reasonattlm

It is hard to cover everything related to longevity, given that there is a vast diversity of approaches, and a lot of work presently taking place.

https://www.agingbiotech.info shows how much work goes into just making lists for just the industry side of the house.

Read a few of the lengthy end of year posts at Fight Aging! to see just how much there is to comment on (e.g. https://www.fightaging.org/archives/2023/12/a-look-back-at-2... ), and Fight Aging! only covers an opinionated selection of the full spectrum of research and development.

The 16S rRNA sequencing you are referring to is now quite cheap and efficient. [1]

Viome is one of many companies offering this as a service. Viome isn't so good at giving you the underlying data, some of the others may be better; look at their example reports or ask their support. Ombre, BIOHM, Tiny Health, Floré, etc.

In terms of whether the add-on services they offer are valuable (tailored prebiotics / probiotics / diet advice based on their reading of the literature) I think only time and randomized controlled trials will tell. Not that any of these services have any incentive to run trials! But it may be a useful time-saver for a self-experimenter who would have been digging through the literature to try to come to the same conclusions on things to test.

[1] https://doi.org/10.1038/s41467-019-13036-1

It is interesting that they achieved any positive results with prebiotics. The animal study evidence suggests that these are weak interventions compared to fecal microbiota transplant (FMT) from a young individual or flagellin immunization. Weak in the sense that they don't last long for one dose, whereas both FMT and flagellin immunization are essentially years-long to permanent effects, and also weak in the sense of a small effect size on the gut microbiome and health measures compared to FMT and flagellin immunization.

In principle it should be possible to produce some sort of one-time high dose oral probiotic that produces results that are in the same ballpark for effect size and duration as FMT. In practice, it doesn't look like anyone is rushing to get that done, and it might turn out to be very expensive to manufacture 100-200+ distinct microbial populations into a probiotic mix. No-one seems to know whether it would take that many, or whether there are a lynchpin few dozen species one could focus on to get an 80/20 outcome. But that sounds like a question that could be answered in the next decade or two at the present pace.

We should treat this study and the discussion of the relevance of the results as being highly speculative.

Firstly, near all genetic variants that have been found to correlate with age in one study population fail to replicate in other study populations, and this is true of studies with cohorts consisting of thousands of individuals. The study here used a primary cohort of less than 100 individuals over the age of 100. This is ever the challenge in research focused on extreme old age: very few people make it that far. There was a secondary validation cohort of a few hundred centenarians, but I'm not sure that should increase our confidence in the data, given the existence of other studies that did much the same thing and still failed to replicate.

Secondly, given the identification of a genetic variant, near everything one can say about it is quite speculative in advance of much more detailed research into how exactly that variant changes cell behavior.

Lastly, the most robust data established to date on the contributions of genetic variants to human longevity, with studies pulling from very large national databases such as the UK Biobank, suggests that genetics has only a minor role to play. Lifestyle choices and exposure to pathogens are the dominant factors. In the case of long-lived families, cultural transmission of lifestyle choices relating to longevity seems a more plausible explanation than genetics, given the rest of the literature as it presently stands.

An entire article pondering regional differences in COVID-19 mortality and severity without saying anything about differing demographics of (a) aging and its comorbidities and (b) obesity and its comorbidities.

SARS-CoV-2 is severe in old people and obese people, and very few outside that demographic. Wealthy nations have a much higher obesity rate than poorer nations. The US has ten times the number of obese individuals than India, three times as many as Nigeria. Wealthy nations have a larger proportion of the population in older age cohorts. The US has five times as many 65+ people as Nigeria.

I have no idea why the media persistently chooses to avoid these points. The research community has been turning out review papers by the score to point out, very bluntly, that COVID-19 mortality falls near entirely on the old and the obese.

For a fairly inclusive list of longevity industry companies:

https://agingbiotech.info/companies

If you can get into an incubator lab space that isn't in a major market like SF or Boston, where the rents are insane, one can expect to set up a reasonable wet lab for most uses given $200k in equipment and reagent costs and a couple of months of time. Then expect $5-10k/month in operating costs outside of salaries.

Several research groups and companies are working on in vivo applications of cellular reprogramming. Since its discovery, reprogramming has been used to produce induced pluripotent stem cells from any other type of cell. That process has been found to reverse age-related changes in epigenetic patterns and mitochondrial function characteristic of cells in old tissues.

