Another year has passed, and here we find ourselves once again another twelve months deeper into the 21st century and all of its promised wonders. The Golden Age science fiction authors were gloriously wrong in their extrapolation of trends of energy use, computation, and medicine, predicting a 21st century of slide-rules, ubiquitous heavy lift capacity into orbit and beyond, and a world in which 60-year olds still had bad hearts and little could be done about it. Instead, energy turned out to be hard, while computation enabled the biotechnology revolution and the prospect of longer, healthier lives through radical advances in medicine. Expansion into space awaits while we focus instead on the small-scale of our cellular biochemistry.
The trend in human life expectancy over the long term continues upwards, despite the short term negative impacts of obesity. Yet there remains a strong need for advocacy for aging research and the development of novel therapies to target the mechanisms of aging, even as this field grows apace. The progression of aging remains incompletely understood and much debated even given the more extensive knowledge of fundamental forms of damage that cause aging. The mainstream of our culture has yet to adopt a war on aging as it adopted the war on cancer. The advocacy of the first two decades of this century continues, but changing over time. Noted advocacy organizations SENS Research Foundation and Lifespan.io announced that they would merge; the book "The Death of Death" is now available in English, finally.
In part there is change because, unlike the early 2000s, there is now a longevity industry worthy of the name. It is a part of the broader biotech industry, and subject to the same perverse incentives, direct costs of regulation, and other issues that ensure a very long, slow development cycle. The pace of progress is nowhere as fast as we'd like it to be, even setting aside the terrible biotech investment market of the past two years, and some advocates have shifted their focus to this problem. Nonetheless, the wheel turns. Some of us are even optimistic about the next few decades. Meanwhile, the more adventurous arms of various governments are starting to come to the table to support areas of development, such as better measurement of biological age via clocks and other means, that are well underway. Typically one should expect to see government support arrive late to the table, in low-risk, high-attention areas that are already a foregone conclusion and well on their way to that conclusion. Thus ARPA-H is now entering the field of measurement and clock development.
A growing list of therapies are in preclinical development, a few programs reaching into clinical trials. Even if too many of the therapies under development aim only to modestly slow the progression of aging, there are still a good many potential rejuvenation therapies focused on repair of damage. This year, Fight Aging! noted updates from Cyclarity and Repair Biotechnologies (a few times, including at the Rejuvenation Startup Summit 2024) on atherosclerosis, Mitrix Bio on mitochondrial transplantation, Kimer Med on their implementation of the DRACO antiviral technology, Lygenesis on human trials of liver organoid implants. If you're looking for a broad view of the longevity industry and its progress, Aging Biotech Info continues to be a great resource; see an early 2024 interview with the maintainer for some of the background.
Last year's retrospective focused on categories of age-related disease rather than the forms of age-related damage outlined in the Strategies for Engineered Negligible Senescence (SENS) proposals, and was both less helpful and much more onerous to assemble as a result, I feel. So this year it is back to the fundamental causative mechanisms of aging, plus a couple of extra categories to cover some areas of personal interest.
Cell Loss / Atrophy
One of the most evident, early examples of cell loss leading to atrophy is the aging of the thymus, and the consequent loss of immune function that follows. Efforts to produce regeneration of the thymus lapsed for some years in the mid to late 2010s, but are now a going concern once more - multiple biotechnology companies are working on thymic regrowth. Replacement of cells via transplantation is one of the plausible paths forward to comprehensive therapy addressing cell loss and tissue atrophy, even where these cell therapies are really just ways to deliver signal molecules that adjust the behavior of native cells to increase regeneration. Cost-effective cell therapies will need universal cells, however. Progress is occurring on this front, but it is slow. Cell therapy examples from recent years include the ongoing efforts to provide new motor neurons to Parkinson's patients, delivery of cardiomyocytes to the aging heart, and cell therapy to restore the aged and atrophied thymus.
Beyond cell therapy lies tissue engineering and transplantation of that engineered tissue. This is a field with great promise, but which continues to struggle with goals such as creating the vasculature needed to support tissues larger than a few millimeters in size and speeding up the process of bioprinting. Cells survive transplantation better when introduced as tissue or in artificial tissue-like structures; it is even possible to provide those structures alone without the cells. A liver patch of only extracellular matrix produces benefits, for example. Recent work on tissue transplants include: efforts to replace portions of the neocortex; a clinical trial using sheets of corneal cells to replace a damaged cornea.
