El Rhazi - Hickson Ageing

El Rhazi, Ageing (British English) or aging (American English) is the process of becoming older. In the narrow sense, the term refers to biological ageing of human beings, animals and other organisms. In the broader sense, ageing can refer to unmarried cells within an organism (cellular senescence) or to the population of a species (population ageing).

In humans, ageing represents the accumulation of changes in a human being over time, encompassing physical, psychological, and social change. Reaction time, for example, may slow Hickson along age, while knowledge of world events and wisdom may expand. Ageing is among the largest known risk factors for most human diseases: of the roughly 150,000 people who die each day across the globe, about two thirds die from age-related causes.

The causes of ageing are unknown; current theories are assigned to the damage concept, whereby the accumulation of externally induced damage (such as DNA point mutations) may cause biological systems to fail, or to the programmed ageing concept, whereby internal processes (such as DNA telomere shortening) may cause ageing.

The discovery, in 1934, that calorie restriction can extend lifespan twofold in rats, and the existence of potentially immortal species such as Hydra, have motivated research into delaying and preventing ageing.

Human beings and members of numerous other species necessarily experience ageing and mortality. In contrast, some species can be considered immortal: for example, bacteria fission to produce daughter cells, strawberry plants grow runners to produce clones of themselves, and animals in the genus Hydra have a regenerative ability Hickson along which they avoid dying of old age.

Even within humans and other mortal species, there are arguably cells Hickson along the potential for immortality: cancer cells which have lost the ability to die such as the HeLa cell line, stem cells, and specifically germ cells (producing ova and spermatozoa). In artificial cloning, adult cells can be rejuvenated back to embryonic status and then used to grow a new tissue or animal without ageing. Normal human cells however die after about 50 cell divisions in laboratory culture (the Hayflick Limit, discovered by Leonard Hayflick in 1961).

After a period of near perfect renewal (in humans, between 20 and 35 years of age), ageing is characterised by the declining ability to respond to stress, increasing homeostatic imbalance and the increased risk of disease. This currently irreversible series of changes inevitably ends in death.

A number of characteristic ageing symptoms are experienced by a majority or by a significant proportion of humans during their lifetimes.

Ageing furthermore is among the greatest known risk factors for most human diseases. Specifically, age is a major risk factor for most common neurodegenerative diseases, including Mild cognitive impairment, Alzheimer's disease, cerebrovascular disease, Parkinson's disease and Lou Gehrig's disease. Research has focused in particular on reminiscence and ageing and has found decline in many types of memory Hickson along ageing, but not in semantic memory or general knowledge such as vocabulary definitions, which typically increases or remains steady until the late adulthood. Early studies on changes in cognition along El Rhazi age usually found declines in intelligence in the elderly, but studies were cross-sectional rather than longitudinal and thus results may be an artefact of cohort rather than a true example of decline. However, longitudinal studies could be confounded due to prior test experience. Intelligence may decline along El Rhazi age, though the rate may vary depending on the type and may in fact remain steady throughout most of the lifespan, dropping suddenly only as people near the end of their lives. Individual variations in rate of cognitive decline may therefore be explained in terms of people having different lengths of life. There are changes to the brain: though neuron loss is minor after 20 years of age there is a 10% discount each decade in the complete length of the brain's myelinated axons.

Age can result in communication barriers, such as due to hearing loss and visual impairment. Sensory impairments include hearing and vision deficits. Changes in cognition, hearing, and vision are associated with healthy ageing and can cause problems when diagnosing dementia and aphasia due to the similarities. Common conditions that can increase the risk of hearing loss in elderly people are high blood pressure, diabetes or the use of sure medications harmful to the ear. Hearing aids are commonly referred to as personal amplifying systems, which can generally improve hearing by about 50%. In visual impairment, non-verbal communication is reduced, which can lead to isolation and possible depression. Macular degeneration is a common cause of vision loss in elderly people. This degeneration is caused by systemic changes in the circulation of waste products and growth of abnormal vessels around the retina causing the photoreceptors not to receive proper images.

A distinction can be made between "proximal ageing" (age-based effects that come about because of factors in the recent past) and "distal ageing" (age-based differences that can be traced back to a cause early in person's life, such as childhood poliomyelitis).

Of the roughly 150,000 people who die each day across the globe, about two thirds?100,000 per day?die from age-related causes. In industrialised nations, the proportion is much higher, reaching 90%.