Introducing the factors capable of reprogramming cells into a living animal may produce effects akin to stem cell therapy by converting a small number of cells into induced pluripotent stem cells, followed by stem cell signaling that beneficially affects tissue health more broadly. Alternatively, many cells may have their epigenetic markers reset to a more youthful state without losing their identity to become induced pluripotent stem cells. Or both. Beyond this, there is certainly the threat of cancer or structural damage to tissue through the conversion of too many cells, and this class of therapy will require careful development to ensure safety, even as the mouse data continues to look quite interesting.

David Sinclair has been pushing an epigenetic-centric view of aging of late, with analogies to information systems and computing. The most interesting part of the the supporting work suggests that DNA repair of double strand breaks has the side-effect of driving alteration of the epigenome in characteristic ways with age. That will be an important connection between stochastic nuclear DNA damage and deterministic global effects throughout the body, should the evidence continue to hold up.

As this illustrates, however, epigenetic change is a downstream issue in aging, a reaction to events and a changing environment, not a first cause. Fixing it may or may not turn out to be particularly useful in the broader picture of aging, depending on exactly where it sits in the web of cause and consequence. As a comparable example, hypertension is a major downstream issue in aging. It is far removed from root causes such as cross-link formation and inflammation, but is also a proximate cause of many forms of further dysfunction, such as pressure damage to delicate tissues in the brain. Controlling hypertension without addressing its causes is both possible and beneficial - but the benefits are limited by the fact that those root causes are still there, chewing away at the body in a thousand other ways.

This interesting open access paper recently published reports on the effects of hyperbaric oxygen treatment on telomere length and cellular senescence in immune cells taken from blood samples. I use the word "interesting" quite deliberately, because that is exactly and all that this research is. The paper is appropriately formal and modest on that front, but this attitude doesn't extend to the rest of the publicity, unfortunately. When one runs a business based around offering hyperbaric oxygen treatment, one must make hay while the sun shines, and extract every last drop of marketing juice from every study funded. Hence there are media articles out there at the moment breathlessly telling us that hyperbaric oxygen treatment reverses aging. This is ridiculous, and only makes it harder for the better end of the longevity industry to make progress.

Per the paper, hyperbaric oxygen treatment causes average telomere length to grow by ~20% and markers of cellular senescence to decrease by ~35% in populations of circulating immune cells. This doesn't tell us that hyperbaric oxygen treatment is an amazing rejuvenation therapy, any more than the NAD+ and mitochondrial function data for exercise tells us that exercise is an amazing rejuvenation therapy. In both cases we already know the bounds of the possible. We know that these interventions don't turn older people into notably younger people. If we're calling exercise and hyperbaric oxygen treatment rejuvenation therapies, then the term "rejuvenation therapy" is meaningless.

What this does reinforce is the point that peripheral blood immune cell parameters can be very disconnected from the overall state of aging. We know that telomere length as assessed in these cells is a truly terrible measure of aging. Circulating immune cells are prone to large variations in the pace of celular replication in response to circumstances. Immune cells replicate aggressively when provoked by the presence of pathogens or other issues requiring a coordinated immune response. Telomere length shortens with every cell division in somatic cells: in immune cells, telomere length thus has a very wide spread across individuals, varies day to day, is just as influenced by infection status and other environmental factors as it is by aging. It is just not all that helpful as a measure of aging, and downward trends with age are only seen in the statistics for large study populations.

It seems plausible that the same is true of cellular senescence in immune cells. Cells become senescent when they hit the Hayflick limit on cellular replication. Throughout much of life, the senescence of immune cells is likely more determined by replication pace (and thus immune challenges, the burden of infection) than by aging. And that is before we even get to the point that the authors of this paper used a less than standard measure of senescence, one for which it is possible to argue that it may or may not actually be representative of the burden of senescent cells in immune populations. Overall this data is all interesting, but I suspect that it tells us more about the poor relevance of the metrics chosen to anything other than the deeper aspects of immune function.

