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Anti-Aging Gene linked to Appetite Regulation Determines Longevity in Humans and Animals

  • May 2018
DOI:10.28933/IJOAR)
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Ian J Martins at University of Western Australia
Ian J Martins
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Abstract

The process of aging is determined by various genetic and environmental factors. Aging is associated with increased oxidative stress that alters cellular chromatin structure, DNA methylation with histone modifications. These epigenetic alterations lead to nuclear changes associated with mitochondrial apoptosis that is a major defect in the global chronic disease epidemic (1). The variability in longevity between individuals in different communities implicate various nutritional and environmental factors involved in transcriptional dysregulation that lead to cell damage that accumulates with age and contributes to mitophagy, insulin resistance and programmed cell death. The absence or malfunction of a gene (2) necessary for transcriptional regulation of gene expression, DNA repair and telomere maintenance in neurons has become essential with relevance to neurodegeneration that determines aging and lifespan in man and animals.
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Dr Ian Martins, School of Medical
Sciences, Edith Cowan University,
Western Australia 6009, Australia,
Ph: +61863042574,
How to cite this article:
Ian James Martins. Anti-Aging
Gene linked to Appetite Regulation
Determines Longevity in Humans
and AnimalsInternational Journal of
Aging Research, 2018, 1:6.
eSciPub LLC, Houston, TX USA.
Website: http://escipub.com/
Ian James Martins, IJOAR, 2018 1:6
International Journal of Aging Research
(DOI:10.28933/IJOAR)
Editorial Article IJOAR (2018) 1:6
Anti-Aging Gene linked to Appetite Regulation Determines
Longevity in Humans and Animals
The process of aging is determined by various genetic and envi-
ronmental factors. Aging is associated with increased oxidative
stress that alters cellular chromatin structure, DNA methylation
with histone modications. These epigenetic alterations lead to
nuclear changes associated with mitochondrial apoptosis that
is a major defect in the global chronic disease epidemic (1). The
variability in longevity between individuals in different commu-
nities implicate various nutritional and environmental factors in-
volved in transcriptional dysregulation that lead to cell damage
that accumulates with age and contributes to mitophagy, insulin
resistance and programmed cell death. The absence or malfunc-
tion of a gene (2) necessary for transcriptional regulation of gene
expression, DNA repair and telomere maintenance in neurons
has become essential with relevance to neurodegeneration that
determines aging and lifespan.
Key words: longevity; species; appetite; immune system; hu-
man; mitophagy; animals; neurodegneration; Sirtuin 1; nutritional
therapy
Ian James Martins
aCentre of Excellence in Alzheimer’s Disease Research and Care, Sarich Neuroscience Research
Institute, Edith Cowan University, Verdun Street, Nedlands, 6009, Western Australia, Australia;
bSchool of Psychiatry and Clinical Neurosciences, The University of Western Australia, Nedlands,
6009; cMcCusker Alzheimer’s Research Foundation, Hollywood Medical Centre, 85 Monash Ave-
nue, Suite 22, Nedlands, 6009, Australia
EDITORIAL
IJOAR: http://escipub.com/international-journal-of-aging-research/ 1
Ian James Martins, IJOAR, 2018 1:6
IJOAR: http://escipub.com/international-journal-of-aging-research/ 2
Major implementations in lifestylestyle changes
have been conducted and to introduce calorie
restriction that alters cell metabolism by the use
of specific nutrients to improve immunity
connected to longevity (3). Genes that
determine premature lifespan in humans have
been identified and include genes (3,4) such as
breast cancer genes BRCA1 and BRCA2 and
hyperlipidemia genes (the low-density
lipoprotein receptor, apolipoprotein B). Four
candidate genes (3) have been implicated in
longevity such as apolipoprotein E, angiotensin-
converting enzyme, histocompatibility locus
antigen and plasminogen activator inhibitor 1.