The alternative is to provoke replication in existing populations, such as by increasing stem cell function, or reactivation of developmental processes for replication in cell populations that normally do not replicate all that much in adults. A better understanding of how aged stem cells become dysfunctional than is presently the case will almost certainly be needed. Inroads are made in model organisms, but this area of research has the look of a long way to go yet. Changes in the stem cell niche, the supporting cells surrounding stem cells, are likely important. From the past year, a few examples of producing new cells in situ: gene therapy to promote cardiomyocyte replication in a damaged heart; more gene therapy to promote regeneration of lost sensory hair cells; yet more gene therapy to trigger muscle growth via MYC-1 expression; upregulation of cyclophilin A and increased PF4 both improve hematopoietic stem cell function; efforts to discover regulators of stem cell exhaustion; a similar search for regulators of neural stem cell function.
Mutation and Other Damage to Nuclear DNA
Stochastic DNA damage is mostly harmless, taking place in cells with few replications left, or in unusued regions of the genome. But mutations to stem cells and progenitor cells can spread throughout a tissue, producing somatic mosaicism. It remains unclear as to how important this is to aging, but most of the evidence for some role emerges from clonal hematopoiesis of indeterminate potential, somatic mosaicism in immune cells. This may contribute to kidney disease and risk of stroke, for example. What can be done about DNA damage? This seems a tough problem, but some paths forward have been suggested. Recently, it was discovered that natural examples of very efficient DNA damage response mechanisms can feasibly be transferred between species.
Damage in the structure of nuclear DNA and its surrounding machinery may be more subtle overall than simply mutational alterations to DNA sequences. For example, DNA damage and the repair response to that damage can indirectly cause RNA polymerase II to stall more often in reading DNA, altering gene expression for the worse. A fair number of researchers remain skeptics as to whether random mutation contributes meaningfully to aging. But research in recent years now suggests that random DNA double strand breaks and the resulting repair processes may alter the epigenetic regulation of nuclear DNA structure to cause many of the characterisitc changes in gene expression observed in aged tissues. To the extent that this is the case, we might think of partial reprogramming, a way to reset epigenetic expression by exposing cells to the Yamanaka factors, as a rejuvenation therapy. Certainly, a steady flow of animal studies of targeted reprogramming appear to demonstrate benefits. In the vasculature, for example, reducing hypertension. Or in the brain, where it reverses loss of cognitive function and is protective in models of neurodegeneration.
Another interesting field of study involves transposons, DNA sequences left behind by ancient viral infections that are repressed in youth, but run amok in later life to copy themselves across the genome, causing mutational damage. It remains unclear as to what degree this mechanism contributes to aging, but the research community is in search of the causes of transposon activation in later life. Perhaps the most intriguing evidence supports an important role for degree of transposon activity to determine the differences in life span between breeds of dog.
Mitochondrial Dysfunction
The pure SENS view of mitochondrial dysfunction is that the important component of it arises from damage to mitochondrial DNA. Researchers recently built a new cell model to better assess this mechanism. This is distinct from a more general malaise of impaired mitochondrial function that arises from gene expression changes with age, impairing mitochondrial dynamics, function, and the quality control process of mitophagy. It also results in mislocalized mitochondrial DNA fragments that provoke a maladaptive inflammatory response. These changes may result from cycles of DNA double strand break repair and their effects on nuclear DNA structure, and thus are downstream of damage to nuclear DNA. It remains clear as to how far one can go in restoring lost mitochondrial function by only restoring youthful gene expression, or improving mitophagy. Improvement in mitophagy is actually quite hard to measure, and there is much debate over the existing data for age-related mitophagy decline. Mitophagy interacts with the fusion and fission of mitochondria, and researchers have shown that adjusting the balance of fusion and fission in either direction can extend life in nematode worms. Equally, greater fragmentation of mitochondria due to excessive fission appears pathological in mammalian tissue.
Mitochondrial dysfunction is known to be important in muscle aging, in the heart and elsewhere in the body, and may interact with chronic inflammation to produce sarcopenia. Failing mitophagy is implicated in neurodegeneration, as is the consequent loss of mitochondrial function, an important mechanism in the aging of the brain. Mitochondrial dysfunction is also implicated in atherosclerosis, making the vascular cell dysfunction characteristic of the condition that much worse. Mitochondrial dysfunction has a role in ovarian aging, and in dry eye disease.
