Global Aging and Scientific Solutions by Lifestar

"Scientists Call for a Biomedical Apollo Project to Avert Global Aging Crisis" - The Demographic and Biomedical Case for Late-Life Interventions in Aging

Sources: Abstract: http://stm.sciencemag.org/content/2/40/40cm21.abstract via article "Scientists Call for a Biomedical Apollo Project to Avert Global Aging Crisis. Download the full article '40cm21.full.pdf' for $15 online or get it free if you give your email to Lifestar (see left) or read the Lifestar synopsis.

Numbers in brackets are references in the full article:

"In 2009 California-based LifeStar Institute asked biogerontologists Dr. Judith Campisi, Dr. Caleb "Tuck" Finch, Dr. Aubrey de Grey, Dr. George Martin, and Dr. Robert Butler.....

How far can the potential of new biomedical therapies to slow, arrest, or even reverse the damage of aging be brought to bear against the challenge of global graying?

They concluded:-

that an aggressive program of investment to realize that potential is not only justified, but necessary.

Full conclusions: “The Demographic and Biomedical Case for Late-Life Interventions in Aging,” (Published July 2010, Journal Science: Translational Medicine)

Aggressive biomedical research investments in new medicines to slow, arrest, and reverse the degenerative aging process are needed to turn a looming worldwide social calamity into an opportunity for a global renaissance of healthy longevity.

Degenerative aging process causes enormous human suffering, in age-related disease, disability, dependence, dementia, and death. Within a few decades, people that have been made sick, dependent, or unproductive by the damage of aging will outnumber the young and healthy. The diseases of aging will rob the world of some of our most productive citizens, and rapidly drive up the cost of healthcare and the budgets for public and private pensions.

The report highlights three key approaches to the challenge that must all be met to meet the goal of maintaining the health and productivity of today’s generations: 

(1) expand public health measures to help citizens avoid suffering prematurely from age-related disease; 

(2) develop new medicines that boost the body’s ability to maintain health and productivity longer by slowing down the degenerative aging process; and 

(3) use the principles of regenerative engineering, the special focus of SENS Foundation, to create therapies that remove, replace, repair, and neutralize the cellular and molecular damage that accumulates in aging bodies, and thus restore youthful structure and function to the tissues and lives of aging citizens.

To meet these goals, the report calls for targeted investments by the National Institutes on Health (NIH) and other public and private biomedical research organizations to bring forward new therapies against the degenerative aging process.

"In the case of late-life intervention in human age-related degeneration, what we can be certain of today is that a policy of “aging as usual” will lead to enormous humanitarian, social, and financial costs. Efforts to avert that scenario are unequivocally merited, even if those efforts are costly and their success and full consequences uncertain. The drive to tackle biological aging head-on must begin now."(1)

The Report

1. The Demographic and Biomedical Case for Late-Life Interventions in Aging. Michael J. Rae, Robert N. Butler, Judith Campisi, Aubrey D. N. J. de Grey, Caleb E. Finch, Michael Gough, George M. Martin, Jan Vijg, Kevin M. Perrott, and Barbara J. Logan Science Translational Medicine. 14 July 2010: 40cm21.

Edited

and highlighted

by Crabsallover
Draft

The Demographic and Biomedical Case for Late-Life Interventions in Aging
Abstract
The social and medical costs of the biological aging process are high and will rise rapidly in coming decades, creating an enormous challenge to societies worldwide. In recent decades, researchers have expanded their understanding of the underlying deleterious structural and physiological changes (aging damage) that underlie the progressive functional impairments, declining health, and rising mortality of aging humans and other organisms and have been able to intervene in the process in model organisms, even late in life. To preempt a global aging crisis, we advocate an ambitious global initiative to translate these findings into interventions for aging humans, using three complementary approaches to retard, arrest, and even reverse aging damage, extending and even restoring the period of youthful health and functionality of older people.

Introduction

Age is the greatest risk factor for most major chronic diseases in the industrialized world and to an increasing degree in the developing world. 

