The first hint comes from the Mayo Clinic’s Darren Baker. Baker has developed a way of delaying symptoms of old age in mice, and has even been able to reverse some signs of aging in already aged mice. Here’s more:

Baker has developed a way of killing all of a mouse’s senescent cells by feeding them with a specific drug. When he did that in middle age, he gave the mice many more healthy years. He delayed the arrival of cataracts in their eyes, put off the weakening of their muscles, and held back the loss of their body fat. He even managed to reverse some of these problems by removing senescent cells from mice that had already grown old. There is a lot of work to do before these results could be applied to humans, but for now, Baker has shown that senescent cells are important players in the ageing process.

Note that the mice in this study didn’t live any longer; they just spent more of their life being healthy.

Baker exploited the fact that many senescent cells rely on a protein called p16-Ink4a. He created a genetic circuit that reacts to the presence of p16-Ink4a by manufacturing an executioner: a protein called caspase-8 that kills its host cell. Caspase-8 is like a pair of scissors – it comes in two halves that only work when they unite. Baker could link the two halves together using a specific drug. By sneaking the drug into a mouse’s food, he activated the executioners, which only killed off the cells that have lots of p16-Ink4a. Only the senescent ones get the chop.

Baker tested out this system in a special strain of genetically engineered mice that age very quickly. It worked. The senescent cells disappeared, and that substantially delayed the onset of muscle loss, cataracts, and fat loss. Typically, around half of these mice show signs of muscle loss by five months of age. Without their senescent cells, only a quarter of them showed the same signs at ten months. Their muscle fibres were larger, and they ran further on treadmills. Even old mice, whose bodies had started to decline, showed improvements. _Discover

Another look at this research from the Economist:

Dr Baker genetically engineered a group of mice that were already quite unusual. They had a condition called progeria, meaning that they aged much more rapidly than normal mice. (A few unfortunate humans suffer from a similar condition.) The extra tweak he added to the DNA of these mice was a way of killing cells that produce P16INK4A. He did this by inserting into the animals’ DNA, near the gene for P16INK4A, a second gene that was, because of this proximity, controlled by the same genetic switch. This second gene, activated whenever the gene for P16INK4A was active, produced a protein that was harmless in itself, but which could be made deadly by the presence of a particular drug. Giving a mouse this drug, then, would kill cells which had reached their Hayflick limits while leaving other cells untouched. Dr Baker raised his mice, administered the drug, and watched.

The results were spectacular. Mice given the drug every three days from birth suffered far less age-related body-wasting than those which were not. They lost less fatty tissue. Their muscles remained plump (and effective, too, according to treadmill tests). And they did not suffer cataracts of the eye. They did, though, continue to experience age-related problems in tissues that do not produce P16INK4A as they get old. In particular, their hearts and blood vessels aged normally (or, rather, what passes for normally in mice with progeria). For that reason, since heart failure is the main cause of death in such mice, their lifespans were not extended.

The drug, Dr Baker found, produced some benefit even if it was administered to a mouse only later in life. Though it could not clear cataracts that had already formed, it partly reversed muscle-wasting and fatty-tissue loss. Such mice were thus healthier than their untreated confrères. _Economist

This research will require replication and a great deal of clarification, before it moves from mice to larger mammals such as humans. But it opens up a number of possible avenues of research.

The second hint of likely means to achieve healthier long lives, is research done in fruit flies at the Salk Institute, in southern California.

Although it is a well-documented fact that restricting calories during daily food intake is the easiest strategy to extend life spans for both humans and animals, little is known about biological mechanisms underlying this phenomenon.

…”Fruit flies and humans have a lot more in common than most people think,” said Leanne Jones, an Associate Professor at Salk’s Laboratory of Genetics and a lead scientist on the project, “There is a tremendous amount of similarity between a human small intestine and the fruit fly intestine.”

The researchers found that boosting the activity of dPGC-1, the Fruit Fly version of the gene, resulted in greater numbers of mitochondria and more energy-production in flies; the same phenomenon is seen in organisms on calorie restricted diets.

When the activity of the gene was accelerated in stem and progenitor cells of the intestine, which serve to replenish intestinal tissues, these cellular changes correspond with better health and longer lifespan.

The flies lived between 20 and 50 percent longer, depending on the method and extent to which the activity of the gene was altered. _ibtimes

The fruit fly research suggests that not only healthier long lives are possible, but “longer long” lives are possible as well.

