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EDITORIAL In the United States and Europe the geriatric population (> 65 years) is expected to double by the year 2060 with the death rate in the European Union in the geriatric population to be greater than 80% when compared with individuals < 65 years [1,2]. Geriatrics are susceptible to the global increase in chronic diseases with diabetes and neurodegenerative disease predicted to effect and determine the increased death rate of the geriatric population in the next 40 years. A defect in a single gene versus multi gene effects may be responsible for accelerated aging connected to mitochondrial apoptosis [3] and programmed cell death with relevance to insulin resistance and the increased death rate in geriatrics. The United States population is composed of white Americans, black/African Americans, native Americans, Alaska natives, Asian Americans, native Hawaiians/pacific islanders and Hispanic/Latino Americans [4]. The defect in a gene that may cause mitochondrial apoptosis in all these individuals and connected to insulin resistance identifies the heat shock gene Sirtuin 1 (Sirt 1) to be defective in these populations [5].
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Martins IJ. Curr Updates Gerontol. (2016) 1: 2.1
Current Updates in Gerontology
2
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Open Access Open Peer Review
Editorial Open Access
Geriatric Medicine and Heat Shock Gene Therapy in
Global Populaons
Marns IJ1,2,3*
1Centre of Excellence in Alzheimer’s Disease Re-
search and Care, School of Medical Sciences, Edith
Cowan University, Australia
2School of Psychiatry and Clinical Neurosciences,
The University of Western Australia, Australia
3McCusker Alzheimer's Research Foundaon, Holly-
wood Medical Centre, Australia
Copyright: © 2016 Ian Marns. This arcle is dis-
tributed under the terms of the Creave Commons
Aribuon 4.0 Internaonal License (hp://cre-
avecommons.org/licenses/by/4.0/), which permits
unrestricted use, distribuon, and reproducon in
any medium, provided you give appropriate credit
to the original author(s) and the source.
*Corresponding author: Ian Marns, School of Med-
ical Sciences, Edith Cowan University, 270 Joondalup
Drive, Joondalup, Western Australia 6027, Australia,
Tel: +61863042574; Email: i.marns@ecu.edu.au
Original Submission
Received: December 06, 2016
Accepted: December 15, 2016
Published: December 22, 2016
How to cite this arcle: Ian Marns. Geriatric Medi-
cine and Heat Shock Gene Therapy in Global Popu-
laons. Curr Updates Gerontol. (2016) 1: 2.1
Open Peer Review Status: Editorials, news items,
analysis arcles, and features do not undergo exter-
nal peer review.
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Current Updates in Gerontology
Open Access Open Peer Review Martins IJ. Curr Updates Gerontol. (2016) 1: 2.1
Keywords
Diabetes; Thermoregulaon Therapy; Mitochondria; Heat
Shock Gene; Geriatric; NAFLD; Fat Diet; Mitochondria; Caeine;
Bacterial Lipopolysaccharides
Editorial
In the United States and Europe the geriatric populaon
(> 65 years) is expected to double by the year 2060 with the
death rate in the European Union in the geriatric populaon
to be greater than 80% when compared with individuals < 65
years [1,2]. Geriatrics are suscepble to the global increase in
chronic diseases with diabetes and neurodegenerave disease
predicted to eect and determine the increased death rate of
the geriatric populaon in the next 40 years. A defect in a sin-
gle gene versus mul gene eects may be responsible for ac-
celerated aging connected to mitochondrial apoptosis [3] and
programmed cell death with relevance to insulin resistance and
the increased death rate in geriatrics.
Figure 1: In the United States and the European Union the increasing
geriatric populaon by the year 2060 has raised concern for the in-
creased death rates in 30% of these geriatric communies (30%) and
connected to the defecve heat shock gene Sirt 1 (human knockout).
Major interests in diet and lifestyle has escalated that may acvate Sirt
1 relevant to neuron survival and stabilizaon of chronic diseases with
possible reversal in 30 % of geriatric individuals. The global epidemic
for chronic diseases in the developing world idenes 40 % of geriat-
rics as the major populaon that are at increased risk for programmed
cell death with mulple organ diseases linked to Sirt 1 defects.
The United States populaon is composed of white Amer-
icans, black/African Americans, nave Americans, Alaska na-
ves, Asian Americans, nave Hawaiians/pacic islanders and
Hispanic/Lano Americans [4]. The defect in a gene that may
cause mitochondrial apoptosis in all these individuals and con-
nected to insulin resistance idenes the heat shock gene Sir-
tuin 1 (Sirt 1) to be defecve in these populaons [5]. Sirt 1 is a
niconamide adenine dinucleode dependent class III histone
deacetylase) that targets various transcripon factors involved
with insulin resistance, metabolic acvity and inammaon [6].