After adolescent development, functionality declines progressively with age (1), and mortality rates increase exponentially, doubling roughly every 7 to 8 years after puberty. AD is Alzheimers Disease.

The basis of the mortality lies in the progressive lifelong accumulation of deleterious changes in the structure of the body at the molecular, cellular, and tissue levels. These deleterious changes (aging damage) arise primarily as damaging side effects of normal metabolism, aggravated by environmental toxins and unhealthy lifestyle. Aging damage contributes to pathology either directly (by impairing the function of specific biomolecules) or indirectly (by eliciting cellular or systemic responses that generally serve near-term protective functions but ultimately are deleterious). As damage accumulates, organisms suffer progressively diminished functionality reducing the capacity to survive and recover from environmental challenge. These changes contribute to specific age-related diseases leading to increasing morbidity and mortality. 

Aging is plastic: Within a species, maximum life span is not fixed but can be increased by dietary manipulation [particularly CR calorie restriction] or genetic manipulation [particularly dampened insulin/insulin-like growth factor–1 signaling (IIS)]. These interventions generally reduce the generation, enhance the repair, and/or increase the tolerance of the molecular and cellular damage of aging preserving “youthful” functionality and reduce the incidence of age-related disease. 


There have long been calls for greater efforts to translate this research into clinical interventions to expand the healthy, productive period of human life. 

By targeting the aging damage that is responsible for the age-related rise in disease vulnerability, such interventions would reduce the incidence of most, if not all, age related diseases in unison, by modulating the underlying biology that drives them all, rather than treating each in isolation, as in conventional medicine. 

To date, however, investments in such research by the National Institutes of Health (NIH) and its international equivalents have been disproportionately low relative to their potential return; for example, the NIH $28 billion budget allocates 0.1% —perhaps as little as $10 million—to research on biological aging. Contrast this allocation with the costs of medical care for today’s aged, such as the current Medicare budget of $430 billion, and with projected outlays many times that number to treat future increases in the diseases of aging. 


Calls for an intensive agenda of research on the biology of aging have particular salience today because of two converging trends: one demographic and one scientific. 


Demographically, we are entering a period of unprecedented global aging, as the ratio of retired elderly to younger workers increases dramatically within the next decades in both developing and industrialized nations. 


Age-related disease and disability greatly increase medical costs, even when adjusted for survivorship, and are major determinants of the decline in productivity and labor force participation after midlife. Thus, the results of biological aging are both a rise in social costs and a decrease in a national workforce’s ability to produce the goods and services necessary to meet those costs. The costs of global aging to individuals and societies are therefore high and are projected to inflate into an unprecedented economic and social challenge in coming decades. 


Scientifically, this phenomenon coincides with the first robust reports of effective interventions into the biological aging of mammals that are already in late middle age when treatment begins. In 2004, Calorie Restriction was first shown to extend life span in mice as old as 19 months, which is broadly equivalent to the current average age of postwar “baby boomers.” And 2009 saw the first demonstration of pharmacological intervention into the biological aging of similar aged mice, with preliminary evidence of delays in cancer incidence and other changes in gross pathology.


Intervention in the degenerative aging process need only lead to a simple delay in the appearance of age-related disability and rising medical costs in order to alleviate the projected social costs and challenge of global demographic aging. This alone would increase the ratio between productive workers of all ages and the dependent frail elderly, simultaneously expanding the resources available to bear the costs of supporting a subpopulation of frail elderly and reducing the relative size of that subpopulation during the critical period of demographic transition. The benefit to be gained from intervention in biological aging would be even greater, however, if it were able to not only delay the onset but reduce the absolute ultimate burden of age-related disease. Preliminary evidence from animal models of retarded age-related degeneration and the identification of human subpopulations characterized by extreme survivorship with surprisingly little morbidity (possibly indicative of a phenotype of slow biological aging) suggest that such intervention might have this even more beneficial effect. Whether it would actually do so, however, is uncertain. 