The approach taken by the SENS Foundation involves using multiple approaches to extending healthy lifespan. Destroying senescent cells — such as Darren Baker is learning to do — is one of the main approaches that SENS is following. Improving the function of mitochondria is another of the main tactics of SENS.

As humans in advanced societies are putting less and less energy into raising children, and putting more and more energy into raising themselves, thoughts of increased longevity and lifespan are coming more into the mainstream of respectability. The main limitation to further research into life extension is — as always — funding. But even with unlimited funding, moving the research from animal models into human therapeutics would take a matter of decades.

Al Fin Longevity

Two recent computational studies show that expression relationships between genes change with age – for example, some genes have expression levels that are highly correlated in early adulthood but not in old age. Both studies propose new methods for identifying gene groups with this behaviour, and the second also makes a compelling case that many related genes lose coexpression with age. Crucially, the correlation between a pair of genes may change with age even when the average expression levels of both genes do not – so these new coexpression methods are complementary to traditional differential expression analyses of microarray data.

Gillis et al. developed a new framework for identifying pairs of genes differentially coexpressed with age that is based on Haar wavelets, and tested it on a large set of human expression data mined from the handy GEMMA database. Unlike other methods that can interpret data coming from only two groups (e.g. young mice vs. old), the new wavelet method is designed to handle multiple ordered groups – such as animals of many different ages. The authors don’t discuss the biological implications of their results in any detail, instead promising these will be explored in a later paper.

Southworth et al. showed that coexpression patterns of groups of related genes become less coherent as animals age. Using several different methods for grouping genes together (e.g. assigning genes to the same group if they share a function, or if they are targets of the same transcription factor), they calculated intra-group correlation in 16- and 24-month-old mice using data from the AGEMAP study. They identified a surprisingly large number of groups with lower correlation in old mice. One of these is the targets of NF-κB – a transcription factor that, when knocked down, can reverse skin aging. Only a few groups (including one enriched for DNA damage genes) showed higher correlation in old mice. Also, the authors found that genes showing decreases in correlation aren’t randomly located on the chromosome – instead, they form several clusters.

What are the causes and consequences of these changes in gene group correlation? Previous single-cell studies have shown that transcriptional noise, or cell-to-cell variation in the expression levels of individual genes, increases with age. Clearly transcriptional noise is going to affect coexpression to some degree: any increase in a gene’s noise level will automatically reduce its calculated coexpression with other genes. But changes in coexpression can also occur without any corresponding change in noise. These changes may reflect cellular processes that are active or suppressed at different times of life, and many or all such changes (such as a ramped-up DNA damage response in old age) may be adaptive. Further analyses are needed to tease out which age-related coexpression differences result from noise, and which ones are telling us something new.

Gillis, J., & Pavlidis, P. (2009). A methodology for the analysis of differential coexpression across the human lifespan BMC Bioinformatics, 10 (1) DOI: 10.1186/1471-2105-10-306

Southworth, L., Owen, A., & Kim, S. (2009). Aging Mice Show a Decreasing Correlation of Gene Expression within Genetic Modules PLoS Genetics, 5 (12) DOI: 10.1371/journal.pgen.1000776

Ouroboros

“Signs of aging were erased and the iPSCs obtained can produce functional cells, of any type, with an increased proliferation capacity and longevity,” explains Jean-Marc Lemaitre who directs the Inserm AVENIR team….The age of cells is definitely not a reprogramming barrier. _SD

Cell Rejuvenation via IPSC
Scientists at the Functional Genomics Institute have taken cells donated by persons older than 100 years, and reprogrammed these senescent cells into pluripotent stem cells and embryonic stem cells. These stem cells can then be differentiated into specialised cells for cell, tissue, and organ replacement therapy — once the details are worked out.

The researchers have successfully rejuvenated cells from elderly donors, some over 100 years old, thus demonstrating the reversibility of the cellular aging process.


To achieve this, they used an adapted strategy that consisted of reprogramming cells using a specific “cocktail” of six genetic factors, while erasing signs of aging. The researchers proved that the iPSC cells thus obtained then had the capacity to reform all types of human cells. They have the physiological characteristics of “young” cells, both from the perspective of their proliferative capacity and their cellular metabolisms.


Researchers first multiplied skin cells (fibroblasts) from a 74 year-old donor to obtain the senescence characterized by the end of cellular proliferation. They then completed the in vitro reprogramming of the cells. In this study, Jean-Marc Lemaitre and his team firstly confirmed that this was not possible using the batch of four genetic factors (OCT4, SOX2, C MYC and KLF4) traditionally used. They then added two additional factors (NANOG and LIN28) that made it possible to overcome this barrier.


