
Nigeria became the first African country to receive the vaccine after confirming 40 cases of the disease, whose symptoms include fever, swollen lymph nodes and a rash leading to blisters.
The DRC, the country worst affected, is expecting to receive 65,000 doses of the vaccine on 1 September, announced Jean Kaseya, director-general of the African Centres for Disease Control and Prevention (Africa CDC), during an online press conference on Wednesday (28 August).
A health worker examines skin lesions that are characteristic of mpox on the back of a young child at the mpox treatment centre at the Nyiragongo General Referral Hospital, north of Goma in the DRC on 14 August 2024. Credit: Guerchom Ndebo / WHO
He said 50,000 doses would be sent by the US while 15,000 will be provided by Gavi, the Vaccine Alliance.
Kaseya said the JYNNEOS vaccine, made by Danish pharmaceutical company Bavarian Nordic, was one of the surest ways of stopping the mpox epidemic, alongside epidemiological surveillance and screening.
He stressed the vaccine was the same one used in the US and Europe to stem an outbreak of mpox – formerly known as monkeypox – in 2022.
“It has been given to millions of Americans and Europeans, which has made it possible to stop [that] epidemic,” he told the press conference.
Residents of Weta village in Maniema province, eastern DRC read information about how to avoid mpox, provided by health officials. Credit: Eugene Kabambi / WHO
In July, the emerging infectious diseases foundation CEPI announced trials in the DRC to see if vaccinating people already exposed to mpox stops them getting sick and spreading it.
Kaseya said Africa CDC would be sending 72 epidemiologists to affected areas in September to collect more data on case numbers, citing problems with the reliability of current data.
“These epidemiologists, in addition to the support they will be giving to the teams in the field, will also be focusing on the quality of the data, so that we can have data that will enable us to make good decisions,” he said.
“In the coming weeks, we will begin to provide what we believe to be quality data thanks to this support.”
Bushagara camp for displaced people in North Kivu, DRC. Identification of mpox cases in camps around Goma is concerning because the high population density can result in further spread. Credit: Guerchom Ndebo / WHO
Response plans
For the first time since its creation, Africa CDC declared on 13 August that the new mpox epidemic constituted a public health emergency of continental security (PHECS) in Africa. The next day, the WHO declared it a public health emergency of international concern (PHEIC).
Nicaise Ndembi, Kaseya’s scientific advisor and mpox response coordinator for the African Union and Africa CDC, told SciDev.Net: “This declaration marks an important moment in the history of public health in Africa and demonstrates the seriousness of the situation and the need for a unified, continent-wide response to this rapidly spreading disease.”
He stressed that it is now “urgent to take coordinated action at national, regional and international levels to stop the spread of mpox”.
Africa CDC is working to develop a “continental response plan”, which, according to Kaseya, should take into account the individual needs of each country. He said the plan will be presented to African heads of state for endorsement in the coming weeks.
The WHO has already launched a global strategic plan for mpox preparedness and response, which it says requires US$ 87.4 million over the next six months (September 2024-February 2025).
WHO director-general, Tedros Adhanom Ghebreyesus, speaking at the WHO Regional Committee for Africa in Brazzaville this week (26 August), stressed the need for more research and surveillance of the disease, as well as equitable access to vaccines.
WHO director-general Tedros Adhanom Ghebreyesus (centre) convenes the first meeting of the Emergency Committee to discuss the upsurge of mpox, on 14 August 2024. Credit: Lindsay Mackenzie / WHO
“I am certain that with the leadership of the affected countries and the support of the WHO, partners such as CDC Africa and others, we will be able to bring this epidemic under control quickly, as we have been able to do with other epidemics in recent years,” he said.
New variants
According to the latest WHO epidemiological data, 14 African countries have reported cases of mpox so far, with Gabon confirming its first case of the virus on 22 August.
The DRC remains the country hardest hit by the epidemic, with a total of 3,244 cases and 25 deaths recorded to date this year.
Burundi has recorded 231 cases, while a number of cases have also been confirmed in Central African Republic (45); Côte d’Ivoire (28); South Africa (24), and Congo (23).
There are two main types of the virus, Clade I and Clade II. Clade I, endemic to Central Africa, causes more severe illness and disease. The less severe Clade II strain caused the global outbreak in 2022 and is the type being seen in Nigeria.
People with #mpox may experience all or only a few symptoms. Mpox illness typically lasts 2-4 weeks. Source: CDC
However, a novel, sexually transmitted strain of the virus, identified as Clade Ib, has started spreading across the DRC and neighbouring countries, causing alarm.