Recent interests in the role of Sirt 1 as a heat shock gene in-
dicates that thermoregulaon disorders as the inducing factor
with increased risk to geriatrics for the development of Type
3 diabetes, stroke, cardiovascular disease, non alcoholic fay
liver disease (NAFLD), hypertension and blood brain barrier dis-
ease [7,8]. Geriatrics in 30% of global communies (Figure 1)
that are induced with the various chronic diseases now indicate
the heat shock gene Sirt 1 to be defecve in these various com-
munies irrespecve of racial origin.
Major interests in geriatric medicine has accelerated with
diet and lifestyles changes that may stabilize mitochondrial
apoptosis [9] and organ diseases in these communies. In the
developing world increased plasma LPS levels have raised alarm
with relevance to thermoregulaon disorders [7] connected to
mitochondrial apoptosis relevant to NAFLD, myocardial infarc-
on and various organ diseases [6]. Sirt 1 and the heat shock
response involve the transcripon factor p53/PGC1 alpha, vari-
ous heat shock proteins and the heat shock transcripon factor
1 important to neuron survival and insulin receptor pathways
[7]. Sirt 1 regulaon of HSF1 is via PGC1 alpha that is a direct
transcripon repressor of HSF1 [3,10,11]. Geriatrics and brain
temperature regulaon may be defecve with relevance to Sirt
1 gene repression by LPS [12] and inducon of NAFLD with
increased transport to LPS to the brain [5].
Diets that contain fat may be metabolized rapidly in individ-
uals (< 65 years) compared with geriatrics with thermoregula-
on defects and defecve fat metabolism [8,13]. Consumpon
of fats such as palm oil (palmic acid rich) and virgin coconut
oil (saturated fay acids) [7] that are solid (20-24C) may be
sensive to abnormal body temperature dysregulaon with the
inducon of NAFLD (Figure 1) versus the consumpon of olive
oil (monounsaturated) that is liquid at a temperature (4C). Di-
etary fat restricon reduce LPS absorpon with relevance to
Sirt 1/p53 interacons that are essenal for uncoupling protein
1 (UCP1) expression [14] with Sirt 1 acvators important to ac-
vaon of thermogenesis related genes (PTEN, UCP1) [15].
In geriatrics the discovery of the heat shock gene Sirt 1
[3] has become important with relevance to the use of ther-
moregulaon drugs that maintain the thermoregulatory set
points in geriarcs [16]. Other drugs for depression and psy-
chosis [17,18] may be inacvated with relevance to thermoreg-
ulaon disorders with increased transport to the brain relevant
to defecve insulin therapy [19,20] that determines social in-
teracon and behaviour . In geriatrics Sirt 1 is responsible for
appete regulaon [6] and its loss from the suprachiasmac
nucleus in the hypothalamus of geriatrics result not only in cen-
tral neural thermoregulatory dysregulaon, circadian rhythm
abnormalies but also loss appete control (anorexia nervo-
sa) [21]. Caeine consumpon [22] in geriatrics without NAFLD
needs to be carefully determined to acvate hepac mitochon-
drial funcon that may improve post-prandial lipid metabolism
(Figure 1) aer consumpon of meals that contain fat. However
global Type 3 diabetes and neurodegenerave diseases may be
irreversible with relevance to long term caeine consumpon
Martins IJ. Curr Updates Gerontol. (2016) 1: 2.1
Current Updates in Gerontology
4
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Open Access Open Peer Review
in geriatrics. Caeine may be relevant to accelerated neuro-
degeneraon and crical changes to diet, lifestyles and ther-
moregulaon are required to prevent caeine induced neuro-
degeneraon. Geriatrics and links to NAFLD [8] now indicate
defecve caeine metabolism [23]. Caeine has been used to
improve mitochondrial thermogenesis [24,25] but with NAFLD
defecve caeine metabolism over years increases CNS caf-
feine transport with relevance to p53 mediated mitochondrial
death relevant to neuron apoptosis [26,27].