These genes have effects on longevity in
animals and humans by effects of calorie
restriction (5) that determine the function of
homeostatic proteins with effects on nutrient
metabolism and immunity. A genome-wide scan
has identified new loci for exceptional longevity
and reveal a genetic overlap between longevity
and age-related diseases and traits that include
coronary artery disease and Alzheimer's disease
(6). In humans and animals (dogs, cats, bears,
horses, elephants, livestock/cattle) lifespan can
vary between 29-86 years and in man depending
on the community human lifespan can reach a
maximum of 104 years with average age (70-80
years). Centenarians have very low levels of
chromosome abnormalities (7) and indicate the
absence of the malfunction in genes associated
with DNA repair and DNA methylation that
prevent mitochondrial apoptosis linked to
various chronic diseases such as diabetes and
neurodegenerative diseases. An anti-aging
gene (8) that determines longevity and lifespan
in various species
(Figure 1) has been identified as Sirtuin 1 (Sirt
1). Sirt 1 is a nicotinamide adenine dinucleotide
(NAD +) dependent class III histone deacetylase
(HDAC) that targets transcription factors
(peroxisome proliferator-activated receptor-
gamma coactivator, p53, pregnane x receptor)
to adapt gene expression to metabolic activity
and as a deacetylase is involved in the
deacetylation of the nuclear receptors critical to
neuron proliferation, insulin resistance and non
alcoholic fatty liver disease (1). Sirt 1 is involved
in telomere maintenance and DNA repair with its
critical involvement chromosome stability and
cell proliferation. Sirt 1 is important to the
regulation of other anti-aging genes such as
klotho, p66shc and Forkhead box protein O1
with relevance to age related diseases (8).
Figure 1. In humans and animals Sirt 1 is the
anti-aging/heat shock gene that is sensitive to
heat/cold stress with relevance to the induction
of mitochondrial apoptosis and autoimmune
disease. Sirt 1 regulates food intake and is the
calorie sensitive gene that determines species
survival linked to diabetes and
neurodegenerative diseases.
Major interests in appetite regulation has
indicated that appetite control is critical to
longevity and lifespan and connected to various
chronic diseases (9). Sirt 1 as a heat shock gene
is important to the immune system in various
species (10) with its repression linked to
autoimmune disease (11). Core body
temperature dysregulation will inactivate Sirt 1
and induce mitochondrial apoptosis with
relevance to autoimmune disease and species
longevity (12). Diet, environment and lifestyle
(stress) changes incriminate Sirt 1 as the
defective gene (Figure 1) involved in aging and
lifespan and associated with neurodegeneration
and chronic disease. In animals food quality (13)
is essential to maintain Sirt 1 expression and
activity with relevance to regulation of core body
temperature and autoimmune disease. The
longevity of lifespan in cattle and livestock will be
determined by the xenobiotic content (10) and
Ian James Martins, IJOAR, 2018 1:6
IJOAR: http://escipub.com/international-journal-of-aging-research/ 3
food end products from bacteria/fungus such as
bacterial lipopolysaccharides and mycotoxins
(14). Animals may be more sensitive to
neurodegeneration and synaptic plasticity with
dietary interventions essential to maintain
neuron and synapse interactions (14). The role
of caffeine and Indian Spices (15,16) in food
products has become of interest and may
determine longevity in man. Furthermore
inactivation of Sirt 1 is associated with
senescence and its role in antimicrobial activity
and mitophagy (17) may be critical for the
survival of animal
Conclusion
In humans the function of the anti-aging gene
Sirt 1 is critical to the maintenance of other
longevity and anti-aging genes involved with
aging and lifespan. Appetite regulation is
connected to Sirt 1 function with mitochondrial
apoptosis and neurodegeneration linked to
various chronic diseases. Food consumption in
the cattle and livestock industry should be
carefully controlled since Sirt 1 and its
dysregulation may be more sensitive to
mitochondrial apoptosis in animals with effects
on neurodegeneration and synaptic plasticity
that determines species longevity.