Flaubert Mba, wildlife specialist and One Heath focal point at the Centre for Research on Emerging and Re-emerging Diseases, told SciDev.Net: “The emergence of the new, more virulent variant (Clade Ib) and the increase in human-to-human transmission, with new routes such as sexual transmission, remains a cause for concern.”
In addition to vaccination and the recommended hygiene measures, he believes that African countries need to focus on epidemiological surveillance, particularly in areas where wildlife and people interact.
“Mpox is a re-emergent zoonosis, meaning that it is transmitted from animals to humans and vice versa,” he explained.
“Particular emphasis needs to be placed on at-risk areas associated with risk mapping and areas where there have been outbreaks in the past.”
This piece was produced by SciDev.Net’s Sub-Saharan Africa French desk and edited for brevity and clarity.
September 10, 2024 was World Suicide Prevention Day. According to the World Health Organization,
“Every year 726,000 people take their own life and there are many more people who make suicide attempts.”
When I was five years old my mid-life father took an overdose of sleeping pills after he had become increasingly depressed because he couldn’t support his family doing the work he loved. Fortunately, he survived, but our lives were never the same. I grew up wondering what happened to my father, when it would happen to me, and what I could do to prevent it happening to other families.
Although females, as well as males, can die by suicide, males at every age are at higher risk than are females. Yet rarely is suicide discussed as a health issue for boys and men.
World Suicide Prevention Day (WSPD) was established in 2003 by the International Association for Suicide Prevention in conjunction with the World Health Organization (WHO). On September 10th each year they focus attention on the issues, reduce stigma and raise awareness among organizations, governments, and the public, giving a singular message that suicides are preventable.
The triennial theme for World Suicide Prevention Day for 2024-2026 is “Changing the Narrative on Suicide” with the call to action “Start the Conversation”. This theme aims to raise awareness about the importance of reducing stigma and encouraging open conversations to prevent suicides. Changing the narrative on suicide is about transforming how we perceive this complex issue and shifting from a culture of silence and stigma to one of openness, understanding, and support.
The call to action encourages everyone to start the conversation on suicide and suicide prevention. Every conversation, no matter how small, contributes to a supportive and understanding society. By initiating these vital conversations, we can break down barriers, raise awareness, and create better cultures of support.
I have been writing a series of articles—”Homecoming: An Evolutionary Approach for Healing Depression and Preventing Suicide.” In Part 1, I shared statistics from the National Institute of Mental Health, comparing the suicide rates for males and females at various ages:
Even during our youth where suicide rates are relatively low, males are still more likely to die by suicide than are females. It is also clear to me as my wife and I move into our 80s, that males and females face many challenges as we age, but it is older males who more often end their lives by suicide with rates 8 to 17 times higher rates than for females.
In Part 2, I discussed the evolutionary roots of male/female differences and quoted Dr. Roy Baumeister, one of the world’s leading social scientists. Understanding his work can better help us understand a lot about why men are the way they are and specifically why men are the risk-taking gender.
In his groundbreaking book, Is There Anything Good About Men? How Cultures Flourish By Exploiting Men, he says,
“If evolutionary theory is right about anything, it’s right about reproduction. Nature will most favor traits that lead to success at reproducing. But for thousands of years, men and women have faced vastly different odds and problems in reproducing. On this basic task, women faced good odds of success, whereas men were born to face looming failure.”
Men not only take greater risks than women, but also are less resilient and more prone to feelings of failure when they don’t feel they can offer something of value to those they love.
In Part 3, I show that suicide is the most prevalent form of violence and is the cause of more death than either war or homicide. We don’t often think of suicide as a form of violence or depression as an underlying cause of violence, but they are intimately related. The World Health Organization (WHO) produced an in-depth analysis of violence and published the information under the title, “The World Report on Violence and Health.” The report is the result of 3 years of work, during which WHO drew on the knowledge of more than 160 experts from more than 70 countries.
The report detailed estimated global-related deaths as follows:
These numbers vary in different years and rates of violent deaths also vary according by country and within each country with different groups. But clearly violence from suicide accounts for nearly as many deaths as war-related violence and homicides combined. All forms of violence are tragic and many have come to believe that violence is simply a part of human nature. But this is not true.
Violence of all kinds can be understood and prevented.
“Violence thrives in the absence of democracy, respect for human rights and good governance,”
said Nelson Mandela. We often talk about how a ‘culture of violence’ can take root. This is indeed true—as a South African who has lived through apartheid and is living through its aftermath, I have seen and experience it. No country, no city, no community is immune. But neither are we powerless against it.”