Preliminary glimpses of the benefit to be anticipated from therapeutics targeting the underlying degenerative aging process can be gleaned from two studies performed a quarter-century apart (15, 16). Recently, Manton et al. (15) demonstrated that, by improving the health of older adults, investment in conventional medical technology in the late 20th century buffered projected declines in labor force productivity and thereby contributed significantly to economic growth. Such investment thereby constrained the growth of health care costs as a share of gross domestic product, effectively paying for itself; the authors provide analysis to suggest that ongoing investments can be projected to continue to do so. Economic modeling performed independently in the 1980s (16) indicated that even greater economic benefits can be expected from interventions that successfully slow the rate of biological aging. But this analysis is probably an underestimate, because it preceded and does not factor in the rapid rise in dependency ratios that lies ahead today, the alleviation of which represents a significant part of the benefits now projected to be realized by expanding investment in even conventional medical technology (15). Incorporating this new demographic challenge into the analysis of the economic impact of interventions targeting the underlying degenerative aging process would clearly substantially amplify the benefits to be expected. In light of these convergent scientific and demographic phenomena, we advocate an intensive, dedicated, and focused R&D agenda by developed and rapidly developing nations globally, to devise interventions to restore and maintain the health and functionality of humans in late middle age and older. 


RESEARCH ROADMAP Our consensus is that a realistic path toward this goal exists, by targeting age associated changes that, based on existing research, are known or thought to be important primary components of human age-related degeneration and thus drivers of vulnerability to age-related disease. Here we outline such an agenda, focusing on targets that are likely to be biomedically tractable, even later in life, and would make efficient use of intellectual, capital, and temporal resources. 

We propose a global biological aging research agenda focused on the detailed understanding of the following overlapping core age changes and developing therapies for decelerating, arresting, and reversing them:

(i) the loss of proliferative homeostasis,

(ii) neurodegeneration,

(iii) somatic mutations in both nuclear and mitochondrial DNA,

(iv) nonadaptive alterations in gene expression,

(v) immunosenescence,

(vi) nonadaptive inflammation,

(vii) alterations of the extracellular milieu. 

See the supporting online material (SOM) for brief elucidation (contact Crabsallover for a free copy quoting '2-40cm21_SM.pdf'). 


To ameliorate age-related changes, we identify three broad modes of intervention that should be exploited in addition to ongoing conventional, disease-centered medical innovation: 
(i) reduction in exposure to environmental toxins and amelioration of other risk factors through improved public health; 
(ii) modulation of metabolic pathways contributing to age-related changes; and 
(iii) a more broadly conceived regenerative medicine, to embrace the repair, removal, or replacement of existing aging damage. 


The relative potential of these interventions and their combination is portrayed in Fig. 2, presented in terms of their ability to deliver the 7-year postponement of the onset of age-related degeneration identified recently by four prominent gerontologists (including one of us, R.N.B.) as a realistic medium-term goal of biomedical gerontology (7).

Public health and medical advancements. 
There remains substantial room to improve healthy life expectancy through improvements in public health and lifestyles (17), medical control of disease risk factors, and traditional disease-oriented medicine. However, we note their limitations in the late-middle-aged cohorts in whom intervention is most urgent. 


These improvements are most effective when applied relatively early in life, especially during development (18); in later life, the effect of environmental influences declines (19). In fact, age-related changes lead to paradoxical relationships between disease risk factors and outcomes in the elderly: The relationship between well-established risk factors—such as overweight, hypertension, and hyperinsulinemia—and adverse outcomes often declines in magnitude or even reverses relative to their relationship in younger people (20). The causes and implications of these changes are often unclear. 


Some may be the result of “reverse causation,” in which the causal relationship between two closely associated phenomena is mistakenly taken to be the reverse of what it actually is; for example, mild overweight in older adults is associated with longer life expectancy, which may not indicate a protective effect of excess weight but rather that thinness in older adults is often the result of medical conditions that themselves cause weight loss (such as cancer, chronic obstructive pulmonary disease, or depression) or of the cachexia (wasting syndrome) and sarcopenia (the loss of muscle mass, strength, and function) of aging (21). 