If hyperbaric oxygen treatment removed ~35% of senescent cells throughout the body, it would already be well known as a reliable therapy for arthritis, a way to reverse chronic kidney disease, a way to suppress inflammatory conditions, and an effective treatment for numerous chronic diseases of aging. In mice, removing a third of senescent cells via senolytic drugs produces reliably large and beneficial outcomes, while hyperbaric oxygen treatment does not. So clearly it is not globally clearing senescent cells - and nor should any responsible party be trying to present reductions in senescent immune cells as indicative of global senolytic effects throughout the body. What is observed here is an effect limited to the way in which the immune system is functioning. There is some evidence for hyperbaric oxygen treatment to improve resistance to infectious disease such as influenza, and that is interesting in and of itself, but I feel that much of what is going on here is an attempt by certain parties to jump onto the longevity industry bandwagon, rather than responsibly focusing on a realistic view of what can be achieved with their chosen intervention.

Some of the more noteworthy lessons I have learned to date as a result of running a longevity industry biotech startup, most of which likely apply to any biotech initiative, were incorporated into the "Notes on Starting a Biotech Company" section of this document:

https://www.fightaging.org/pdf/how-to-start-a-biotech-compan...

We don't need to end biological aging, just control it. Let aging run, producing molecular damage in tissues, and periodically repair and reverse that damage such that people don't become physically old.

The SENS Research Foundation folk have on occasion talked about what they think is the most funding that can be run through the research community to produce progress. Something like $100m/yr for each of the seven areas of interest would be a ballpark upper limit before you start to run out of competent research groups to fund productively.

Once you have a candidate therapy, expect $150M to get it through trials. It is very challenging to guess at how many different therapies are needed. It might be a hundred different forms of treatment in the case of cleaning up persistent metabolic waste. Even in the case of single target problems such as senescent cell accumulation (just selectively destroy those cells), it may still be the case that ten or twenty different therapies are funded to take a run at that grail.

(Then for every therapy approved, budget the usual industry size for providing a service to 3 billion people once every few years. Most such treatments will be biologic and small molecule drugs that can be mass produced, and the ballpark for infrequent treatments that are well into their mature, cost-optimized stage of manufacturing seems to top out at $10k or so - but that may well get crushed down lower by the economies of scale in providing to the world at large, rather than to the less than 1% who have a specific condition. But this is a whole other analysis).

Any attempt to say too much more than I have above about the control of aging approach is challenging at this stage. Too much variance.

Dasatinib + quercetin has been shown in a clinical trial to remove senescent cells in humans in much the same way it does in mice [1].

High dose fisetin (i.e. take a whole bottle of the stuff at one go, not just a couple of pills) works about as well as dasatinib + quercetin in mice, but absent published results from the presently ongoing Mayo Clinic trial we're all dubious that will translate to humans, given how widely these sorts of compounds have been consumed, tested, and assayed [2].

Ditto piperlongumine.

Beyond that, there are any number of biotech startups developing senolytic immunotherapies, small molecules, gene therapies, topical cosmetics, etc. [3]

[1] https://doi.org/10.1016/j.ebiom.2019.08.069

[2] https://brain.forever-healthy.org/display/EN/Fisetin+Senolyt...

[3] http://agingbiotech.info/companies/

Still as relevant 15 years later, as we still live in a world in which aging can be addressed via the construction of rejuvenation therapies, but most people are simply disinterested in the prospect, the science, and doing anything other than crumbling, suffering, and dying like their parents and grandparents.

The one big difference between the present and 15 years ago: the first rejuvenation therapies worthy of the name now exist in the form of senolytic treatments that selectively destroy senescent cells. Pretty much everyone over the age of 50 should be taking them once a year or so, and would have a better life as a result. It makes the pathos of the situation somewhat greater than it was.

No, no, no.

This is just an argument for putting more effort into a failed strategy. The reason why we haven't made much progress towards extending healthy human life isn't because the disease state is complex, it is because the primary strategy adopted by the research community is to reverse engineer the disease state, and then work backwards towards its cause.

Typical project: pick away at a small chunk of the altered metabolism of [age-related disease of choice]. Find a proximate cause of pathology that has some small contribution to the whole - an altered gene expression level, say, something really, really far removed from root causes. Find a small molecule that adjusts expression. Publish. Patent. Tech transfer finds someone willing to tinker with that family of small molecules to have a short at achieving a small alteration in the disease state. Goes into trials, fails at phase II or phase III.

This happens constantly. It is the bulk of all medical research for age-related disease. It is pointless. May as well not happen. Applying computational prowess to this process won't make it any better. You'll just have a lot more low yield approaches that still do nothing more than tinker with proximate causes in late stage disease, and will do next to nothing for patients. (With the occasional success like statins, which produce the amazing-for-this-strategy result of a 22% reduction in mortality. You still die, just slightly less often).

