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Senescence or biological aging is the gradual deterioration of functional characteristics in living organisms. Whole organism senescence involves an increase in death rates or a decrease in fecundity with increasing age,at least in the later part of an organism's life cycle. However,the resulting effects of senescence can be delayed. The 1934 discovery that calorie restriction can extend lifespans by 50% in rats,the existence of species having negligible senescence,and the existence of potentially immortal organisms such as members of the genus Hydra have motivated research into delaying senescence and thus age-related diseases. Rare human mutations can cause accelerated aging diseases.
Maximum life span is a measure of the maximum amount of time one or more members of a population have been observed to survive between birth and death. The term can also denote an estimate of the maximum amount of time that a member of a given species could survive between birth and death,provided circumstances that are optimal to that member's longevity.
The free radical theory of aging states that organisms age because cells accumulate free radical damage over time. A free radical is any atom or molecule that has a single unpaired electron in an outer shell. While a few free radicals such as melanin are not chemically reactive,most biologically relevant free radicals are highly reactive. For most biological structures,free radical damage is closely associated with oxidative damage. Antioxidants are reducing agents,and limit oxidative damage to biological structures by passivating them from free radicals.
In chemistry and biology,reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (O2),water,and hydrogen peroxide. Some prominent ROS are hydroperoxide (O2H),superoxide (O2-),hydroxyl radical (OH.),and singlet oxygen. ROS are pervasive because they are readily produced from O2,which is abundant. ROS are important in many ways,both beneficial and otherwise. ROS function as signals,that turn on and off biological functions. They are intermediates in the redox behavior of O2,which is central to fuel cells. ROS are central to the photodegradation of organic pollutants in the atmosphere. Most often however,ROS are discussed in a biological context,ranging from their effects on aging and their role in causing dangerous genetic mutations.
Calorie restriction mimetics (CRM),also known as energy restriction mimetics,are a hypothetical class of dietary supplements or drug candidates that would,in principle,mimic the substantial anti-aging effects that calorie restriction (CR) has on many laboratory animals and humans. CR is defined as a reduction in calorie intake of 20% to 50% without incurring malnutrition or a reduction in essential nutrients. An effective CRM would alter the key metabolic pathways involved in the effects of CR itself,leading to preserved youthful health and longer lifespan without the need to reduce food intake. The term was coined by Lane,Ingram,Roth of the National Institute on Aging in a seminal 1998 paper in the Journal of Anti-Aging Medicine,the forerunner of Rejuvenation Research. A number of genes and pathways have been shown to be involved with the actions of CR in model organisms and these represent attractive targets for drug discovery and for developing CRM. However,no effective CRM have been identified to date.
The mammalian target of rapamycin (mTOR),also referred to as the mechanistic target of rapamycin,and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1),is a kinase that in humans is encoded by the MTOR gene. mTOR is a member of the phosphatidylinositol 3-kinase-related kinase family of protein kinases.
A neurodegenerative disease is caused by the progressive loss of neurons,in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis,multiple sclerosis,Parkinson's disease,Alzheimer's disease,Huntington's disease,multiple system atrophy,tauopathies,and prion diseases. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry,ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons,these diseases are considered to be incurable;however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the subcellular level,including atypical protein assemblies and induced cell death. These similarities suggest that therapeutic advances against one neurodegenerative disease might ameliorate other diseases as well.
RAGE,also called AGER,is a 35 kilodalton transmembrane receptor of the immunoglobulin super family which was first characterized in 1992 by Neeper et al. Its name comes from its ability to bind advanced glycation endproducts (AGE),which include chiefly glycoproteins,the glycans of which have been modified non-enzymatically through the Maillard reaction. In view of its inflammatory function in innate immunity and its ability to detect a class of ligands through a common structural motif,RAGE is often referred to as a pattern recognition receptor. RAGE also has at least one other agonistic ligand:high mobility group protein B1 (HMGB1). HMGB1 is an intracellular DNA-binding protein important in chromatin remodeling which can be released by necrotic cells passively,and by active secretion from macrophages,natural killer cells,and dendritic cells.
Following is a list of topics related to life extension:
8-Oxoguanine glycosylase,also known as OGG1,is a DNA glycosylase enzyme that,in humans,is encoded by the OGG1 gene. It is involved in base excision repair. It is found in bacterial,archaeal and eukaryotic species.
Superoxide dismutase [Cu-Zn] also known as superoxide dismutase 1 or hSod1 is an enzyme that in humans is encoded by the SOD1 gene,located on chromosome 21. SOD1 is one of three human superoxide dismutases. It is implicated in apoptosis,familial amyotrophic lateral sclerosis and Parkinson's disease.