Using this new “cocktail” of six factors, the senescent cells, programmed into functional iPSC cells, re-acquired the characteristics of embryonic pluripotent stem cells.
In particular, they recovered their capacity for self-renewal and their former differentiation potential, and do not preserve any traces of previous aging. To check the “rejuvenated” characteristics of these cells, the researchers tested the reverse process. The rejuvenated iPSC cells were again differentiated to adult cells and compared to the original old cells, as well as to those obtained using human embryonic pluripotetent stem cells (hESC).


…The results obtained led the research team to test the cocktail on even older cells taken from donors of 92, 94 and 96, and even up to 101 years old. “Our strategy worked on cells taken from donors in their 100s. The age of cells is definitely not a reprogramming barrier.” He concluded. “This research paves the way for the therapeutic use of iPS, insofar as an ideal source of adult cells is provided, which are tolerated by the immune system and can repair organs or tissues in elderly patients.” adds the researcher.


…Inserm’s AVENIR “Genomic plasticity and aging” team, directed by Jean-Marc Lemaitre, Inserm researcher at the Functional Genomics Institute (Inserm/CNRS/Université de Montpellier 1 and 2) performed the research. The results were published in Genes & Development on November 1, 2011 _SD

The first use of this new regenerative technology is likely to be cell replacement therapy. But as the methods for growing replacement tissues and organs in the lab are perfected, the methods should be suitable for producing cells to use in growing replacement tissues and organs for purposes of disease treatment and for treating senescence.

Cross-posted from Al Fin

Al Fin Longevity

The ongoing study of current cognitive enhancers such as those in the table above, have given us scattered hints as to what future therapies might offer. Here is a short list of possible future targets for cognitive therapies:

Among targets under investigation, cholinergic receptors have received much attention with several nicotinic agonists (α7 and α4β2) actively in clinical trials for the treatment of AD, CIAS and attention deficit hyperactivity disorder (ADHD). Both glutamatergic and serotonergic (5-HT) agonists and antagonists have profound effects on neurotransmission and improve cognitive function in preclinical experiments with animals; some of these compounds are now in proof-of-concept studies in humans. Several histamine H3 receptor antagonists are in clinical development not only for cognitive enhancement, but also for the treatment of narcolepsy and cognitive deficits due to sleep deprivation because of their expression in brain sleep centers. Compounds that dampen inhibitory tone (e.g., GABAA α5 inverse agonists) or elevate excitatory tone (e.g., glycine transporter inhibitors) offer novel approaches for treating diseases such as schizophrenia, AD and Down syndrome. In addition to cell surface receptors, intracellular drug targets such as the phosphodiesterases (PDEs) are known to impact signaling pathways that affect long-term memory formation and working memory. Overall, there is a genuine need to treat cognitive deficits associated with many neuropsychiatric conditions as well as an increasingly aging population. _Source

It is important for us, at the outset, to take as realistic a viewpoint toward the possibility of meaningful cognitive enhancement as possible. The Likelihood of Cognitive Enhancement (Lynch et al 2011 PDF) is a useful introduction to many of the practical issues that need to be faced from the very beginning of this enterprise. Cognitive Enhacement: Promises and Perils (Hyman 2011 PDF) is a less technical introduction to the topic, perhaps more accessible to most laymen.

Cognitive Enhancement as a Pharmacotherapy Target for Stimulant Addiction (Sofuoglu 2010) looks at the use of cognitive enhancers as possible treatments for cocaine and methamphetamine addictions. Long term and heavy use of these drugs leads to cognitive deficits which make it even more difficult for a person to stop using these drugs and lead a “normal” life. The restoration of cognitive function is likely to provide a certain amount of “mental fortification” to allow at least some addicts to turn away from the dead end lifestyle. Similarly, restoration of cognitive function in persons suffering from age-related neurodegeneration is more likely to allow the person to participate in normal social interaction, and to undertake some level of responsibility, and perhaps productive activity.

Emerging Pharmacotherapies for Neurodevelopmental Disorders (Wetmore et Garner 2010) looks at the use of cognitive enhancers for persons who suffer from neurodevelopmental disorders such as Down’s Syndrome, Fragile X, autism, etc. Given the overlap of mechanisms between some of the cognitive deficits in developmental disorders and ageing-related cognitive deficits, some of the coming developments in this area of pharmacotherapy should also prove quite helpful for treating age-related dementias.