Approaches to address age-related mitochondrial dysfunction include allotopic expression of mitochondrial genes in the cell nucleus, less vulnerable to damage, and a backup source of mitochondrial proteins to prevent mutational damage to mitochondrial DNA from affecting mitochondrial function. Progress on this is taking place, but slowly; most recently researchers have produced a mouse lineage to demonstrate that ATP8 allotopic expression safely rescues function in loss of function ATP8 mutants. Then there is also the prospect of transplantation of functional mitochondria harvested from cultured cells or donor cells, shown to improve muscle function. Partial reprogramming of cells from aged tissues via short-term exposure to the Yamanaka factors has also been shown to improve mitochondrial function in the course of resetting epigenetic patterns. In terms of more targeted approaches to upregulate mitophagy, researchers have looked for targets in the function of HKDC1 and TFEB, but most of the mitophagy-related effort is focused on supplement-like molecules and their derivatives, such as the various groups working on urolithin A. While there are potential ways to increase the manufacture of new mitochondria, it isn't clear that this sort of enhancement will help in the aged environment.
Extracellular Matrix Damage
Changes in the physical properties of tissue due to age-related damage to the molecules of the extracellular matrix can produce cascading consequences. This is particularly true of stiffening of blood vessel walls, a contributing cause of hypertension, which in turn damages the delicate tissues of the kidney. Relatively little work takes place on this aspect of aging, and this line item in the SENS list of forms of molecular damage that drive aging includes more than just changes in physical properties. Any change in the extracellular matrix might change cell behavior for the worse in some way. There is every reason to think that a lot of this sort of thing takes place in the aging body, and that we have only scratched the surface of an understanding of it.
Senescent Cells
Senescent cells accumulate with age. They produce inflammatory signaling that is harmful to cell and tissue function, and encourages other cells to become senescent. Replication stress in cell populations may be an underappreciated source of senescence in later life. It is possible to correlate mortality to circulating levels of some of those signal molecules. Researchers have connected this signaling to the cells's response to the mutational damage that occurs as cells enter the senescent state. The consensus in the research community is that senescence is a complex state, or collection of states, and we remain far from a complete understanding of senescence. There are debates over whether everything presently classed as a senescent cell is in fact a senescent cell, or whether most of what are currently thought to be senescent tissue cells are in fact senescent tissue resident immune cells.
Nonetheless, senescent cells are linked to many age-related conditions and declines, and a selection of research from just the last year is extensive: skin aging is always a popular topic, and worthy of many mentions in the context of the burden of senescent cells; osteoporosis, particularly following menopause; macrophage signaling induces senescence in aging bone tissues; the onset of Alzheimer's disease and, for different reasons, Parkinson's disease; neurodegeneration more generally, such as via an increase in senescent T cells, increase in dysfunctional microglia, or aged neurons re-entering the cell cycle to become senescent; the relevance to neurodegeneration is worth emphasizing twice, as there is considerable enthusiasm in the research community for the development of therapies targeting senescent cells in the brain; moving on, there is the impairment of chemotherapy effectiveness by senescent cells; loss of capillary density in aged tissues; endothelial dysfunction in the vasculature; impairment of macrophage tissue maintenance functions; disruption of adrenal gland function; declining kidney function; excess cholesterol inside macrophages in atherosclerotic plaque provokes their senescence, contributing to the formation of unstable plaques prone to rupture; macular degeneration of retinal tissue; the aging of the heart and vasculature leading to cardiovascular disease; the role of senescent cells in cancer is both positive and negative for the patient, making the use of senolytic therapies more challenging than in other contexts; senescent B cells affect the ability of the immune system to garden the body's microbiomes; the aging of the ovaries; liver aging; loss of capacity for hair regrowth; the development of osteoarthritis; the secondary harms that follow stroke.
The first senolytic therapy combining dasatinib and quercertin continues to produce mostly promising results in clinical trials, most recently in older women with osteoporosis. The variety of senolytic therapies under development continues to grow at a fair pace year over year. Senolytic CAR-T therapies and adoptive transfer of other immune cells will likely be too expensive to be practical in the broader aging population, but continue to demonstrate promise in animal models. The cancer field may adopt these immunotherapy approaches to target senescent cancer cells, however. Topical applications of senolytics for skin aging continue to be developed, including a topical formulation of navitoclax shown to clear senescent cells from skin in mice. Novel biochemistry potentially relevant to therapies targeting senescence continues to be uncovered: PKM2 aggregation; that senescent cells use immune checkpoints to evade attention from immune cells; further, high mobility group proteins may turn out to be good targets to suppress senescence; and PAI-1 appears important in the creation of senescent cells.