Acknowledgements
This work was supported by grants from Edith
Cowan University, the McCusker Alzheimer's
Research Foundation and the National Health
and Medical Research Council.
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... Novel genes [36] have been identified that are involved with autoimmune disease [18,19,36, 37] and glucolipotoxicity with irreversible immune complications relevant to NAFLD, diabetes [3] and the pathogenetic loop. The discovery of the anti-aging gene Sirt 1 now has become important to the treatment of diabetes with insulin therapy in Type 1 and Type 2 diabetes connected to Sirt 1 activation in the pancreas with relevance to insulin release [38] with Sirt 1 associated with mitochondrial biogenesis (Figure 1) and cell survival in various tissues [38,39]. The inactivation of Sirt 1 [39] in humans leads to the pathogenetic loop in diabetes and implicates nutritional and environmental factors in the induction of programmed cell death. ...
... The discovery of the anti-aging gene Sirt 1 now has become important to the treatment of diabetes with insulin therapy in Type 1 and Type 2 diabetes connected to Sirt 1 activation in the pancreas with relevance to insulin release [38] with Sirt 1 associated with mitochondrial biogenesis (Figure 1) and cell survival in various tissues [38,39]. The inactivation of Sirt 1 [39] in humans leads to the pathogenetic loop in diabetes and implicates nutritional and environmental factors in the induction of programmed cell death. ...
... Insulin therapy has been used to improve liver function but with NAFLD, high dose insulin therapy may be unsuccessful with liver inflammation [40][41][42] associated with uncontrolled hyperglycemia and mitochondrial apoptosis (Figure 2). Insulin therapy with insulin dose and oral anti-diabetic medications should be re-evaluated to improve hepatocyte mitochondrial biogenesis with relevance to reversal of liver disease connected to hyperglycemia and NAFLD in various Type 1, Type 2 and Type 3 [35,39] diabetics. ...
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Nutritional and environmental epigenetics are involved with the repression of anti-aging genes that are linked to the chronic disease epidemic. Unhealthy diets inactivate the calorie sensitive gene Sirtuin 1 (Sirt 1) involved in epigenetic processes that promote immune system alterations, mitochondrial apoptosis, Non-alcoholic Fatty Liver Disease (NAFLD), diabetes and Nitric Oxide (NO) modification with relevance to core body temperature involved with appetite regulation, glucose homeostasis and hepatic xenobiotic metabolism. The interplay between NO and epigenetics has attracted interest with relevance to autoimmune disease and mitophagy that has become of critical concern to diabetes and the development of MODS. Future research involved with nutritional research and the maintenance of Sirt 1 transcriptional control is critical to the prevention of MODS that is linked to the immune system and insulin resistance. In the developing world bacterial lipopolysaccharides a critical repressor of Sirt 1 is now involved with NAFLD and various organ diseases relevant to tissue accumulation of xenobiotics from various environments with relevance to MODS and the global chronic disease epidemic.
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Regulation of Core Body Temperature and the Immune System Determines Species Longevity
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  • Jun 2017
The anti-aging gene Sirtuin 1 has now major relevance to genetics and the fields of pharmacology, toxicology, neurosci¬ence, immunology, biochemistry and cell/molecular biology. Advances in anti-aging therapy are now essential to prevent mitochondrial apoptosis to promote longevity with the pre¬vention of accelerated ageing. Calorie restriction that main¬tains the anti-aging gens changes the core body temperature and promotes species longevity. Stress and calorie consump¬tion are sensitive to Sirt 1 function with relevance heat shock protein 70 metabolism and mitochondrial biogenesis. Sirt 1 regulation of the circadian rhythm mediates melatonin effects on core body temperature regulation and immune responses. Diet and fat are essential factors that determine species lon¬gevity with relevance to heat shock gene regulation and mi¬tochondrial disease in animals and man. Strenuous exercise to activate the cellular heat shock gene in animals and man should be carefully controlled to prevent magnesium deficien¬cy with relevance to immune disorders and mitophagy.