As more is learned about the time-course of dysfunction in NDDs [neurodevelopmental disorders], targeting of therapies to the existing brain state may be improved. Moreover, individuals with NDDs have multiple cognitive and behavioral disabilities, and a particular drug therapy may improve only a subset of cognitive functions. Thus, a combination of complementary drugs may offer the most benefit by addressing deficits in attention, arousal, information processing, or depression.
…
The NDDs discussed here are phenotypically diverse yet linked by common mechanisms of dysfunction, including abnormal gene dosage, imbalance among neurotransmitter systems, and local protein translation (Fig. 2). A particular NDD can be caused by mutations in multiple genes, underscoring the convergence of dysfunction in key biochemical pathways. _Source

Finally, I would like to append to this entry some material from an earlier Al Fin article, which provides a few hints of future drug targets, as well as links to related material:

AMPAkines
CREB
PDE Inhibitors(4,10)
Nicotinic Alpha-7 agonists
mGluR antagonists
5HT6 antagonists

Frontrunners in the pharmaceutical race for smarter, better memory drugs include Memory Pharmaceuticals, Cortex Pharmaceuticals, Saegis Pharmaceuticals, Helicon, Lilly, Pfizer, Wyeth, Merck, Sention and many others. The precedent of approving drugs for erectile dysfunction (ED)–a lifestyle drug–suggests that smart drugs will eventually be approved for drooping memories as well.

Further Reading:

Molecules for Memory

Nootropics

Smart Drugs: What Are the Prospects?

Shaping the Brain with Smart Drugs (Gazzaniga)

CREB and Memory (basic neuroscience)

CREB, Synapses, and Memory Disorders

Hat tip Advanced Nano and Kurzweilai.net

Al Fin Longevity

the naked mole rat has what could be the most extraordinary set of natural defenses ever found in a mammal. A mouse’s life is short and terrible—even in the lab, with plenty of food and a steady thermostat, it lasts for just three or four years at the most. A naked mole rat shows no sign of aging until it’s a quarter of a century old. Blind and plump, it skitters around in a hazmat suit of its own creation. _Slate

Naked mole rats appear impervious to radiation and carcinogens of all kinds. These naked mole rats are incredibly reluctant to get cancer. And that is not the half of it:

In 2004, Buffenstein and her students tried one of these shortcuts. They placed some mole rats in a gamma chamber and blasted their pale, pink bodies with ionizing rays. The animals were unimpressed. When I visited Buffenstein’s lab this past July, many were still alive, skittering through the plastic tubes of their basement habitat at the Barshop Institute for Longevity and Aging Studies.

Four years later, Buffenstein…infected cells from a naked mole rat with a virus designed to corrupt their nuclei with the cancer-causing genes SV40 TAg and Ras. Then she slipped those cells into a live mouse, under the skin behind its ear. If you do the same using infected material from a mouse or a rat, or even a cow or a human, the transplant quickly grows into a deadly tumor, invading nearby fat and muscle tissue. But when Buffenstein and her colleagues used cells from a naked mole-rat, nothing happened.

…Earlier this year, one of Buffenstein’s graduate students tried smearing the skin of half a dozen naked mole rats with a pair of vicious carcinogens: A synthetic compound called DMBA and an inflammatory agent known as TPA. When the same toxic pairing was applied to regular Black-6 lab mice as an experimental control, a cluster of tumors popped up within weeks. Every single mouse had cancer, and every single mouse died. The naked mole rats went on skittering through their tubes.

…Her latest assault involves pouring carcinogens down the mole rats’ throats in a last-ditch effort to induce liver or mammary cancer. But that may not work, either. For years, Buffenstein’s laboratory Rasputins have been irradiated, poisoned, and heated up; their cells dosed with every imaginable pollutant—chemotherapies, oxidative stressors, and heavy metals—with little or no effect. “You name it,” the professor says, “we tried all the kinds of toxins that are out there, and the naked mole rat seems to be very resilient and resistant.”

