Aging-associated diseases
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An aging-associated disease (commonly termed age-related disease, ARD) is a
disease A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
that is most often seen with increasing frequency with increasing senescence. They are essentially complications of senescence, distinguished from the aging process itself because all adult animals age ( with rare exceptions) but not all adult animals experience all age-associated diseases. The term does not refer to age-specific diseases, such as the childhood diseases
chicken pox Chickenpox, also known as varicella, is a highly contagious disease caused by the initial infection with varicella zoster virus (VZV). The disease results in a characteristic skin rash that forms small, itchy blisters, which eventually scab ...
and measles, only diseases of the elderly. They are also not
accelerated aging disease Progeroid syndromes (PS) are a group of rare genetic disorders that mimic physiological aging, making affected individuals appear to be older than they are. The term ''progeroid syndrome'' does not necessarily imply progeria (Hutchinson–Gilf ...
s, all of which are
genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
s. Examples of aging-associated diseases are
atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no s ...
and cardiovascular disease,
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
, arthritis,
cataracts A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry or double vision, halos around light, trouble w ...
, osteoporosis, type 2 diabetes, hypertension and Alzheimer's disease. The incidence of all of these diseases increases
exponentially Exponential may refer to any of several mathematical topics related to exponentiation, including: *Exponential function, also: **Matrix exponential, the matrix analogue to the above *Exponential decay, decrease at a rate proportional to value *Expo ...
with age. Of the roughly 150,000 people who die each day across the globe, about two thirds—100,000 per day—die of age-related causes. In industrialized nations, the proportion is higher, reaching 90%.


Patterns of differences

By age 3, about 30% of rats have had cancer, whereas by age 85 about 30% of humans have had cancer. Humans,
dog The dog (''Canis familiaris'' or ''Canis lupus familiaris'') is a domesticated descendant of the wolf. Also called the domestic dog, it is derived from the extinct Pleistocene wolf, and the modern wolf is the dog's nearest living relative. Do ...
s and rabbits get Alzheimer's disease, but
rodent Rodents (from Latin , 'to gnaw') are mammals of the order Rodentia (), which are characterized by a single pair of continuously growing incisors in each of the upper and lower jaws. About 40% of all mammal species are rodents. They are n ...
s do not. Elderly rodents typically die of cancer or kidney disease, but not of cardiovascular disease. In humans, the relative incidence of cancer increases exponentially with age for most cancers, but levels off or may even decline by age 60–75 (although colon/
rectal The rectum is the final straight portion of the large intestine in humans and some other mammals, and the gut in others. The adult human rectum is about long, and begins at the rectosigmoid junction (the end of the sigmoid colon) at the le ...
cancer continues to increase). People with the so-called segmental progerias are vulnerable to different sets of diseases. Those with
Werner's syndrome Werner syndrome (WS) or Werner's syndrome, also known as "adult progeria",James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Dermatology''. (10th ed.). Saunders. . is a rare, autosomal recessive disorder ...
experience osteoporosis, cataracts, and, cardiovascular disease, but not neurodegeneration or Alzheimer's disease; those with
Down syndrome Down syndrome or Down's syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is usually associated with physical growth delays, mild to moderate intellectual dis ...
have type 2 diabetes and Alzheimer's disease, but not high blood pressure, osteoporosis or cataracts. In
Bloom syndrome Bloom syndrome (often abbreviated as BS in literature) is a rare autosomal recessive genetic disorder characterized by short stature, predisposition to the development of cancer, and genomic instability. BS is caused by mutations in the '' BLM'' ge ...
, those affected most often die of cancer.