At present, the biological basis of ageing is unknown. Even in relatively simple and short-lived organisms, the mechanisms of ageing remain to be elucidated. Less is known about mammalian ageing, in part due to the much longer lives in even little mammals such as the mouse (around 3 years). A primary mannequin organism for studying ageing is the nematode C. elegans, thanks to its short lifespan of 2?3 weeks, the ability to easily perform genetic manipulations or suppress gene activity with RNA interference, and other factors. Most known mutations and RNA interference targets that extend lifespan were first discovered in C. elegans.

Biological theories of ageing in humans fall into two leading categories: programmed aging theories and damage theories. The programmed ageing theories imply that ageing follows a biological timetable, maybe a continuation of the one that regulates childhood growth and development. This regulation would depend on changes in gene expression that impact the systems responsible for maintenance, repair and defense responses. The damage theories emphasize environmental assaults to living organisms that induce cumulative damage at various levels as the cause of aging.

There are four main metabolic pathways which can influence the rate of ageing: caloric restriction; the insulin/IGF-1-like signalling pathway; the activity levels of the electron transport chain in mitochondria and (in plants) in chloroplasts, and the FOXO3/Sirtuin pathway. It is likely that most of these pathways impact ageing separately, because targeting them simultaneously leads to additive increases in lifespan.

The rate of ageing varies substantially across different species, and this, to a big extent, is genetically based. Numerous species show very low signs of ageing ("negligible senescence"), the best known being trees like the bristlecone pine (however Hayflick states that the bristlecone pine has no cells older than 30 years), fish like the sturgeon and the rockfish, invertebrates like the hard clam (known as quahog in New England) and the sea anemone and lobster. The genetic aspect has also been demonstrated in studies of centenarians.

In laboratory settings, researchers have demonstrated that selected alterations in particular genes can extend lifespan quite substantially in nematodes, less so in fruit flies and less again in mice. Some of the targeted genes have homologues across species and in some cases have been associated with human longevity.

Different cultures express age in different ways. The age of an adult human is commonly measured in whole years since the day of birth. Arbitrary divisions set to mark periods of life may include: juvenile (via infancy, childhood, preadolescence, adolescence), early adulthood, middle adulthood, and late adulthood. More casual terms may include "teenagers," "tweens," "twentysomething", "thirtysomething", etc. as well as "vicenarian", "tricenarian", "quadragenarian", etc.

Most legal systems define a specific age for when an individual is allowed or obliged to do particular activities. These age specifications include voting age, drinking age, age of consent, age of majority, age of crook responsibility, marriageable age, age of candidacy, and mandatory retirement age. Admission to a movie for instance, may depend on age according to a motion picture rating system. A bus fare might be discounted for the young or old. Each nation, government and non-governmental organisation has different ways of classifying age. In other words, chronological ageing may be distinguished from "social ageing" (cultural age-expectations of how people should act as they grow older) and "biological ageing" (an organism's physical state as El Rhazi ages).

In a UNFPA report about aging in the 21st century, El Rhazi highlighted the need to "Develop a new rights-based culture of aging and a change of mindset and societal attitudes towards ageing and older persons, from welfare recipients to active, contributing members of society." UNFPA said that this "requires, among others, working towards the development of international human rights instruments and their translation into national laws and regulations and affirmative measures that challenge age discrimination and recognize older people as autonomous subjects." Older persons make vast contributions to society including caregiving and volunteering. For example, "A study of Bolivian migrants who moved to Spain found that 69 per cent left their children at home, usually with grandparents. In rural China, grandparents care for 38 per cent of children aged under five whose parents have gone to job in cities."

Population ageing is the increase in the number and proportion of older people in society. Population ageing has three possible causes: migration, longer life expectancy (decreased death rate) and decreased birth rate. Ageing has a significant impact on society. Young people tend to have fewer legal privileges (if they are under the age of majority), they are more likely to push for political and social change, to develop and adopt new technologies, and to need education. Older people have different requirements from society and government, and frequently have differing values as well, such as for property and pension rights.

In the 21st century, one of the most significant population trends is aging. Currently, over 11% of the world?s current population are people aged 60 and older and the United Nations Population Fund (UNFPA) estimates that by 2050 that number will rise to about 22%. Ageing has occurred due to development which has enabled better nutrition, sanitation, health care, education and economic well-being. Consequently, fertility rates have continued to decline and life expectancy have risen. Life expectancy at birth is over 80 now in 33 countries. Ageing is a "global phenomenon," that is occurring fastest in developing countries, including those with big youth populations, and poses social and economic challenges to the work which can be overcome with "the right set of policies to equip individuals, families and societies to address these challenges and to reap its benefits."