…The very thing that makes naked mole rats so interesting to Buffenstein—an astonishing vitality that lasts for decades—only makes her research more difficult. “You’re caught between a rock and a hard place, because they live so long that your grandchildren have to finish the studies you start.” Still, slow science may have rich rewards, and the decisions we make today—on whether to invest in new model organisms or build out the ones we already have—are sure to have profound effects on the (human) generations to come. _Slate

The above Slate article by Daniel Engber is an excellent example of good science writing. We learn about the things that make the naked mole rat intriguing as an object of study, then we learn why the biomedical funding establishment is so biased against funding studies using naked mole rats. The life of science is full of such conflicts, which can drive scientists out of the lab entirely if they cannot learn to deal with the frustrating politics and grant grubbing.

No human would want to trade places with a naked mole rat, even if it meant living 10 times longer — and in better health — than the average human. But we might want some of the naked rats resistance to cancer and degenerative change.

Human gerontologists are not trying to discover the path to immortality. They are not even trying to give humans the relative advantage in life span that the naked mole rat has over other rodents. What human scientists are trying to achieve is fairly modest — they want to find a way to delay the signs of aging for roughly seven years beyond the average:

THE TARGET What we have in mind is not the unrealistic pursuit of dramatic increases in life expectancy, let alone the kind of biological immortality best left to science fiction novels.20 Rather, we envision a goal that is realistically achievable: a modest deceleration in the rate of aging sufficient to delay all aging-related diseases and disorders by about seven years.21 This target was chosen because the risk of death and most other negative attributes of aging tends to rise exponentially throughout the adult lifespan with a doubling time of approximately seven years.22 Such a delay would yield health and longevity benefits greater than what would be achieved with the elimination of cancer or heart disease.23 And we believe it can be achieved for generations now alive.

If we succeed in slowing aging by seven years, the age-specific risk of death, frailty, and disability will be reduced by approximately half at every age. People who reach the age of 50 in the future would have the health profile and disease risk of today’s 43-year-old; those aged 60 would resemble current 53-year-olds, and so on. Equally important, once achieved, this seven-year delay would yield equal health and longevity benefits for all subsequent generations, much the same way children born in most nations today benefit from the discovery and development of immunizations.

A growing chorus of scientists agrees that this objective is scientifically and technologically feasible. How quickly we see success depends in part on the priority and support devoted to the effort. Certainly such a great goal – to win back, on average, seven years of healthy life – requires and deserves significant resources in time, talent and treasury. But with the mammoth investment already committed in caring for the sick as they age, and the pursuit of ever-more expensive treatments and surgical procedures for existing fatal and disabling diseases, the pursuit of the Longevity Dividend would be modest by comparison. In fact, because a healthier, longer-lived population will add significant wealth to the economy, an investment in the Longevity Dividend would likely pay for itself. _”TheScientist“_via_NR

Can we learn anything toward that end, from the naked mole rat? Quite possibly. But we have to be willing to put in the time and expense to learn how to transfer the lessons from that exceptional rodent to the human species.

Al Fin Longevity

Dror Sagi (Stanford; Kim lab) — Engineering a long-lived worm

If aging is an engineering problem, then we should be able to solve the engineering challenges more easily in simple systems.

By introducing genes regulation from a long-lived organism into the genome of a short-lived organism, it should be possible to add pro-longevity functions – in effect “upgrading” the short-lived animal so that it lives longer. Sagi has set out to do just that, by transferring genes from the long-lived zebrafish (4-year lifespan) to the short-lived work (4-week lifespan).

The first gene he described was the UCP2 gene, the subject of an earlier talk. Expressing fish UCP2 in the worm lowers overall ATP, and extends worm lifespan. As an important control, expressing an additional copy of the worm UCP2 under the same promoter control does not extend life.

Likewise, fish lysozyme results in lower daf-16 activity, and also extends lifespan. The fish enzyme appears to act by decreasing the pathogenesis from E. coli, an unnatural food source for the worm that causes health problems in late life.

Overall, Sagi characterized 5 well-characterized longevity pathways, testing 16 genes and getting 7 hits.

The next obvious question: Can “upgrade” genes be combined to further increase lifespan? Indeed they can: several pairwise combinations of genes combined to extend lifespan longer than either single gene alone. At some point it worked a little to well: the lifespan of the worms started getting long enough that the survival curves became unwieldy.

• Staying with the worm…

Monika Suchanek (UCSF; Kenyon lab) — The germline and somatic reproductive tissues influence C. elegans

Classically, it had been assumed that there is a tradeoff between lifespan and the number of progeny produced over the lifespan. We now know that this isn’t necessarily true; there are several examples of long-lived mutants that have a normal number of progeny (though the kinetics may be slower, which poses an issue with respect to fitness: if I live twice as long as you and have the same number of progeny but half as quickly, I will probably lose the evolutionary race).