A range of flavonoids are senolytic to varying degrees, and new ones are discovered on a regular basis, such as 4,4′-dimethoxychalcone. Researchers would like to improve the efficiency of flavonoid senolytics via delivery in nanocarriers, or by engineering better versions of molecules such as fisetin. Further, attempts are underway to find other natural compounds that can replace the chemotherapeutic drug dasatinib in the dasatinib and quecertin senolytic combination. The class of PI3K inhibitors continues to produce senolytic compounds. More diligent mapping of the surface features of senescent cells also continues to yield new targets for new selective ways to kill these errant cells. Researchers have proposed searching for senolytic lipids, and discovered a few that kill senescent cells via ferroptosis. Antidiabetic SGLT2 inhibitors are senolytic in overweight mice, but this seems likely to have little effect outside the context of obesity and the pathological diabetic metabolism. High intensity exercise is technically senolytic, but at the point at which we are calling lifestyle interventions senolytic, I feel the word begins to lose its meaning. At the end of the day, senolytics are just one part of a greater toolkit of rejuvenation therapies that will have to be used in combination.
An alternative approach to senolytics, less well developed, is to find ways to shut down the inflammatory signaling produced by senescent cells. It isn't clear that this is going to be as useful or progress as rapidly, given the incompletely understood complexity of the mechanisms by which senescent cells generate inflammation - but people are certainly working on it! Approaches to this end from the past year include CISD2 upregulation and selective sabotage of citrate metabolism.
Intracellular and Extracellular Waste, Including Amyloids
The amyloid-β that accumulates with age in the brain is an antimicrobial protein. This may explain associations between persistent viral infection and Alzheimer's disease, in that greater production of amyloid-β allows more of it to misfold and aggregate to contribute to Alzheimer's pathology. Other causes of amyloid-β aggregation may include the metabolic disruption produced by excess visceral fat. Amyloid-β may cause blood-brain barrier leakage, and this might be as important as other aspects of its pathology, such as provoking chronic inflammation and inhibiting synaptic proteasome function. While the amyloid cascade hypothesis remains firmly in the driver's seat of research strategy in the matter of Alzheimer's disease, one still finds fundamental debates taking place, such as whether it is the amyloid-β or other proteins that coincide with amyloid-β causing pathology, and the degree to which significant harms precede evident symptoms. More positively, it seems that loss of brain volume resulting from anti-amyloid therapies is not actually harmful, but results from clearance of amyloid. After amyloid-β in the progression of Alzheimer's disease comes tau aggregation and more severe harm to brain tissue. Tau aggregation induces inflammatory dysfunction in supporting cells in the brain, and consequent damage to synapses.
TDP-43 aggregation is a more recently discovered form of proteopathy relevant to neurodegeneration, and is more common than previously thought. It may also contribute to Huntington's disease pathology. Researchers continue to delve into the mechanisms of TDP-43 pathology. Attention has been given to NPTX2 as a link between TDP-43 aggregates and cell death. Like amyloid aggregation, TDP-43 aggregation may extend beyond brain tissue into the vasculature. Harm resulting from TDP-43 is not the only recent discovery! DDX5 also appears capable of forming prion-like aggregates.
The misfolding and aggregation of α-synuclein causes Parkinson's disease. α-synuclein pathology appears to interact with lipid metabolism in the brain, a bidirectional relationship shaping the spread of a synucleinopathy such as Parkinson's disease. As is the case for other protein aggregates associated with neurodegenerative conditions, α-synuclein aggregates can be found outside the brain - in skin, for example, or in exosomes in blood, opening the possibility of early detection. Outside the brain, researchers also see amyloid aggregates encouraging calcification in the heart. While thinking of the whole body, I should also note what would in a better world be a large area of research, into clearing out the various forms of lingering molecular waste, some of it altered proteins, that accumulate in the lysosomes of long-lived cells to cause dysfunction in normal recycling processes. Very little work takes place here, however; a few research teams, a few preclinical programs. In some years nothing comes to notice. This was one of those years.