As we approach another presidential election in the United States, most everyone is aware of the threat to democracy we are facing and the conflicts that divide our country.
In Part 4, I offered guidance for all those who are ready to see the truth about the times in which we live and how we can live, love, and work, for good in the world.
For most of my professional life I believed that treating depression and preventing suicide involved helping individuals, couples, and families. A new perspective opened for me in 1993 at a men’s leadership conference in Indianapolis, Indiana. I’ve written a number of articles about my experience over the years, including my most recent, “Transformations: The End of the U.S. and the World as We Know It and The Truth About Our Collective Future.”
I said that an old kind of masculinity was on the way out. My colleague Riane Eisler describes two competing systems that humans have been engaging with that she calls the dominator system and the partnership system. Throughout the world emotionally wounded men who ascend to power have chosen a dominator approach to asserting power.
The old dominator systems were ruled by frightened men who came to believe that the only way to survive was to rule by force. Historian Ruth Ben-Ghiat describes these men in her book, Strongmen: Mussolini to the Present. She says,
“For ours is the age of authoritarian rulers: self-proclaimed saviors of the nation who evade accountability while robbing their people of truth, treasure, and the protections of democracy.”
Among the seventeen protagonists in her book she includes: Adolph Hitler, Saddam Hussein, Benito Mussolini, Vladamir Putin, and Donald J. Trump. Pulitzer-Prize winning journalist Anne Applebaum describes the way modern-day autocrats support each other in her book, Autocracy Inc.: The Dictators Who Want to Run the World.
“Nowadays, autocracies are underpinned by sophisticated networks composed across multiple regimes…The autocrats are rewriting the rules of world trade and governance as their propagandists pound home the same messages about the weakness of democracy and the evil of America.”
At MenAlive I have been supporting men and their families to embrace the partnership system and have recently created a way for organizations and individuals to belief in these ideas and practices to stay connected. You can learn more at our website, MoonshotforMankind.org and get news you can use on our substack, substack.com/@moonshotformankind.
If you’d like to read more articles on men’s mental, emotional, and relational health, you can subscribe for free at https://menalive.com/email-newsletter/.
Every suicide is a tragedy that affects families, communities and entire countries and has long-lasting effects on the people left behind.
Suicide does not just occur in high-income countries but is a global phenomenon in all regions of the world. In fact, close to three quarters (73%) of global suicides occurred in low- and middle-income countries in 2021.
Sticking to new habits isn’t easy, especially when they mean giving up old ones that make you feel good—at least temporarily—like binging talking dog videos or inhaling a burger on the way home from work. But there comes a time when making a change in the name of your health and happiness is more attractive than another night spent plastered to your couch. That’s where a program like the 75 Hard Challenge comes in. It’s not a weight-loss app, although followers do tend to shed some pounds. Instead, it’s a “mental toughness” protocol that helps instill new habits in fewer than three months. That’s not to say it’s without flaws.
This challenge is not easy to stick to. People often believe the more intense something is, the better the results. But this is a mistake if you aren’t careful. It’s important to learn about any new routine that overhauls your diet, exercise, and entire life and really evaluate if the pros and cons make it worthwhile. Learn all about 75 Hard, including 75 Hard Challenge rules and what you might stand to gain—or lose—if you try it.
What Is the 75 Hard Challenge?
The 75 Hard Challenge is primarily a mental toughness program with physical and behavioral habits created by entrepreneur and author Andy Frisella in 2019. In short, the challenge aims to build discipline and resilience—physically and mentally—by adopting a set of daily rules that you complete without fail for 75 days straight. Frisella sells a book about the challenge, but you can also learn about it from his podcast and all over the internet.
75 Hard rules dictate you drink one gallon of water daily and cut out alcohol and cheat meals including soda.
Jarren Vink
75 Hard Challenge Rules
There are five 75 Hard rules to follow during the 75 Hard Challenge. Here’s where it gets particularly tough: If you skip any of the items on the 75 Hard checklist on any given day, you need to start over from day one as a practice in forging mental toughness and self-control.
1. Follow a Diet
During the entire challenge, you should stick to a specific meal plan without cheat meals or alcohol. There’s no 75 Hard diet, per se. You get to choose. If you’re hoping to drop body fat, we recommend the best diets for weight loss. But if you’re just trying to adhere to a lifelong habit of healthy eating, stick to the best diets recommended by experts. Something like the Mediterranean Diet is more sustainable for life than, say, the keto or Paleo diet. Get more tips below.