But others may represent genuine age-related changes in the causal relationship between a risk factor, its underlying metabolic basis, and clinical disease. This uncertainty creates potential for unintentional worsening of patient health through mismanagement of the risk factor. 


Improvements in public health and conventional medicine will therefore contribute primarily to the future health of currently young people rather than people already in late middle age and beyond. 


Modulation of the metabolic determinants of aging damage. Interventions that mimic the modulation of metabolic pathways influencing the rate at which aging damage accumulates in model organisms— such as pharmacological mimetics of CR and down-regulation of IIS—have thus far received more attention than alternative routes to postponing human agerelated degeneration (5). This avenue is undoubtedly promising, but we note possible limitations. Many of these promising interventions have been demonstrated in model organisms with simpler signaling systems than those of humans; the inbred laboratory strains of model species that have dominated research to date may create experimental artifacts; and whereas life-span extension is readily quantitated, effects on age-related functional decline (reduced health span) are difficult to assess and characterization is limited (6). Accordingly, the benefits of even faithfully translated interventions in the health and functionality of aging humans remain uncertain. Additionally, the modulation of metabolic pathways typically imposes substantial side effects in model organisms, such as impaired immunity, low bone mass, vulnerability to cold, and lower fertility. Rapamycin, a likely CR mimetic because its inhibitory effects on a nutrient-sensing pathway parallel those of CR and several longevity mutations, was recently shown (11) to extend life span in mice when first administered late in life. This drug is an immunosuppressant, induces hyperlipidemia in humans (which would only modestly affect mouse life span, because wild-type mice are not susceptible to atherosclerosis), and might interfere with normal brain function—none of which were assessed in the recent report. Finally, even if interventions that favorably modulate the metabolic origins of aging damage can be fully translated to humans and any deleterious side effects mitigated, there remains the progressively reduced efficacy of such interventions the later in life they are initiated. These interventions decelerate age-related decline but cannot arrest or reverse its course (22). 

Thus, even assuming full human translatability, a rough extrapolation from results to date (22) suggests that a CR mimetic might extend human life expectancy by 25 years beyond the 85-year life expectancy that would otherwise result from “aging as usual” if begun at weaning but only 9.3 years if begun at age 54.

Regenerative therapies.

A third mode of intervention in the degenerative aging process is to directly target age-related changes themselves, rather than their environmental and metabolic determinants. This is the goal of regenerative medicine, a term often limited to cell therapy and tissue engineering: replacing lost cells and tissues with versions that are new and structurally youthful to restore function. We propose to broaden its scope to include conceptually similar interventions targeting other age related changes. Where they are possible, regenerative therapies would have the advantage of being effective even after youthful functionality has been lost. This feature also implies simpler and more rapid clinical testing, because any effects will necessarily be more immediate and direct (23). Regenerative therapies are thus especially attractive because they have effects even when initiated late in life, when the body has already accumulated extensive age-related changes (23, 24).

Regenerative therapies, too, would have limitations.