In terms of approaches to clear protein aggregates, manipulating the behavior of microglia in the brain seems promising. Inhibition of p16 works, for example, perhaps by reducing the degree of senescence in this cell population. Also interfering in the LILRB4-APOE interaction, or upregulation of CCT2 to promote aggrephagy. Alternatively, there is the approach of preventing astrocytes from crowding out microglia and blocking access to amyloid plaques. Amyloid-targeting anticalins have been suggested as a strategy. Amyloid-β clearance via immunotherapy (with meaningful risk of unpleasant side-effects) is now a going concern, with enough data for meaningful commentary on what it might imply. It continues to appear that the amyloid cascade hypothesis is correct, and clearing amyloid in late disease stages doesn't help all that much. There, the target protein aggregate is hyperphosphorylated tau, and numerous approaches are under development. A more recent example is a clever evolution of proteolysis targeting chimera (PROTAC) technology that encourages the dephosphorylation of hyperphosphorylated tau, reducing the pace of aggregration. Another approach is delivery of anti-tau intrabodies via mRNA therapies. Others are investigating TYK2 inhibition as a way to slow the pace of pathological tau phosphorylation. For α-synuclein pathology, researchers are exploring use of a bacterial peptide that inhibits aggregate formation and antisense oligonucleotides to inhibit α-synuclein protein expression.
Gut Microbiome
Age-related alterations to the gut microbiome might arguably be added to the existing categories of SENS as another form of damage. This could occur independently of other mechanisms of aging, existing as a fundamental form of damage, even given that it is likely largely downstream of immune aging when it does occur over time. Loss of anti-microbial peptides may be important in reducing the ability of the immune system to garden the gut microbiome, for example. The gut microbiome is noted to be distinct in long-lived individuals. Harmful changes to the microbiome can be catalogued, but are far from fully understood. Nonetheless, these changes can be reversed independently of other aspects of aging by fecal microbiota transplantation from young donors to old recipients, producing benefits such as extended life span in animal models - or the reverse when transplanting an old microbiome into a young animal. Icariin is another approach to improving the composition of the gut microbiome. Flagellin immunization also works, demonstrated to extend life in mice. Sustained calorie restriction and intermittent fasting may improve the gut microbiome, or at least slow its aging. It is possible that delivery of genetically engineered microbes may also achieve useful goals, but this is far from proven in practice.
Restoration of a youthful gut microbiome may treat neurodegenerative conditions such as Parkinson's disease, and mechanisms to explain that outcome include its effects on astrocytes in the brain. Importantly, a clinical trial showed no benefits of fecal microbiota transplantation to patient's with Parkinson's disease. While the misfolding of α-synuclein characteristic of the condition may start in the gut in many patients, induced by a dysfunctional microbiome before spreading to the brain, addressing the gut contribution is likely too little, too late once evident symptoms have started. Despite this data point, the limited clinical trial data in humans for modification the gut microbiome, even transiently, is generally supportive of greater efforts in this direction.
Evidence exists for the gut microbiome to contribute to life span and numerous specific aspects of aging via mechanisms such as increased chronic inflammation: longevity in rabbits correlates with the gut microbiome composition, as do physiological changes in aged mice; aging of the ovaries; aging of the musculoskeletal system; increased risk of arrhythmia; Alzheimer's disease, where a fair amount of effort is devoted to trying to identify distinct microbial populations in patients, which may include infectious pathogens; reduced grip strength indicative of sarcopenia and frailty; loss of hematopoietic stem cell function; old individuals exhibit a distinct fungal gut microbiome; aging of bone leading to osteoporosis, and identification of specific features of the microbiome that correlate with this aspect of aging; the lymphatic system likely plays an important role in trafficking microbes and microbial metabolites from the intestine to the brain to cause harm; a novel way in which the aging microbiome may cause harm is by increasing intestinal permeability, allowing digestive enzymes to leak into tissues; it may also promote thymic involution, accelerating immune aging; rheumatoid arthritis may be driven by a distinct gut microbiome; menopause and the composition of the gut microbiome have a bidirectional relationship.
Cryonics
At the present pace of development of rejuvenation therapies, every older adult is going to age to death. Cryonics, the low temperature preservation of the structure of the mind following clinical death, remains a necessary industry in waiting. It has yet to exist in any way meaningful to the vast majority of people. Yes, one can be cryopreserved. No, the protocols are nowhere near as robust as we'd like them to be, and there are too few cryopreservation organizations to save more than a tiny handful of people.