2. Two Daily Workouts
Every day, you have to complete two 45-minute workouts with one being outdoors. Unfortunately, you can’t count activities like mowing the lawn, yard work, or leisure sports into the 75 Hard workout plan like golf, because they’re considered “daily chores” or “routines.” Typically, we don’t recommend two-a-days, especially if you’re not a professional athlete. To ensure you don’t overtrain, keep one akin to an active recovery, like steady-state cycling or yoga. If it starts to diminish your physical and mental well-being, stop.
3. Drink a Gallon of Water
Drink one gallon of water every day. This doesn’t include any other fluid intake, just clear H2O. Hydrating is obviously important. Drinking a gallon is likely unnecessary, but it won’t necessarily hurt you. If it helps up your intake, great.
4. Read Nonfiction
Part of the mental fortitude aspect of the challenge is reading 10 pages of a nonfiction book each day. Unfortunately, audiobooks don’t count, nor do magazines or sports pages. Sorry—there’s a reason this is called the hard 75 challenge.
5. Take a Daily Progress Picture
Take a photo of your body to track your progress each day. This could be a mirror selfie or one you loop your partner or roommate into taking for you. Just be sure to keep the lighting, location, time of day, and clothing items similar for each shot. For some, this is helpful over time to see incremental progress, however a daily log can be detrimental to others’ self-esteem if their body image isn’t positive.
Mediterranean Diet
Sam Kaplan
75 Hard Diet
Diet just might be the worst four-letter word in the English language. The good news is that you can choose your own diet structure for the 75 Hard Challenge.
Choose a Diet Plan
While you can pick your ideal diet, it has to be one that fosters positive physical change. Whether you’re losing fat, gaining muscle, building strength, boosting your intake of a specific micro or macronutrient (like protein), or improving overall diet quality for skin health, just pick something you think you can stick to for the entire 75 days without falling off the wagon.
Can you go 75 days without a hot slice of pizza or a burger? If you want to complete the 75 Hard Challenge, you’ll have to give up all of your normal cheat meals for the duration. That’s right—zero cheat meals (what would Dwayne “The Rock” Johnson say?). Instead, make some healthier swaps that are still tasty but easier on the waistline.
No Alcohol
There’s a strict no-booze rule for the 75 Hard Challenge, so plan accordingly. If you know you’ll be in a high-pressure social situation like a bachelor party or Super Bowl gathering, and you don’t have the willpower of steel, you might want to forego the plan until you know you can stick to it. Might we suggest nonalcoholic drinks like NA spirits, wine, and beer.
Running
Patrick Giardino/Getty Images
75 Hard Workout Plan
If you aren’t currently very physically active or have a difficult time sticking to a consistent routine, this may be a wallop: For the 75 Hard Challenge, you have to do two 45-minute workouts each day, and one of them has to be in the great outdoors. Luckily, the types of workouts you can do are pretty flexible so long as they are physically challenging and aren’t part of your regular daily routine. Here are some examples:
Cardio Workouts
Cardio should be part of your workout routine during 75 Hard, but you don’t have to go hell-for-leather every day. Many of the best cardio workouts can double up as your outdoor workout session.
Resistance training is a must for any serious training plan, so pick a style you enjoy or one you’re excited to try and stick to it for 75 days. Be sure to plan out your sessions in advance, increase the challenge as you go, and track your progress.
Bodyweight exercises (like pushups, pullups, and squats)
Powerlifting
Recovery and Flexibility Training
Including some low-key workouts into your routine is the ultimate overtraining prevention strategy. The less fit you are, the more of these sessions you should include—maybe four to five per week counting toward the 45-minute sessions. Scale down from there if you are more fit or as you progress throughout the challenge.
Yoga
Pilates
Mobility work
Walking
Stretching
High-Intensity Interval Training (HIIT)
If you plan to include HIIT training, do it sparingly. Too much high-intensity work will burn you out in no time. It’s not possible to do true HIIT training for a full 45 minutes, so if you’re going to add this modality to your routine, stick to 10 to 15 minutes at the end of a cardio session or after resistance training two to three times a week.
Pro tip: Skip high-intensity training altogether if your diet plan includes cutting calories. It’s a recipe for burnout.
Circuit training
Tabata workouts
Sprints
Battle Ropes
Justin Steele
75 Hard Pros
There’s a lot going for the 75 day Hard Challenge. Here are some of the main pros.
Builds Habits
We all know that consistency is king when it comes to results, and that’s the main tenant of 75 Hard: to build and maintain a consistent routine that includes five daily tasks every day without fail. Habits are automatic behaviors triggered by specific cues and learned through repetition, strengthening every time you complete the behavior—think brushing your teeth every night before bed or locking up when you leave the house, according to 2021 research published in Social Psychology.