Research

Aging (senescence) increases vulnerability to age-associated diseases, whereas
genetics Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar wor ...
determines vulnerability or resistance between species and individuals within species. Some age-related changes (like graying hair) are said to be unrelated to an increase in mortality. But some
biogerontologist Biogerontology is the sub-field of gerontology concerned with the biological aging process, its evolutionary origins, and potential means to intervene in the process. The term "biogerontology" was coined by S. Rattan, and came in regular use wit ...
s believe that the same underlying changes that cause graying hair also increase mortality in other organ systems and that understanding the incidence of age-associated disease will advance knowledge of the
biology Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single, coherent field. For instance, all organisms are made up of cells that process hereditary i ...
of senescence just as knowledge of
childhood disease The term childhood disease refers to disease that is contracted or becomes symptomatic before the age of 18 or 21 years old. Many of these diseases can also be contracted by adults. Some childhood diseases include: Diseases from three years t ...
s advanced knowledge of
human development Human development may refer to: * Development of the human body * Developmental psychology * Human development (economics) * Human Development Index, an index used to rank countries by level of human development * Human evolution Human evoluti ...
. Strategies for engineered negligible senescence (SENS) is an emerging research strategy that aims to repair "root causes" for age-related illness and degeneration, as well as develop medical procedures to periodically repair all such damage in the human body, thereby maintaining a youth-like state indefinitely.The SENS Platform: An Engineering Approach to Curing Aging
. Methuselah Foundation. Retrieved on June 28, 2008.
The SENS programme has identified seven types of aging-related damage, and feasible solutions have been outlined for each. Some critics argue that the SENS agenda is optimistic at best, and that the aging process is too complex and little-understood for SENS to be scientific or implementable in the foreseeable future. It has been proposed that age-related diseases are mediated by vicious cycles. On the basis of extensive research,
DNA damage DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA d ...
has emerged a major culprit in
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
and numerous other diseases related to ageing. DNA damage can initiate the development of cancer or other aging related diseases depending on several factors. These include the type, amount, and location of the DNA damage in the body, the type of cell experiencing the damage and its stage in the
cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and sub ...
, and the specific
DNA repair DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA da ...
processes available to react to the damage. A paper published on 29 March 2022 by a group of scientists at Insilico Medicine,
University of Chicago The University of Chicago (UChicago, Chicago, U of C, or UChi) is a private university, private research university in Chicago, Illinois. Its main campus is located in Chicago's Hyde Park, Chicago, Hyde Park neighborhood. The University of Chic ...
, George Mason University, and
University of Liverpool , mottoeng = These days of peace foster learning , established = 1881 – University College Liverpool1884 – affiliated to the federal Victoria Universityhttp://www.legislation.gov.uk/ukla/2004/4 University of Manchester Act 200 ...
demonstrated that there might be several alternative senolytic targets and pathways that can be targeted with small molecules drugs. They use
artificial intelligence Artificial intelligence (AI) is intelligence—perceiving, synthesizing, and inferring information—demonstrated by machines, as opposed to intelligence displayed by animals and humans. Example tasks in which this is done include speech r ...
models to yield a list of dual-purpose targets implicated in aging and age-associated diseases. It may impact multiple age-associated diseases and retard aging for extending
healthspan Life expectancy is a statistical measure of the average time an organism is expected to live, based on the year of its birth, current age, and other demographic factors like sex. The most commonly used measure is life expectancy at birth ...
.


Types


Macular degeneration

Age-related
macular degeneration Macular degeneration, also known as age-related macular degeneration (AMD or ARMD), is a medical condition which may result in blurred or no vision in the center of the visual field. Early on there are often no symptoms. Over time, however, som ...
(AMD) is a disease that affects the eyes and can lead to vision loss through break down of the central part of the retina called the macula. Degeneration can occur in one eye or both and can be classified as either wet (neovascular) or dry (atrophic). Wet AMD commonly is caused by blood vessels near the retina that lead to swelling of the macula. The cause of dry AMD is less clear, but it is thought to be partly caused by breakdown of light-sensitive cells and tissue surrounding the macula. A major risk factor for AMD is age over the age of 60.