Superoxide dismutase 2,mitochondrial (SOD2),also known as manganese-dependent superoxide dismutase (MnSOD),is an enzyme which in humans is encoded by the SOD2 gene on chromosome 6. A related pseudogene has been identified on chromosome 1. Alternative splicing of this gene results in multiple transcript variants. This gene is a member of the iron/manganese superoxide dismutase family. It encodes a mitochondrial protein that forms a homotetramer and binds one manganese ion per subunit. This protein binds to the superoxide byproducts of oxidative phosphorylation and converts them to hydrogen peroxide and diatomic oxygen. Mutations in this gene have been associated with idiopathic cardiomyopathy (IDC),premature aging,sporadic motor neuron disease,and cancer.
Poly [ADP-ribose] polymerase 1 (PARP-1) also known as NAD+ ADP-ribosyltransferase 1 or poly[ADP-ribose] synthase 1 is an enzyme that in humans is encoded by the PARP1 gene. It is the most abundant of the PARP family of enzymes,accounting for 90% of the NAD+ used by the family. PARP1 is mostly present in cell nucleus,but cytosolic fraction of this protein was also reported.
Cellular senescence is a phenomenon characterized by the cessation of cell division. In their experiments during the early 1960s,Leonard Hayflick and Paul Moorhead found that normal human fetal fibroblasts in culture reach a maximum of approximately 50 cell population doublings before becoming senescent. This process is known as "replicative senescence",or the Hayflick limit. Hayflick's discovery of mortal cells paved the path for the discovery and understanding of cellular aging molecular pathways. Cellular senescence can be initiated by a wide variety of stress inducing factors. These stress factors include both environmental and internal damaging events,abnormal cellular growth,oxidative stress,autophagy factors,among many other things.
The DNA damage theory of aging proposes that aging is a consequence of unrepaired accumulation of naturally occurring DNA damage. Damage in this context is a DNA alteration that has an abnormal structure. Although both mitochondrial and nuclear DNA damage can contribute to aging,nuclear DNA is the main subject of this analysis. Nuclear DNA damage can contribute to aging either indirectly or directly.
Colostrinin is a naturally occurring mixture of proline-rich polypeptides derived from colostrum.
Genetics of aging is generally concerned with life extension associated with genetic alterations,rather than with accelerated aging diseases leading to reduction in lifespan.
The mitochondrial theory of ageing has two varieties:free radical and non-free radical. The first is one of the variants of the free radical theory of ageing. It was formulated by J. Miquel and colleagues in 1980 and was developed in the works of Linnane and coworkers (1989). The second was proposed by A. N. Lobachev in 1978.
Senescence-associated secretory phenotype (SASP) is a phenotype associated with senescent cells wherein those cells secrete high levels of inflammatory cytokines,immune modulators,growth factors,and proteases. SASP may also consist of exosomes and ectosomes containing enzymes,microRNA,DNA fragments,chemokines,and other bioactive factors. Soluble urokinase plasminogen activator surface receptor is part of SASP,and has been used to identify senescent cells for senolytic therapy. Initially,SASP is immunosuppressive and profibrotic,but progresses to become proinflammatory and fibrolytic. SASP is the primary cause of the detrimental effects of senescent cells.
Aging is characterized by a progressive loss of physiological integrity,leading to impaired function and increased vulnerability to death. The hallmarks of aging are the types of biochemical changes that occur in all organisms that experience biological aging and lead to a progressive loss of physiological integrity,impaired function and,eventually,death. They were first listed in a landmark paper in 2013 to conceptualize the essence of biological aging and its underlying mechanisms.
References
- 1 2 3 4 "Department of Nutritional Sciences - University of Oklahoma Health Sciences".
- ↑ "Arlan Richardson - Google Scholar".
- ↑ "Effect of age and dietary restriction on the expression of alpha 2u-globulin".
- ↑ "Expression of heat shock protein 70 is altered by age and diet at the level of transcription".
- ↑ "Does oxidative damage to DNA increase with age?".
- ↑ "The role of oxidative damage and stress in aging".
- ↑ "Increased oxidative damage is correlated to altered mitochondrial function in heterozygous manganese superoxide dismutase knockout mice".
- ↑ "Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging".
- ↑ "Trends in oxidative aging theories".
- ↑ "Is the Oxidative Stress Theory of Aging Dead?".
- ↑ "Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's disease".
- ↑ "Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments".
- ↑ "Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity".
- ↑ "Necroptosis increases with age and is reduced by dietary restriction".
- ↑ "Necroptosis contributes to chronic inflammation and fibrosis in aging liver".
- ↑ "Senolytic treatment reduces cell senescence and necroptosis in Sod1 knockout mice that is associated with reduced inflammation and hepatocellular carcinoma".
- ↑ "Award Info - Gerontological Society of America".
- ↑ "The Irving S. Wright Award of Distinction".
- ↑ "Lord Cohen of Birkenhead Medal".