Suchanek began by reviewing old data (like, from when I was a rotation student in the Kenyon lab: old) demonstrating that removal of the germ cells results in lifespan extension, but that this longevity enhancement requires the presence of the somatic gonad. This loss of the germline causes nuclear accumulation of the DAF-16/FOXO protein in the intestine. It is clear from several diverse pieces of data that the somatic gonad and germ line exert their effects on longevity somewhat independently.

Two other genes, daf-9 and daf-12 are required for the extended longevity of germline-deficient worms. DAF-9 is an enzyme that makes dafachronic acid, the ligand of a receptor encoded by DAF-12. Addition of dafachronic acid has no effect on lifespan of germ-cell-deficient, somatic-cell-competent cells, but it does extend the lifespan of animals that lack both germ cells and the somatic gonad.

How does the intestine know that the germ line is gone? To answer this question, Suchanek screened a “signaling sublibrary” of 1304 genes, and got 115 unique hits including several components of the Wnt pathway. Two components, mom-2 and wrm-1 (ß-catenin), are required for nuclear accumulation of DAF-16/FOXO and for the extended lifespan of germline-deficient worms. Suchanek favors a model in which germ line cells emit Wnt inhibitors.

• Finishing on a strong note…

Monique Stanfel (Buck Institute; Kennedy lab) — Ribosome Function and Aging

The Kennedy lab is interested in identifying longevity/aging genes that are conserved in yeast and worm, and then testing these in the mouse.

In both yeast and worm, deletion/knockdown of many ribosomal proteins (RPs) can extend lifespan. In yeast, most if not all of the RPs with a role in lifespan are components of the large subunit (60S). In worm, knockdowns of both small and large subunit components can increase lifespan. Three of the genes conserved between worm and yeast can be knocked down in mice.

In order to characterize translation in mouse mutants, Stanfel ran polysome gradients on liver tissue. She analyzed the fractions in two ways, looking at both ribosome-associated RNAs and at the ribosome-associated proteins.

Surprisingly, the Rpl22 gene can be knocked out and has very little effect on global translation in the mouse liver. This may be because a homologous gene, Rpl22L (“-like”) is compensating for the loss of the major species.

Knockout of another gene, Rpl29, has a larger effect on global translation, decreasing the levels of 80S ribosomes. When fed a high-fat diet, Rpl29 knockouts were protected against weight gain, and their blood glucose also remained low; furthermore, the animals were leaner than wildtype. They also resist developing cardiac hypertrophy in another assay – thus, they meet all the preliminary criteria for the time and resource investment of a lifespan study.

Oncogenes are damaged versions of normal genes (‘proto-oncogenes’) that control cell growth and differentiation. It is important to realize that a proto-oncogene is a normal gene; it is only through pathological processes that it becomes an oncogene. Cancer is a multistep process in which multiple genetic alterations must occur, usually over many years. Thus, only after a long span of time will cell differentiation, division, and growth be changed. In human cancers, inherited mutations are relatively rare. (more…)

Research indicates that anxiety symptoms are more prevalent in elderly people than in any other age group, occurring at about twice the rate of younger adults. The types of anxiety disorders most common among the older population include generalized anxiety, mixed anxious-depressive syndrome symptoms, and phobias (often characterized by exaggerations of rational concerns). More rare are late-life onset of obsessive compulsive disorders (OCD) and panic disorders. (more…)

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The proportion of elderly at any age without any chronic conditions is small, and disease can trigger a cascade of events resulting in functional deficits and disability. An increase in the number of activities with which an elder has difficulty increases linearly with comorbidity, that is, coexistent medical conditions that further complicate not only the genesis of a functional deficit but also its treatment. For example, rehabilitation for a stroke for an individual who also has painful, degenerative changes in the foot and a low tolerance for stressful activity secondary to angina with exertion would present a particular rehabilitation challenge. Yet, this example encapsulates geriatric rehabilitation specialist’s emphasis on care and function, not cure and disease. (more…)

Over the past 60 years, many documents, including the 1948 Universal Declaration of Human Rights, have addressed the rights of all persons. But it was not until the Declaration on Social Progress and Development in 1969 that the human rights of the elderly were specifically mentioned in an international rights document (Office of the United Nations High Commissioner for Human Rights). The United Nations adopted the first International Plan of Action on Ageing in 1987 and the General Assembly of the United Nations adopted the Principles for Older Persons in 1991. (more…)