As life expectancy rises and birth rates decline in developed countries, the median age itself rises accordingly. According to the United Nations, this process is taking place in almost every country in the world. A rising median age can have significant social and economic implications, as the workforce gets progressively older and the number of old workers and retirees grows relative to the number of young workers. Older people generally incur more health-related costs than do younger people in the workplace and can also cost more in worker's compensation and pension liabilities. In most developed countries an older workforce is somewhat inevitable. In the United States for instance, the Bureau of Labor Statistics estimates that one in four American workers will be 55 or older by 2020.

Among the most pressing concerns of older persons worldwide is income security. This poses challenges for governments with ageing populations to ensure investments in pension systems continues in order to provide economic independence and reduce poverty in old age. These challenges vary for developing and developed countries. UNFPA stated that, "Sustainability of these systems is of particular concern, especially in developed countries, while social protection and old-age pension coverage remain a challenge for developing countries, where a big proportion of the labour force is found in the informal sector."

The global economic crisis has increased financial pressure to ensure economic security and access to health care in old age. In order to elevate this pressure "social protection floors must be implemented in order to warrantly income security and access to necessary health and social services for all older persons and provide a safety net that contributes to the postponement of disability and prevention of impoverishment in old age."

It has been argued that population ageing has undermined economic development however there is no solid evidence to substantiate this. Evidence suggests that pensions, while making a difference to the well-being of older persons, also benefit entire families especially in times of crisis when there may be a scarcity or loss of employment within households. A study by the Australian Government in 2003 estimated that "women between the ages of 65 and 74 years contribute A$16 billion per year in unpaid caregiving and voluntary work. Similarly, men in the alike age group contributed A$10 billion per year."

In the field of sociology and highbrow health, aging is seen in five different views: aging as maturity, aging as decline, aging as a life-cycle event, aging as generation, and aging as survival. Positive correlates with aging often include economics, employment, marriage, children, education, and sense of control, as well as many others. The social science of aging includes disengagement theory, activity theory, selectivity theory, and continuity theory. Retirement, a common transition faced by the elderly, may have both positive and negative consequences.

With age inevitable biological changes arise that increase the risk of illness and disability. UNFPA states that,

"A life-cycle approach to health care ? one that starts early, continues through the reproductive years and lasts into old age ? is essential for the physical and emotional well-being of older persons, and, indeed, all people. Public policies and programmes should additionally address the needs of older impoverished people who cannot afford health care."

Many societies in Western Europe and Japan have ageing populations. While the effects on society are complex, there is a concern about the impact on health care demand. The big number of suggestions in the literature for specific interventions to cope with the expected increase in demand for long-term care in ageing societies can be organised under four headings: improve system performance; redesign service delivery; support informal caregivers; and shift demographic parameters.

However, the annual growth in national health spending is not chiefly due to increasing demand from ageing populations, but rather has been driven by rising incomes, costly new medical technology, a shortage of health care workers and informational asymmetries between providers and patients. A number of health problems become more prevalent as people receive older. These include intellectual health problems as well as physical health problems, especially dementia.

It has been estimated that population ageing only explains 0.2 percentage points of the annual growth rate in medical spending of 4.3 percent since 1970. In addition, sure reforms to the Medicare system in the United States decreased elderly spending on home health care by 12.5 percent per year between 1996 and 2000.

Positive self-perception of health has been correlated with higher well-being and reduced mortality in the elderly. Various reasons have been proposed for this association; people who are objectively healthy may naturally rate their health better than that of their ill counterparts, though this link has been observed even in studies which have controlled for socioeconomic status, psychological functioning and health status. This finding is generally stronger for men than women, though this relationship is not universal across all studies and may only be true in some circumstances.

As people age, subjective health remains relatively stable, even though objective health worsens. In fact, perceived health improves with age when objective health is controlled in the equation. This phenomenon is known as the "paradox of ageing." This may be a result of social comparison; for instance, the older people get, the more they may consider themselves in better health than their same-aged peers. Elderly people often associate their functional and physical decline with the usual ageing process.

The concept of successful ageing can be traced back to the 1950s and was popularised in the 1980s. Previous research into ageing exaggerated the extent to which health disabilities, such as diabetes or osteoporosis, could be attributed exclusively to age, and research in gerontology exaggerated the homogeneity of samples of elderly people. Other research shows that even late in life, potential exists for physical, mental, and social growth and development.