Alzheimer's

Alzheimer's disease is classified as a "protein misfolding" disease. Aging causes mutations in protein folding, and as a result causes deposits of abnormal modified proteins accumulate in specific areas of the brain. In Alzheimer's,deposits of Beta-amyloid and hyperphosphorylated tau protein form extracellular plaques and extracellular tangles. These deposits are shown to be neurotoxic and cause cognitive impairment due to their initiation of destructive biochemical pathways.


Atherosclerosis

Atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no s ...
is categorized as an aging disease and is brought about by vascular remodeling, the accumulation of plaque, and the loss of arterial elasticity. Over time, these processes can stiffen the vasculature. For these reasons, older age is listed as a major risk factor for atherosclerosis. Specifically, the risk of atherosclerosis increases for men above 45 years of age and women above 55 years of age.


Benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) is a noncancerous enlargement of the prostate gland due to increased growth. An enlarged prostate can result in incomplete or complete blockage of the bladder and interferes with a man's ability to urinate properly. Symptoms include
overactive bladder Overactive bladder (OAB) is a condition where there is a frequent feeling of needing to urinate to a degree that it negatively affects a person's life. The frequent need to urinate may occur during the day, at night, or both. If there is loss ...
, decreased stream of urine, hesitancy urinating, and incomplete emptying of the bladder. By age 40, 10% of men will have signs of BPH and by age 60, this percentage increases by 5 fold. Men over the age of 80 have over a 90% chance of developing BPH and almost 80% of men will develop BPH in their lifetime.


Cancer

Although it is possible for
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
to strike at any age, most patients with invasive cancer are over 65, and the most significant
risk factor In epidemiology, a risk factor or determinant is a variable associated with an increased risk of disease or infection. Due to a lack of harmonization across disciplines, determinant, in its more widely accepted scientific meaning, is often ...
for developing cancer is age. According to cancer researcher Robert A. Weinberg, "If we lived long enough, sooner or later we all would get cancer." Some of the association between aging and cancer is attributed to
immunosenescence Immunosenescence is the gradual deterioration of the immune system, brought on by natural age advancement. A 2020 review concluded that the adaptive immune system is affected more than the innate immune system. Immunosenescence involves both the ...
, errors accumulated in DNA over a lifetime and age-related changes in the
endocrine system The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neu ...
. Aging's effect on cancer is complicated by factors such as DNA damage and inflammation promoting it and factors such as vascular aging and endocrine changes inhibiting it.


Parkinson's

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
, or simply Parkinson's, is a long-term degenerative disorder of the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
that mainly affects the
motor system The motor system is the set of central and peripheral structures in the nervous system that support motor functions, i.e. movement. Peripheral structures may include skeletal muscles and neural connections with muscle tissues. Central structur ...
. The disease has many complications, including
Dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...
, depression, anxiety. Parkinson's disease typically occurs in people over the age of 60, of whom about one percent are affected. The prevalence of
Parkinson's disease dementia Parkinson's disease dementia (PDD) is dementia that is associated with Parkinson's disease (PD). Together with dementia with Lewy bodies (DLB), it is one of the Lewy body dementias characterized by abnormal deposits of Lewy bodies in the brain. ...
also increases with age, and to a lesser degree, duration of the disease. Exercise in middle age may reduce the risk of PD later in life.


Stroke

Stroke was the second most frequent cause of death worldwide in 2011, accounting for 6.2 million deaths (~11% of the total). Stroke could occur at any age, including in childhood, the risk of stroke increases exponentially from 30 years of age, and the cause varies by age. Advanced age is one of the most significant stroke risk factors. 95% of strokes occur in people age 45 and older, and two-thirds of strokes occur in those over the age of 65. A person's risk of dying if he or she does have a stroke also increases with age.


See also

*
Accelerated aging disease Progeroid syndromes (PS) are a group of rare genetic disorders that mimic physiological aging, making affected individuals appear to be older than they are. The term ''progeroid syndrome'' does not necessarily imply progeria (Hutchinson–Gilf ...
* Alliance for Aging Research * Gerontology * Senescence


References


External links


Segmental Progeria
{{Longevity Geriatrics Senescence