The only practical way forward for age-related disease is to entirely reject this approach to medicine in favor of a much, much better one.

1) Infer the root causes of aging and best points of intervention (already done, several times over).

2) Fix one of those causes, in isolation.

3) Observe the results.

Steps 1-3 have been achieved for removal of senescent cells. The results in animal studies are absolutely amazing, robust, night and day better than anything else anyone has done for the treatment of aging and age-related disease. Reversal of scores of diseases and measures of aging, every lab can do it, replicated many, many times via numerous different approaches.

Everyone is now backfilling their models of age-related disease, their understanding of disease etiology, to add senescent cells. Because they are clearly an important cause.

Once Unity Biotechnology has stopped being silly about their subpar approach to senescent cell clearance, and the rest of the dozen or so companies have started their trials, we should expect those human trials to follow the same sort of pattern.

This is the way to make progress. Infer root causes, target root causes, figure out which work by trying them. Backfill your understanding of age-related disease based on new data.

My company, Repair Biotechnologies, is working on regrowth of the atrophied thymus via FOXN1 upregulation. We're at the preclinical stage of getting the vector and formulation into shape, and the start of tests in influenza exposure models in mice.

The atrophy of the thymus is a major reason why the adaptive immune system declines. The evidence from sex steroid ablation in prostate cancer patients strongly suggests it is possible to provoke the naive T cell component of the adaptive immune system into regenerating itself in a matter of months, provided that the thymus is restored to more youthful activity. Also evidence from the Intervene Immune trial with growth hormone (not advisable as a strategy, but congratulations to that team on getting interesting data) for the same proposition.

To be clear this is a years long process for Repair Biotechnologies that would see us into trials around 2022, but at some point fixing the aged immune system will and must become a practical concern. At that point, we'll all be a lot less concerned about pandemics of this nature, as the mortality and hospitalization rates will be much reduced.

There are other things that need to handled to restore all of the aged immune system: getting hematopoietic stem cells back into line and functioning properly, regenerative medicine for lymph nodes, some form of targeted destruction for malfunctioning immune cells. But each of these items will give incremental benefits on its own.

One of those hidden powers is the destruction of the aging brain. Senescence of glial cells appears to be quite important in the progression of neurodegeneration, as both a source of neuroinflammation and all of its woes, and a mechanism capable of more directly causing neuron death.

Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline - https://doi.org/10.1038/s41586-018-0543-y

Tau protein aggregation is associated with cellular senescence in the brain - https://doi.org/10.1111/acel.12840

Flushing out 'zombie cells' could help stave off Parkinson's, study suggests - https://www.theguardian.com/science/2018/jan/23/flushing-out...

Astrocyte senescence: Evidence and significance - https://doi.org/10.1111/acel.12937

The good news here is that the senolytic drug dasatinib crosses the blood-brain barrier and has been demonstrated to destroy senescent glial cells in animal models, and destroy senescent cells elsewhere in the body in human trials. The cheap dasatinib / quercetin combination should be trialed in Alzheimer's and Parkinson's patients, and the sooner the better.

Any bio* field can lead to working on treating aging; at undergraduate level you have tremendous flexibility as to which direction you take. For now build connections. Go to the conferences where industry meets science and meet people (Undoing Aging, Ending Age-Related Diseases, Longevity Therapeutics, Longevity Leaders, etc). Figure out who the people are you'd like to work with. Either for the corporate path of interning with companies working on aging, leading to a scientific position with one such company, or for the academic path of postgraduate work with a research who is doing something in aging that you find interesting.

A prediction: the generic, low-cost drug dasatinib, a senolytic that selectively destroys senescent cells and can pass the blood-brain barrier, will be the best Alzheimer's treatment of the next decade, starting just as soon as the Mayo Clinic gets around to running a trial for that rather than focusing on fibrotic disease.

https://doi.org/10.1111/acel.12840

"Tau transgenic mice with late stage pathology were treated with senolytics to remove senescent cells. Despite the advanced age and disease progression, MRI brain imaging and histopathological analyses indicated a reduction in total NFT density, neuron loss, and ventricular enlargement. Collectively, these findings indicate a strong association between the presence of NFTs and cellular senescence in the brain, which contributes to neurodegeneration."

https://doi.org/10.1038/s41586-018-0543-y

"Here we show a causal link between the accumulation of senescent cells and cognition-associated neuronal loss. We found that the a mouse model of tau-dependent neurodegenerative disease accumulates p16INK4A-positive senescent astrocytes and microglia. Clearance of these cells as they arise using INK-ATTAC transgenic mice prevents gliosis, hyperphosphorylation of both soluble and insoluble tau leading to neurofibrillary tangle deposition, and degeneration of cortical and hippocampal neurons, thus preserving cognitive function. Pharmacological intervention with a first-generation senolytic modulates tau aggregation."