Their effects would necessarily be segmental, specifically affecting changes linked to the particular damage that a given therapy repairs. Further, it is unclear whether such therapies could be developed to address all age-related changes, although proofs of concept exist and other potential interventions can be foreseen from existing developments (25, 26). It is possible that therapies of different types might be used complementarily. Whereas regenerative therapies are segmental, metabolic interventions (especially CR) are highly pleiotropic, decelerating many, if not all, degenerative aging processes. The two approaches could thus be synergistic, with metabolic interventions decelerating age-related degeneration systemically and regenerative therapies used to restore functionality in particular tissues more fully. If regenerative therapies strengthen the weakest links in the chain of age-related changes decelerated by metabolic modulation, a disproportionate increase in healthy life span might result (Fig. 2). POLICY PRIORITIES Funding. Recognizing the potential of this research agenda to avert enormous economic, social, and human costs, we advocate that substantial new investments be made by governments, while engaging and facilitating the participation of the biomedical industry. A previous proposal that included one of us (R.N.B.) as an author suggested that the United States invest $3 billion annually (<1% of the current Medicare budget) in a broadly similar agenda (7); we suggest that this funding level is inadequate to deliver interventions in time to avert demographic crisis. We therefore urge a larger investment, targeted specifically to late-life interventions, matched by other developed and developing nations in proportion to the means and demographic urgency of each. Regulatory changes. Because they would reverse existing age-related changes, the effects of regenerative therapies may be so rapid as to be amenable to direct testing for their effects on specific diseases in time frames similar to those of conventional medicines (23), allowing their evaluation in clinical trials within existing regulatory frameworks. However, new regulatory structures will also need to be developed for the unique features of this class of medicines, especially for interventions targeting modulation of the metabolic determinants of the rate of accumulation of aging damage, whose effects will be more global and will emerge more gradually. Regulatory agencies such as the U.S. Food and Drug Administration (FDA) should be charged with developing new guidelines for testing interventions that do not necessarily target a single specific disease but that retard, arrest, or reverse the structural degeneration and loss of functionality associated with aging. Preliminary meetings exploring a subset of such issues have occurred between geriatricians and FDA officials (27); they will need to be expanded into interdisciplinary working bodies drawing in experts in the basic biology of aging (particularly experimentalists with extensive experience in lifelong interventional studies in mammals) and translational medicine. The ability of an agent to extend life span and health span in mammalian models, based on evidence of a broad spectrum of health effects in rodent models with robust historical controls, should be evaluated as sufficient preclinical evidence of efficacy for clinical trials. For human testing, new surrogate outcomes will need to be designed that would offer evidence for parallel effects without necessitating a measurement of life span, such as the panels of nonspecific deficits used in cohort frailty studies (1), reducing the acceleration of total mortality rate over the course of 8 years (7), and the cautious use of metabolic changes observed in animal models that are thought to be mechanistically important to the observed deceleration of the rate of biological aging. We also advocate that regulatory agencies charge interdisciplinary panels with identifying age-related dysfunctions that are sufficiently well characterized to merit consideration as new licensable therapeutic indications (that is, medical conditions for which regulatory bodies will approve effective therapies for marketing). A pressing example is sarcopenia, which occurs even in master athletes and in which loss of mass is only one relatively reversible element. Sarcopenia is a major contributor to age-related frailty and adverse outcomes, ranging from loss of activities of daily living to institutionalization, fracture risk, and increased mortality. It is estimated to cost the United States $18.5 billion ($11.8 billion to $26.2 billion) per year (~$1.5% of total health care expenditures) in direct medical costs alone (28). Exercise and supplemental energy and protein consumption can increase muscle mass to a limited extent but do not address the degradation of myocyte and neuromuscular unit structure. Beyond this, clinicians can at best resort to non–evidence-based off-label use of medications, risky and minimally effective hormone therapies, or unregulated, putatively ergogenic dietary supplements. Yet because sarcopenia is not a licensable indication, no incentive exists to develop therapies specifically targeting it. New treatments targeting determinants of sarcopenia other than loss of muscle mass could greatly benefit the health and functionality of older adults, and expert panels should explore this and other causes of age-related disability as possible new licensable indications. We also advocate efforts to include more people over the age of 65 in clinical trials. Older adults are the largest consumers of prescription medications and have the highest prevalence of the diseases for which many drugs are indicated. Yet they are sorely underrepresented in clinical trials and are often perversely excluded from trials precisely because of their burden of other age-related disease. For example, an analysis of 3470 community-living older adults with possible or probable Alzheimer’s disease (AD) found that >90% would be precluded from participation in either of two trials for cholinesterase inhibitors, the main drug class approved to treat AD symptoms (29). Extrapolation of the results of trials performed in younger adults into older patients is fraught with potential artifacts because there are substantial differences in drug pharmacokinetics and in the range and severity of adverse reactions, because of primary and secondary agerelated changes. This exclusion of older people is a major problem in conventional medicine testing and will almost preclude the testing of agents whose purpose is to retard, delay, or reverse age-related changes in late life. In addition to implementing comprehensive reforms to address weaknesses in the existing system (proposals from the American Geriatrics Society and the American