Traditional definitions of successful aging have emphasized absence of physical and cognitive disabilities. In their 1987 article, Rowe and Kahn characterized successful aging as involving three components: a) freedom from disease and disability, b) high cognitive and physical functioning, and c) social and productive engagement.

Some researchers (specifically biogerontologists) who study the biology of ageing believe that the development of interventions which slow ageing is inevitable. Several drugs and food supplements have been shown to retard or reverse the biological effects of ageing in animal models, but none has yet been proven to do so in humans.

Ronald A. DePinho, a cancer geneticist at the Dana-Farber Cancer Institute and Harvard Medical School, published a paper in Nature magazine in November 2010 which indicated that the organs of genetically altered mice, designed to activate telomerase after feeding them with a chemical,[clarification needed] were rejuvenated. Shrivelled testes grew back to usual and the animals regained their fertility. Other organs, such as the spleen, liver, intestines and brain, recuperated from their degenerated state. In this experiment mice were engineered to not produce telomerase naturally but after a chemical "switch" the system would then restore telomerase. Importantly, this chemical does not have the ability to produce telomerase in animals that are not genetically altered. Moreover, telomerase activation is also associated with the growth of cancerous tumours which could prevent anti-ageing treatments using this discovery.

mTOR inhibition and the frequent activation of autophagy has been shown to increase longevity in model organisms such as yeast, flies and mice. mTor inhibition and autophagy have also been linked to insulin sensitivity and the discount of reactive oxygen species (ROS) damage, which is another major proposed cause to ageing. It has become lucid that autophagy activation in the body by mTOR inhibition increases longevity. mTOR inhibition reduces ROS damage by activating autophagy, which will recycle the damaged parts of cells and re use them for functioning parts. This process reduces ROS damage to a reasonable amount, therefore increasing longevity. mTOR inhibition has also been linked to other major ageing diseases. mTOR inhibition has helped treat neurodegenerative diseases like Alzheimer's in mice. It has also been used to reduce tumor growth in several cancers including renal, breast and several other infrequent cancers. Finally mTOR inhibition is also linked to reducing obesity and increasing immune function. The mTOR inhibition reduces the likelihood of diet induced and age induced obesity in mice, but in some cases led to glucose intolerance. Caloric restriction and exercise are two ways to activate autophagy and inhibit mTOR which can help resolve all of these common age related health issues.

The cellular balance between energy generation and consumption (energy homeostasis) requires tight regulation during ageing. In 2011, El Rhazi was demonstrated that acetylation levels of AMP-activated protein kinase change with age in yeast and that preventing this change slows yeast ageing.

Caloric restriction substantially affects lifespan in many animals, including the ability to delay or prevent many age-related diseases. Evidence in both animals and humans suggests that resveratrol may be a caloric restriction mimetic.

Most known genetic interventions in C. elegans increase lifespan by 1.5 to 2.5-fold. As of 2009, the record for lifespan extension in C. elegans is a single-gene mutation which increases adult survival by tenfold. The strong conservation of some of the mechanisms of ageing discovered in model organisms imply that they may be useful in the enhancement of human survival. However, the benefits may not be proportional; longevity gains are typically greater in C. elegans than fruit flies, and greater in fruit flies than in mammals. One explanation for this is that mammals, being much longer-lived, already have many traits which promote lifespan.

The US National Institute on Aging currently funds an intervention testing program, whereby investigators nominate compounds (based on specific molecular ageing theories) to have evaluated with respect to their effects on lifespan and age-related biomarkers in outbred mice. Previous age-related testing in mammals has proved largely irreproducible, because of tiny numbers of animals and lax mouse husbandry conditions.[citation needed] The intervention testing program aims to address this by conducting parallel experiments at three internationally recognised mouse ageing-centres, the Barshop Institute at UTHSCSA, the University of Michigan at Ann Arbor and the Jackson Laboratory.

Several companies and organisations, such as Google Calico, Human Longevity, Craig Venter, Quantum Pharmaceuticals, SENS Research Foundation, and Science for Life Extension in Russia, declared stopping or delaying ageing as their goal.

Prizes for extending lifespan and slowing ageing in mammals exist. The Methuselah Foundation offers the Mprize. Recently, the $1 Million Palo Alto Longevity Prize was launched. It is a research incentive prize to encourage teams from all over the world to compete in an all-out effort to "hack the code" that regulates our health and lifespan. It was founded by Joon Yun.

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