There is a clear and well-defined roadmap for the technological capabilities needed to reach the fully developed, vast cryonics industry of the future. The road to turning the present small non-profit cryonics organizations into a full-fledged industry to compete with the grave and oblivion most likely starts with reversible cryopreservation of organs for the transplant industry. Solve that problem, and there is an engine to bring funds and interest into tissue preservation more generally. We will find ourselves half-way to convincing the world that the same can and should be done for people on the verge of death, to preserve them for a future in which both the technology and the will exist to safely restore a body and brain from both crypreservation and the damage of aging.
Aging Clocks
While not under the SENS heading, it is interesting to keep an eye on the development of clocks to assess biological age - or at least which are claimed to assess biological age. It may be fair to say that meaningful progress towards rejuvenation therapies can only occur to the degree to which we can effectively measure aging. This, at least, is a consensus sentiment in the research community. That community produces new clocks at quite the pace. In just the last year: a novel proteomic clock; an aging clock built from the senescence-associated secretory phenotype of senescent monocytes; a clock built from the metabolome called MileAge; a clock built from cheek swab DNA methylation data; a clock built from brain MRI imaging data; more novel transcriptomic clocks; the development of organ-specific proteomic clocks; a clock based on retrotransposon DNA methylation; aging clocks built from retinal imaging data; a clock based on protein aggregation; a physiological aging clock using clinical biomarker data.
A growing body of clinical trial data includes clock measures, enough now to start to say something about how useful the mainstream clocks are in practice. Some would argue it is time to stop building new clocks and standardize on the best of the established clocks. While epigenetic age acceleration in many clocks correlates well with age-related disease and mortality, a fair number of issues remain to be overcome. Existing clocks have many quirks, such as being responsive to psychological stress or time of day. Clock data is obtained from immune cells in a blood sample, and different immune cell populations exhibit different patterns of epigenetic aging, biasing results. This is also true when considering differences between mammalian species. Work on correcting this issue has led to the concept of intrinsic epigenetic age. Nonetheless, blood sample clocks do not generalize well to other tissues. The greatest challenge, however, is how to understand how the measured changes making up the clock actually relate to underlying processes of aging and disease. Some inroads are being made, such as separating harmful from adaptive changes and understanding how much of what is measured is epigenetic drift.
Other novel work on clocks this past year included: improvements to the Pace of Aging clock; advocacy for clocks built on clinical biomarkers and risk factors; a better grasp as to how lifestyle choices affect epigenetic age; demonstrating that modern clocks do show a slowing of aging for people exhibiting greater physical fitness; continued research into glycosylation clocks; quantifying the level of uncertainty we should expect from clocks that assess biological age; noting that chronic liver disease accelerates epigenetic aging in other organs; the negligibly senescent axoltl exhibits little alteration in the methylome over its lifespan, making it hard to construct something resembling the epigenetic clocks established for mammals; relating the existence of epigenetic clocks to theories of programmed aging; demonstrating that acccelerated aging correlates with cardiometabolic disease; Olympic medal winners exhibit slower expigenetic aging in comparison to other competitors; a demonstration that more recent epigenetic clocks do correlate with Alzheimer's disease risk.
Articles
Every year I note that I am not writing as much as I used to, or at least not directing said writing in the direction of the Fight Aging! audience as much used to be the case. There are more demands on my time than there used to be, or so it seems. Still, a few items from the past year are noted below.
- Predicting the Order of Arrival of the First Rejuvenation Therapies
- Reporting on a Nine Month Self-Experiment in Taurine Supplementation
- Request for Startups in the Rejuvenation Biotechnology Space, 2024 Edition
- Notes from the Rejuvenation Startup Summit in Berlin, May 2024
At the End, the Wheel Turns
The more involved one is in the field of aging and longevity, the more one feels that the tremendously important work of building therapies to treat aging as a medical condition is crawling along at a very slow pace indeed. But step back, look in only every five years or so, and change is rapid. Progress is made. The wheel turns. It can never be fast enough in a world in which so very many people suffer and die from age-related disease each and every day, but this is a very different environment when compared to the state of affairs twenty years past. The 2040s will be amazing.
View the full article at FightAging