The Future of Aging: Pathways to Human Life Extension, pub. August 2010

reposted from: Amazon.co.uk. 'Look Inside' for Contents, Index and sample pages. Price: £191

Chapter 1: Bridges to Life by Ray Kurzweil & Terry Grossman argues that we should adopt a bridge strategy to keeping healthy and extending healthy lifespan. Bridge 1 is things we can do right now including exercise, nutritional supplementation and caloric restriction CR ('...in rats optimal level of caloric restriction... is 2/3 of ad libitum feeding' & 'for humans eat 20% less calories than ad libetum'  eg 180 pound moderately active man uses 2700 calories ad libetum, a 20% CR diet is 2160 calories per day.)

Bridges 2 biotechnology and 3 Nanoscience will come later so we must use Bridge 1 strategies to have a chance of living long enough to benefit from later Bridges ('we are only 15 years from maturation of the second bridge'). This chapter reviews their 2009 book 'Transcend: 9 Steps to Living Well Forever'.

More life before death

reposted from: http://commentisfree.guardian.co.uk/michael_blastland_and_andrew_dilnot/2007/12/no_news_of_good_news.html

Something wonderful is happening: people are living longer, healthier lives. So why don't we hear more about it?

All Michael Blastland and Andrew Dilnot articles

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December 9, 2007 12:00 PM

The past week has brought three pieces of outstanding good news. One received a short grunt of media acknowledgment, the others not even that. Yet they tell us more about human wellbeing than any number of health scares, gone-to-the-dogs jeremiads or nightmare scenarios.

The first piece of news is that we are, yet again, shown to be living longer than ever. What's more, the typical lifespan is not just up, according to the latest data from National Statistics this week, but rising at an accelerating rate: we are adding extra years, faster. Men have taken only about four years to put on their latest year of life expectancy. Astonishing.

Especially heartening for those zipping through middle age is where the gains come from. In earlier periods, it was improved infant mortality: as fewer babies died, the average lifespan increased. Now it derives as much from life extended at the end as sustained at the beginning. A 65-year-old man in 1981 could typically expect to live to 78. A 65-year-old man today will typically make it to 82.

Humbug, say those who feel that more years of life will be life endured, or, as Auberon Waugh almost put it: nothing is worth a couple of extra years in a nursing home in Weston-super-Mare.

But this brings us to the second hallelujah.

On average, the extra years are turning out, for women, to be healthy years, and about three-quarters of them for men. This lengthening of the so-called "healthy lifespan", measured either by the way people report their own health, or by subtracting the number of years of long-term disabling illness, challenges the presumption that longer life must mean decrepit life. We're getting wrinkly, not crumbly.

Source: National Statistics

That could imply more good news about the effect of an ageing population on health costs. Often described as a time bomb, it might be less explosive than suggested by the worst-case scenarios, which simply take the cost of healthcare in the few years before death and assume the line goes on flying upwards as the population wrinkles. The more accurate model might be that costs do go up, but that it is the proximity of death that sends them soaring, not the addition of what turn out to be healthy years before death.

The third piece of news is that, fast as life expectancy is rising for women, it is rising even faster for men. For so long the laggards, they are now closing rapidly. We don't know why, but we can speculate. For example, it may be that fewer men work in industries that, sooner or later, killed them. It could be that more women are in paid work, or enjoying lifestyles more like men's and so becoming more like men in this respect too. But the data suggest that men's progress is speeding up, rather than women's slowing down.