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Dietary Interventions Reverse Insulin and Synaptic Plasticity Defects Linking to Diabetes and Neurodegenerative Diseases
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  • Apr 2017
In the developing world food and nutrition guidelines with relevance to nutrition and metabolism are required to reduce elevated cholesterol levels with relevance to diabetes, Parkinson’s disease and Alzheimer’s disease. In diabetes and neurodegenerative diseases global non alcoholic fatty liver disease (NAFLD) has become of major concern with the reduced hepatic metabolism of toxic compounds that increase with age to milligrams quantities of bacterial lipopolysaccharides (LPS), mycotoxins and xenobiotics that induce neuron death. The increased brain content of these toxic compounds completely inactivate drug therapy with increased repetitive drug exposure to neurons and synpases. In the global diabetes epidemic diabetes is expected to double by the year 2050 in the developing world and diets that reverse or stabilize mitochondrial apoptosis have become relevant to synaptic plasticity and to prevent neuronal death. These toxic compounds determine the survival of various species with relevance to greater toxicity to neurons and their synapses in diabetes when compared to toxic amyloid beta oligomers and alpha synuclein oligomers in Parkinson’s disease and Alzheimer’s disease .
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Food Quality Induces a Miscible Disease with Relevance to Alzheimer’s Disease and Neurological Diseases
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  • Oct 2016
p class="jfr-body"> Food and nutrition guidelines for the handling and processing of fresh fruit, bread, and vegetables are essential and fresh produce may require cold preservation procedures to prevent minimal bacterial and fungi contamination of food. Bacterial lipopolysaccharides (LPS) corrupt lipoprotein and amyloid beta (Aβ) metabolism in diabetes, Alzheimer’s disease (AD) and various neurological diseases. In the developing world the increased plasma LPS levels induce non-alcoholic fatty liver diseases and interfere with albumin and Aβ interactions with spontaneous Aβ oligomer formation in the cerebrospinal fluid and brain that leads to neuron apoptosis by inactivation of Starling’s equation that is responsible for the maintenance of hydrostatic and oncotic pressure with relevance to fluid balance. In the developing world increased levels of LPS, mycotoxin and xenobiotics lead to irreversible neurological diseases by inhibition of Starling’s equation for maintenance of oncotic/osmotic pressure that lead to neuron senescence or apoptosis. In the developed world nutrigenomic diets are required that prevent Sirtuin 1 gene repression and maintain neuron survival that links the brain and peripheral hepatic monomer Aβ metabolism. The maintenance of blood-cerebrospinal fluid capillary transport of albumin and monomer Aβ is relevant to stabilization of neurons not only in Alzheimer’s disease but also in Type 3 diabetes and various neurological diseases. Healthy diets reverse the inhibition of brain to peripheral Aβ transport that is sensitive to Starling’s equation for regulation of central nervous system hydrostatic and oncotic pressure with the prevention of diabetes, various neurological diseases and Alzheimer’s disease. </p
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Human longevity: Genetics or Lifestyle? It takes two to tango
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Healthy aging and longevity in humans are modulated by a lucky combination of genetic and non-genetic factors. Family studies demonstrated that about 25 % of the variation in human longevity is due to genetic factors. The search for genetic and molecular basis of aging has led to the identification of genes correlated with the maintenance of the cell and of its basic metabolism as the main genetic factors affecting the individual variation of the aging phenotype. In addition, studies on calorie restriction and on the variability of genes associated with nutrient-sensing signaling, have shown that ipocaloric diet and/or a genetically efficient metabolism of nutrients, can modulate lifespan by promoting an efficient maintenance of the cell and of the organism. Recently, epigenetic studies have shown that epigenetic modifications, modulated by both genetic background and lifestyle, are very sensitive to the aging process and can either be a biomarker of the quality of aging or influence the rate and the quality of aging. On the whole, current studies are showing that interventions modulating the interaction between genetic background and environment is essential to determine the individual chance to attain longevity.
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