Conclusion
The global geriatric populaon by the year 2060 is ex-
pected to markedly increase and global death rate in geriatric
individuals is predicted to rise sharply and associated with mi-
tochondrial apoptosis in geriatric individuals with Type 3/Type
2 diabetes, NAFLD and neurodegenerave disease. The heat
shock gene Sirt 1 is crical to geriatric medicine with relevance
to appete regulaon, thermoregulaon disorders and defec-
ve post-prandial lipid metabolism. Fat consumpon such as
palm oil/coconut oil should be carefully evaluated before con-
sumpon in geriatric individuals (thermoregulaon disorders)
with relevance to delayed metabolism of these fats (solid at
body temperature) and the inducon of NAFLD. Diet, drug ther-
apy and lifestyle changes are a crical component for thermo-
regulatory adaptaons that allow reversal of accelerated aging
in geriatric individuals with the prevenon of programmed cell
death.
Acknowledgements
This work was supported by grants from Edith Cowan Uni-
versity, the McCusker Alzheimer's Research Foundaon and the
Naonal Health and Medical Research Council.
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... Sirt 1 is now referred as the gene involved in mitochondrial biogenesis that is critical to maintain cell function with the prevention of cell apoptosis [9][10][11][12][122][123][124][125]. Sirt 1 is critical to SCN function and the maintenance of core-body temperature with essential control of the adipose tissueliver crosstalk [131,150]. The consumption of coconut oil (saturated fat) and palm oil (palmitic acid) should be carefully evaluated in individuals with core-body temperature disorders. ...
... The consumption of coconut oil (saturated fat) and palm oil (palmitic acid) should be carefully evaluated in individuals with core-body temperature disorders. These fats are solid at temperatures between 20 and 24°C and with abnormal body temperature dysregulation may be involved in the induction of NAFLD when compared with the consumption of olive oil (monounsaturated) that is liquid at a temperature (4°C) [130,150]. Fish contains high levels of omega-3 fatty acids, docosahexaenoic acid (DHA 22:6n-3), and eicosapentaenoic acid (EPA 20:5n-3). These fatty acids are essential for liver fat metabolism with prevention of NAFLD [151,152] and brain function but with changes in core body temperature (Figure 7), therapeutic lipids essential for the prevention of NAFLD may be completely inactivated [130,131,150]. ...
... Fish contains high levels of omega-3 fatty acids, docosahexaenoic acid (DHA 22:6n-3), and eicosapentaenoic acid (EPA 20:5n-3). These fatty acids are essential for liver fat metabolism with prevention of NAFLD [151,152] and brain function but with changes in core body temperature (Figure 7), therapeutic lipids essential for the prevention of NAFLD may be completely inactivated [130,131,150]. Palmitic acid content in milk should be carefully controlled to allow the therapeutic effects of caffeine with relevance to mitochondrial thermogenesis and SCN regulation (Figure 7). ...
Book
Full-text available
Nutritional diets are essential to prevent nonalcoholic fatty liver disease (NAFLD) in the global obesity and diabetes epidemic. The ingestion of palmitic acid-rich diets induces NAFLD in animal and human studies. The beneficial properties of olive oil (oleic acid) may be superseded by ingestion of palmitic acid-rich diets. Hepatic caffeine metabolism is regulated by palmitic and oleic acid with effects of these fats on amyloid beta metabolism. Healthy fats such as olive oil may facilitate rapid amyloid beta clearance in the periphery to maintain drug therapy in diabetes and various neurological diseases. Repression of the anti-aging gene sirtuin 1 (Sirt 1) prevents the beneficial properties of olive oil. Brain disorders induce NAFLD and supersede caffeine’s therapeutic effects in the prevention of NAFLD. Delayed hepatic caffeine metabolism in NAFLD and increased caffeine transport to the brain with aging-induced mitophagy in neurons with induction of type 3 diabetes and neurodegenerative disease.
... Sirt 1 is now referred as the gene involved in mitochondrial biogenesis that is critical to maintain cell function with the prevention of cell apoptosis [9][10][11][12][122][123][124][125]. Sirt 1 is critical to SCN function and the maintenance of core-body temperature with essential control of the adipose tissueliver crosstalk [131,150]. The consumption of coconut oil (saturated fat) and palm oil (palmitic acid) should be carefully evaluated in individuals with core-body temperature disorders. ...
... The consumption of coconut oil (saturated fat) and palm oil (palmitic acid) should be carefully evaluated in individuals with core-body temperature disorders. These fats are solid at temperatures between 20 and 24°C and with abnormal body temperature dysregulation may be involved in the induction of NAFLD when compared with the consumption of olive oil (monounsaturated) that is liquid at a temperature (4°C) [130,150]. Fish contains high levels of omega-3 fatty acids, docosahexaenoic acid (DHA 22:6n-3), and eicosapentaenoic acid (EPA 20:5n-3). These fatty acids are essential for liver fat metabolism with prevention of NAFLD [151,152] and brain function but with changes in core body temperature (Figure 7), therapeutic lipids essential for the prevention of NAFLD may be completely inactivated [130,131,150]. ...