These gains are mightily impressive, and probably reliable. We can measure well enough the ages at which people die. The margin of uncertainty around the figures is tiny, the trends unmistakeable.

Of course, it's always possible there'll be bad news just around the corner, and the trends will reverse. Accelerating gains in lifespan can't go on forever - can they? - or one day the end will be receding faster than our approach. But just for now, we live, and live a bit more, in extraordinary times.

Despite the unrelenting coverage of everything that's wrong with our health service, the toxic soup people supposedly live in, the wretchedness of our diet or the stresses of modern living, something very good indeed is also happening, and on a huge scale; it's just that few talk about it.

We do not argue that all is right with the world, that no one experiences poor standards of welfare, or dies too young. On the contrary, we recognise huge demands for further progress. We know the gains are far from equally shared, and that a healthy old age might still mean a relatively impoverished one. We see that longer lives mean, other things being equal, more people.

But the numbers are a useful glimpse of the bigger picture. They are testament to how much people are continually achieving - and will go on to achieve - to improve wellbeing. Contrast that with how well they recognise this achievement, and one can't help but wonder at the lack of proportion. Longer life doesn't seem to make us grateful.

The authors will be speaking at Wanstead Library, Spratt Hall Road, London E11 2RQ on Thursday December 13 at 7pm. For details email vivian@newhambooks.co.uk.

giving middle-aged people 30 extra years of youthful life

So there you have it. We will almost certainly take centuries to reach the level of control over aging that we have over the aging of vintage cars—totally comprehensive, indefinite maintenance of full function—but because longevity escape velocity is not very fast, we will probably achieve something functionally equivalent within only a few decades from now, at the point where we have therapies giving middle-aged people 30 extra years of youthful life.

More

End of Aging -The Next Great Paradigm Shift?

reposted from Daily Galaxy

September 05, 2007

End of Aging -The Next Great Paradigm Shift?

In his new non-fiction Amazon bestseller, Ending Aging, Aubrey de Grey, champions recent progress in genetics and calorie-restricted diets in laboratory animals that hold forth the promise that someday science will enable us to exert total control over our own biological aging and substantially slow down the aging process.

Aubrey de Grey is convinced that he has formulated the theoretical means by which human beings might live thousands of years -- indefinitely, in fact.

Like Francis Bacon, de Grey has never stationed himself at a laboratory bench to attempt a ­single hands-on experiment, at least not in human biology. He is a computer scientist who has taught himself natural science, and has set himself toward the goal of transforming the basis of what it means to be human.

Dr. de Grey, who holds a rare University of Cambridge degree on this basis of publications rather than classwork, believes that the key biomedical technology required to eliminate aging-derived debilitation and death entirely is now within reach —technology that would not only slow but periodically reverse age-related physiological decay, leaving us biologically young into an indefinite future—is now within reach.

In Ending Aging, Dr. de Grey and his research assistant Michael Rae describe the details of this biotechnology. They explain that the aging of the human body, similar to the aging of man-made machines, results from an accumulation of various types of damage. And, as with machines, this damage can periodically be repaired, leading to indefinite extension of the machine’s fully functional lifetime.

By demystifying aging and its postponement for the nonspecialist reader, de Grey and Rae systematically dismantle the fatalist presumption that aging will forever defeat the efforts of medical science.

The most realistic way to combat aging, de Gray suggests, is to rejuvenate the body at the molecular and cellular level, removing accumulated damage and restoring us to a biologically younger state. Comprehensive rejuvenation therapies can feasibly postpone age-related frailty and disease indefinitely, greatly extending our lives while eliminating, rather than lengthening, the period of late-life frailty and debilitation.

"The real issue," de Grey writes, "surely, was not which metabolic processes cause aging damage in the body, but the damage itself. Forty-year-olds have fewer healthy years to look forward to than twenty-year-olds because of differences in their molecular and cellular composition, not because of the mechanisms that gave rise to those differences. How far could I narrow down the field of candidate causes of aging by focusing on the molecular damage itself?"