I can't say as I like his take on the longevity industry. It is the take that will produce few meaningful advances, the "looking under the lamp because that's where the light is" way of approaching life. Just more marginally better drugs that do a little bit more than those of 10 years ago.

Sadly investors probably care very little from a financial position as to whether a drug works or not, as their exit usually happens somewhere between trials at Phase 1 and Phase 2. Earlier in the longevity market because it is hot.

I've put together Request for Startup lists for the longevity industry for the past few years, based on fairly detailed insight into the state of the science.

https://www.fightaging.org/archives/2019/02/request-for-star...

https://www.fightaging.org/archives/2017/12/request-for-star...

https://www.fightaging.org/archives/2016/12/request-for-star...

Because things move slowly in biotech, just about everything in these documents except for more senolytics is still valid.

And yet the risk increase for dementia for people with periodontitis is not large at 6% in a recent sizable study.

https://www.healthinaging.org/blog/periodontitis-may-raise-t...

Cancer research largely proceeds in the wrong direction, towards ever more personalization to mechanisms specific to one tiny fraction of cancer types, or tiny fraction of tumors in that cancer type. Then people are surprised at the low cost-effectiveness of the expenditure. Which is not to mention that cancers will cheerfully evolve around an attack on any mechanism not vital to their operation.

Insofar as anything needs hacking, it is this wasteful focus in the research community. The research community needs a dramatic refocusing onto mechanisms that cannot be evaded and which occur in most or all cancers. The canonical example is to interfere in telomerase and ALT telomere lengthening. That can't be evaded, and all cancers do it. Shut these things down and cancer stops. Any cancer, any type, any stage, using exactly the same therapy. Yet the amount of work in this area is tiny in comparison to projects that verge on personalized medicine per tumor.

From the SENS point of view [1] a number of the Hallmarks are downstream consequences of the causes of aging; e.g. epigenetic alterations are a reaction to molecular damage. Attempting to use those hallmarks as a place to intervene is doomed to achieve marginal benefits at best. You can't cure an age-related disease by patching over its late consequences.

Aging is a spreading tree of cause and consequence, emerging from a few root cause forms of damage. Intervene at later branchings in the tree, and you cover ever fewer downstream harms. It would be like trying to prevent a complicated iron sculpture from collapsing by propping up a few pieces here and there rather than by de-rusting/rustproofing the whole thing. Intervention as close to the root causes as possible is the only effective way forward, given how challenging it is achieve anything in medical biotechnology.

At the time the Hallmarks of Aging was published, it was noted for completely failing to reference any of the existing SENS literature, despite including some of the SENS line items such as senescent cell accumulation. The Hallmarks - and the related Seven Pillars of Aging [2] that seems to be less well promoted - would clearly not exist without more than a decade of aggressive advocacy within the scientific community for SENS and the treatment of aging, but the Hallmarks authors chose to behave as though that prior work never happened.

[1] https://www.sens.org/research/introduction-to-sens-research

[2] https://www.fightaging.org/archives/2014/11/the-seven-pillar...

There are a bunch of other things that can't be fixed by delivering youthful stem cell populations into tissues, such as the presence of garbage molecules in long-lived somatic cell populations. Even youthful tissue can't break down glucosepane cross-links, or remove senescent cells efficiently, etc. Replacing damaged stem cell populations with functional ones is just one slice of the full spectrum of rejuvenation therapies that will be needed. This is all laid out in quite a lot of detail in the SENS outline for how to bring aging under medical control.

https://www.sens.org/research/introduction-to-sens-research

Testing per batch is needed when ordering direct from any manufacturer. In my experience there isn't any real difference in quality and order fulfillment between Chinese and non-Chinese manufacturers when it comes to extracts and research chemicals, provided you stick with groups that have good reputations in Alibaba.