... Fish contains high levels of omega-3 fatty acids, docosahexaenoic acid (DHA 22:6n-3), and eicosapentaenoic acid (EPA 20:5n-3). These fatty acids are essential for liver fat metabolism with prevention of NAFLD [151,152] and brain function but with changes in core body temperature (Figure 7), therapeutic lipids essential for the prevention of NAFLD may be completely inactivated [130,131,150]. Palmitic acid content in milk should be carefully controlled to allow the therapeutic effects of caffeine with relevance to mitochondrial thermogenesis and SCN regulation (Figure 7). ...
Chapter
Full-text available
Nutritional diets are essential to prevent nonalcoholic fatty liver disease (NAFLD) in the global obesity and diabetes epidemic. The ingestion of palmitic acid-rich diets induces NAFLD in animal and human studies. The beneficial properties of olive oil (oleic acid) may be superseded by ingestion of palmitic acid-rich diets. Hepatic caffeine metabolism is regulated by palmitic and oleic acid with effects of these fats on amyloid beta metabolism. Healthy fats such as olive oil may facilitate rapid amyloid beta clearance in the periphery to maintain drug therapy in diabetes and various neurological diseases. Repression of the anti-aging gene sirtuin 1 (Sirt 1) prevents the beneficial properties of olive oil. Brain disorders induce NAFLD and supersede caffeine’s therapeutic effects in the prevention of NAFLD. Delayed hepatic caffeine metabolism in NAFLD and increased caffeine transport to the brain with aging-induced mitophagy in neurons with induction of type 3 diabetes and neurodegenerative disease.
... Specific foods that activate the heat shock gene have become important to global chronic disease and diets that contain fats such as palm oil (palmitic acid rich)/virgin coconut oil (saturated fatty acids) that are solid (20-24C) at body temperature may not be metabolized (liquid versus solid) with the induction of non alcoholic fatty liver disease (NAFLD) that has now reached a global epidemic. In man the geriatric population with body temperature dysregulation may involve complete heat shock gene Sirt 1 inactivation (Martins 2016a) and mitochondrial apoptosis (Fig. 3.1) relevant to defective hepatic fat/drug metabolism and NAFLD in the geriatric population. ...
... MicroRNA (miR) such as miR-34a, miR-122 and miR-132 are associated with Sirt 1 repression (Martins 2015a) and override body temperature regulation relevant to low adipose tissue adiponectin release and the development of core body temperature defects (Fig. 3.2), metabolic disease and NAFLD ( Fig. 3.2). Sirt 1/p53 interactions are essential for uncoupling protein 1 (UCP1) expression (Martins 2016a) and important to activation of thermogenesis related genes (Phosphatase and tensin homolog, UCP1) with miRNAs associated with inactivation of these thermogenesis genes. Mi-34a (Martins 2015a) may inactivate the Sirt1-adiponectin transcription in adipocytes by dysregulation of FOXO/CCAAT/enhancer-binding protein alpha (C/EBPalpha) that form a transcription complex at the mouse adiponectin promoter that up-regulates adiponectin gene transcription. ...
... Specific foods that activate the heat shock gene have become important to global chronic disease and diets that contain fats such as palm oil (palmitic acid rich)/virgin coconut oil (saturated fatty acids) that are solid (20-24C) at body temperature may not be metabolized (liquid versus solid) with the induction of non alcoholic fatty liver disease (NAFLD) that has now reached a global epidemic. In man the geriatric population with body temperature dysregulation may involve complete heat shock gene Sirt 1 inactivation (Martins, 2016a) and mitochondrial apoptosis relevant to defective hepatic fat/drug metabolism and NAFLD in the geriatric population. ...
... MicroRNA (miR) such as miR-34a, miR-122 and miR-132 are associated with Sirt 1 repression (Martins, 2015) and override body temperature regulation relevant to low adipose tissue adiponectin release and the development of core body temperature defects, metabolic disease and NAFLD. Sirt 1/p53 interactions are essential for uncoupling protein 1 (UCP1) expression (Martins, 2016a) and important to activation of thermogenesis related genes (Phosphatase and tensin homolog, UCP1) with miRNAs associated with inactivation of these thermogenesis genes. Mi-34a (Martins, 2015) Temperature variations in organisms have marked changes in body metabolism with higher temperatures associated with increased ageing. ...