Removing the causes of aging-related deaths will also eliminate all the suffering that aging inflicts on most people in the last years of their lives. Aging kills 100,000 people a day. Social concerns about the effects of defeating aging are legitimate but don’t outweigh the merits of saving so many lives and alleviating so much suffering.

"There are mutations in our chromosomes, of course, which cause cancer," de Grey muses. "There is glycation, the warping of proteins by glucose. There are the various kinds of junk that accumulate outside the cell (“extracellular aggregates”): beta-amyloid, the lesser-known transthyretin, and possibly other substances of the same general sort. There is also the unwholesome goo that builds up within the cell (“intracellular aggregates”), such as lipofuscin. There’s cellular senescence, the “aging” of individual cells, which puts them into a state of arrested growth and causes them to produce chemical signals dangerous to their neighbors. And there’s the depletion of the stem cell pools essential to healing and maintenance of tissue.

"And of course, there are mitochondrial mutations, which seem to disrupt cellular biochemistry by increasing oxidative stress. I had for a few years felt optimistic that scientists could solve this problem by copying mitochondrial DNA from its vulnerable spot at “ground zero,” within the free-radical generating mitochondria, into the bomb shelter of the cell nucleus, where damage to DNA is vastly rarer.

"Now, if only we had solutions like that for all of this other stuff, I mused, we could forget about the “butterfly effect” of interfering with basic metabolic processes, and just take the damage ITSELF out of the picture."

De Grey's call to action, writes Dr. Sherwin Nuland, clinical professor of surgery at Yale University School of Medicine and author of How We Die and The Art of Aging, "is the message neither of a madman nor a bad man, but of a brilliant, beneficent man of goodwill, who wants only for civilization to fulfill the highest hopes he has for its future.” An opinion darkly countered by Dr. Martin Raff, emeritus professor of biology at University College London and coauthor of Molecular Biology of the Cell: “Seems to me this man could be put in jail with reasonable cause.”

De Grey has formulated a wide-ranging plan for the comprehensive and eventually indefinite postponement of age-related physical and mental decline, named SENS (Strategies for Engineered Negligible Senescence). He is the organizer of an ongoing series of conferences and workshops that focus on the key biomedical research relevant to SENS, and he also oversees the Methuselah Foundation’s growing sponsorship of SENS research worldwide.

"For decades," de grey summarized, "my colleagues and I had been earnestly investigating aging in the same way that historians might “investigate” World War I: as an almost hopelessly complex historical tragedy about which everyone could theorize and argue, but about which nothing could fundamentally be done. Perhaps inhibited by the deeply ingrained belief that aging was “natural” and “inevitable,” biogerontologists had set themselves apart from the rest of the biomedical community by allowing themselves to be overawed by the complexity of the phenomenon that they were observing.

"To intervene in aging, I realized, didn’t require a complete understanding of all the myriad interacting processes that contribute to aging damage. To design therapies, all you have to understand is aging damage itself: the molecular and cellular lesions that impair the structure and function of the body’s tissues. Once I realized that simple truth, it became clear that we are far closer to real solutions to treating aging as a biomedical problem, amenable to therapy and healing, than it might otherwise seem."

Posted by Casey Kazan.

Related Galaxy posts:

The Story of a Biologist & the Extension of the Human Life Span
Pathway to Longevity Discovered
Can Humans Live to 1,000? Some Experts Claim We Can — Others Want to Prevent That
Darwin's Lab: Scientists on Brink of Creating Life
World's Oldest Living Microbes May Cast Light on Aging & Life on Mars
“Longevity Genes” Solve Centenarian Paradox
The "Blue Brain" & Human Consciousness -Scientists Create Artificial Brain
"Mind Children": Transhumanism & the Search For Genetic Perfection
“What is Life?” A New Breed of Robots Are Causing Scientists to Question

Video: Aubrey de Grey -Defeat of Aging

http://www.technologyreview.com/Biotech/14147/