Good habits help you keep up desirable behaviors over time since you’ll start to automatically perform them without having to rely on conscious motivation—something that’s notoriously fickle, according to the study.
Tracks Progress
Tracking your progress is the best way to see how far you’ve come and it’s also a great way to get a motivational buzz when you start seeing a difference in how you look, feel, and act. Progress tracking with a photo is one of the Hard 75 rules, so it’s built into the routine.
Gets You Active
Obviously, physical activity is a huge part of the challenge and a behavior many people struggle to maintain. If you’re doing 75 Hard, you’ll definitely get your daily movement in through the two 45-minute workouts each day.
Includes Time in Nature
While you don’t explicitly have to go on a nature walk, even cityscape fresh air and sunlight are better than nothing. Since the challenge requires you to complete one 45-minute workout outdoors each day, you’ll get benefits from sunlight exposure (which improves sleep), stress relief, and a brain boost.
Aside from giving up your favorite tasty snacks and foregoing a beer during the game, the 75 Hard Challenge has other practical issues.
Not for Everyone
Although 75 Hard has consistency built in, if you don’t include your own context cues for each habit you want to keep once the challenge is over, you likely won’t stick to it. In other words, if you don’t incorporate the habits into your everyday routine in a way that you’ll stick to once the challenge ends, you’ll probably revert to the same old habits—good or bad—that you were doing before. This is the exact reason why most people regain all the weight they lose during diets.
Easy to Overdo It
Without any actual professional nutritional or fitness guidance (Frisella is not a health expert), you can easily go overboard trying to meet the steep expectations of the challenge. You might not pair the ideal diet with your exercise program—such as a muscle-building calorie surplus with your hypertrophy training—unless you know what you’re doing.
You can accidentally choose habits that do more harm than good if you attempt high-intensity training alongside a low-carb diet or push past your body’s signals for rest in order to get in that second 45-minute workout.
Very Strict
Rigidity is the entire point of the 75 Hard Challenge. In fact, Frisella says in an interview with Megyn Kelly, “The whole point of the program is to put yourself in the most inconvenient, non-compromising situation that you possibly can,” with no room for substitutions.
He goes on to say that giving yourself a break or a “mental day” is a no-go because “letting yourself off the hook is the reason you are where you are in this state of unhappiness and unfulfillment.” If you get sick, sore, or have an emergency—too bad—you’ve failed.
Can Lower Confidence
Battering yourself into submission is not always the best for your mental health and certainly won’t work for everyone. Plus, not everyone who wants to improve their health is unhappy or unfulfilled.
In reality, positive thinking can boost self-confidence by helping you see challenges as temporary and conquerable. Overcoming setbacks and still working toward your health goals is a fast track to becoming more resilient and increases internal motivation and confidence. And for the record, internal motivation is stronger than the kind you’ll get from any challenge.
Final Verdict: What Do Experts Say About the 75 Hard Challenge?
As a personal trainer and nutrition coach, I believe that most people, even those with advanced fitness levels, shouldn’t attempt two workouts every single day. Combining cardio and strength training can interfere with recovery and overall results and is a recipe for burnout. Physically, mentally, and socially, two-a-day workouts can be draining and unsustainable and put you at risk of overtraining, which requires lengthy recovery.
If you’re set on following the two-workouts rule, make sure one is recovery-based—light yoga, walking, or stretching. Organized activities like jiu-jitsu or gym classes can count as one workout, with walking or something gentle for the second. For strength training, limit it to three to five days a week and always pair with recovery exercises.
I don’t recommend avoiding rest days, as even lighter workouts can be mentally exhausting and, on a practical level, can get in the way of other areas of your life, like relationships, work, and family responsibilities. Missing a session and starting over can feel defeating, which I’d never want for my clients. If you miss a workout you had intended to complete, it’s better to reassess and adjust instead of stressing over rigid plans.
In my opinion, the idea that “mental toughness” comes from strict workout rules is absurd. True consistency comes from internal motivation, doing what you enjoy for reasons that matter to you. Building skills in activities you love—whether yoga, strength training, running, or a new sport—will make you proud and boost your confidence in the long term.
Real toughness also means listening to your body. Sometimes, backing off is harder than following a rigid plan. Focus on consistency and finding joy in what you do rather than chasing the next challenge.
Why You Should Trust Us
I’m a certified personal trainer, strength and conditioning specialist, and nutrition coach, among other fancy titles—but my passion is communicating the countless benefits of being active and striving toward a healthier mind and body through attainable action. I use a hefty dose of science to guide the advice I give, along with the real-world experience I’ve gained over the last 15 years.