So all that caution that most people feel regarding Chinese manufacturers should be spread out a little more and applied to those closer to home as well.

The only human study providing a compelling reason to try nicotinamide riboside is the one showing a drop in blood pressure in hypertensive adults [1]. But this was a very small group of patients. If it does that in most people (which it may not) then that alone is a compelling reason to use it providing the price is low.

However, it isn't a compelling reason for the sizable expense of developing this outgrowth of sirtuin / calorie restriction research. That funding and person-years of researcher time could have gone towards far more effective programs such as senolytic development, or other SENS damage repair approaches to aging.

Not all NAD+ precursors are the same. The evidence in animal studies suggests that some (such as nicotinamide [2]) do basically nothing. The most effective approaches appear to be infusions, but they are not cheap.

Currently nicotinamide riboside is produced by one company in the US, and the retail price reflects that. If you do decide to take it for the long term at the dosage from the studies of 1g/day or so, it is considerably cheaper to order by the kilogram from Chinese manufacturers (plenty of manufacturers on Alibaba) and run the necessary mass spectrometry and other tests per batch to ensure quality (plenty of providers on Science Exchange).

While you are taking it, consider that this is small potatoes. It is a tiny effect in the grand scheme of things. Exercise has a larger and more reliable outcome. The research community should be doing better than this (and is in the case of senolytics) and people outside the research community need to become better at telling the difference between marginal and useful approaches to the challenge of aging.

[1] https://doi.org/10.1038/s41467-018-03421-7

[2] https://doi.org/10.1016/j.cmet.2018.02.001

The article falls a little far on the side of saying there is nothing wrong with a 60-something year old. There is a lot wrong with a 60-something year old. It might not yet rise to the level of constant debilitating pain and loss of basic function, but it is there, and accelerating. The high-functioning 60-something doesn't have great odds of becoming a high-functioning 70-something, or of continuing to evade cancer.

If a 20-year old had the skin and cardiovascular system of a high functioning 60 year old, they would be in and out of the hospital, and undergoing serious therapy to prevent a predicted death in their 30s.

Rejuvenation therapies are best applied in advance, when the damage of aging is low. Don't play the game of saying that a 60-something who can walk around without a cane is just fine. They are not just fine. They are candidates for every form of therapy we can build that repairs the molecular damage of aging.

Every 60-year should be taking senolytics today, right now, for example. Their good-for-a-60-year-old metrics would be greatly improved by doing so.

If a even a small fraction of the effort spent on trying and failing to cope with the realities of degenerative aging was spent on the current crop of plausible approaches to build medical biotechnologies that can reverse degenerative aging, then the world would be a much better place.

Aging has an monstrously high economic cost, and is probably the only area of medicine in which the ratio of that cost to the amount spent on R&D to try to reduce that cost is vanishingly small.

Immunity is the standard problem for most vectors for gene therapy. Viral vectors have neutralizing antibodies, liposomes get eaten by macrophages, and so forth. Minimizing this issue to the degree needed for a therapy to work is the subject of a great deal of effort over past decades, and ongoing today. It isn't a solved problem, but there are many incremental approaches that, when combined, can let therapies work well enough given good engineering and good fortune.

This is not all that important, save as a commentary on the fact that combinational treatments are not well explored in the research community. This is true throughout medicine, and not localized to aging research.

Why not all that important?

1) The current record for nematode life extension - without extending the dauer stage indefinitely, an approach that has no analogue in higher species - is a tenfold extension of life.

2) Stress response upregulation of the sort accomplished here has outcomes that diminish as species life span increases. Where we can compare directly, calorie restriction and growth hormone knockout, the result in humans is constrained to be no more than a few years of additional life. Anything larger would already have shown up in the data.

So why is it that the research and development community don't undertake combinatorial treatments to any significant degree? I blame regulation and intellectual property law. Those items combine to make it much harder to find and deploy potentially synergistic therapies than to just go and work on some new single therapy. Thus there is much more work on new single therapies than one finding combinations of existing therapies that might do much better than either on its own.

If that study was isocaloric, then good for them for adding some human data to the existing animal data.

I'll qualify my remark: most people who practice restricted eating hours in some way won't count calories or aggressively try to ensure they otherwise eat the same amount and type of food, and thus the mechanism for benefits will be largely that of calorie restriction.