Chapter
Full-text available
Temperature variations in various species have marked changes in body metabolism with higher temperatures associated with increased ageing. The observation that diets with calorie restriction are associated with species longevity are now related to the heat shock genes and body temperature regulation. Temperature increases that induce temperature dysregulation are connected to non alcoholic fatty liver disease (NAFLD) and the induction of diabetes and neurodegenerative diseases. Specific microRNAs are associated with heat shock gene regulation and override body temperature regulation relevant to adipose tissue-liver defects and insulin resistance. In geriatrics and diabetics complete heat shock gene inactivation is associated with mitochondrial apoptosis relevant to defective hepatic dietary fat and drug metabolism. The connections between core body temperature defects and autoimmune disease have now become important to determine programmed cell death in many cells and tissues with relevance to the global chronic disease epidemic and species survival.
... these individuals [12]. Plasma bacterial Lipopolysaccharides (LPS) have risen markedly [13] in individuals in the developing world and the relationship between LPS and the repression of the heat shock gene Sirtuin 1 (Sirt 1) has been reported with relevance to NAFLD and diabetes [14][15][16][17]. LPS induces NAFLD and the relevance of dietary fat such as virgin coconut oil/palm oil consumption [14] should be carefully controlled to prevent insulin resistance and accelerated NAFLD. ...
... Plasma bacterial Lipopolysaccharides (LPS) have risen markedly [13] in individuals in the developing world and the relationship between LPS and the repression of the heat shock gene Sirtuin 1 (Sirt 1) has been reported with relevance to NAFLD and diabetes [14][15][16][17]. LPS induces NAFLD and the relevance of dietary fat such as virgin coconut oil/palm oil consumption [14] should be carefully controlled to prevent insulin resistance and accelerated NAFLD. Individuals in the developing world are more susceptible to NAFLD and diabetes and the heat shock response by LPS is involved in the transformation of liver cells (NAFLD) [13] and associated with defective heat stress response that involves the Sirt 1/HSF1 interaction [18]. ...
Article
Full-text available
The use of heat therapy in individuals with obesity and Type 2 diabetes mellitus has become an important treatment for metabolic and cardiovascular diseases [1-5] for individuals in the developing and developed world. The cellular response to heat therapy includes the transcriptional up-regulation of genes encoding Heat Shock Proteins (HSPs) as part of the cell’s internal repair mechanism [6,7]. These stress-proteins respond to heat, cold and oxygen deprivation by activating several cascade pathways that may be relevant to survival and apoptosis of mitochondria in cells [8]. Heat therapy has been used with the plasma analysis of adiponectin, AMP-Activated Protein Kinase (AMPK), Heat Shock Factor 1 (HSF1), Heat Shock Protein (HSP) 27, HSP70, and HSP90 important as markers for heat stress therapy [9]. Diabetes that previously has involved pancreatic disease in Type 2 diabetic individuals [10] now involves global Non Alcoholic Fatty Liver Disease (NAFLD) with heat therapy critical to improvement in hepatic insulin resistance [11] in obese/diabetic individuals
... Environmental factors such as stress, anxiety and depression are important to consider in many communities with the global increase in chronic diseases [12][13][14] and brain metabolic diseases associated with malfunction of the gene Sirtuin 1 (Sirt 1) that regulates immunometabolism [15]. Analysis of biomarkers may indicate immunometabolism disorders [16] with epigenetic alterations and autoimmunity disorders (Figure 1) that may supersede the connections between plasma biomarkers related to accelerated ageing in geriatric disease [17] and ageing science. The stress sensitive gene Sirt 1 [14] may be completely repressed in these individuals with the defective immune system related to heat shock protein (HSP) metabolism, autoimmunity and mitophagy (Figure 1). ...
Article
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The science of ageing has become of critical interest and the anti-ageing market now relevant to geriatric medicine with nutritional diets and lifestyles changes that may stabilize mitochondrial apoptosis and organ diseases in these communities. The assessment of healthy ageing has created several difficulties with interpretation from various biomarker studies that biomarker analysis may not necessarily translate to diagnosis. Comprehensive review of the literature have been conducted with biomarkers that may be relevant to five age related domains and include physical/cognitive capability, physiological/musculoskeletal, endocrine and immune functions . The comprehensive assessment of these biomarkers may allow interpretations of the science of ageing but may not allow the diagnosis of programmed cell death with mitophagy as the inevitable defect in the geriatric population.
... Hepatic pharmacokinetics associated with blood and brain drug levels require the activation of the calorie sensitive gene Sirtuin 1 (Sirt 1) to prevent circadian rhythm imbalances that interfere with brain interactions with hepatic drug metabolism [2,6-8]. Sirt 1 is now referred to as the heat shock gene [9][10][11] with its critical role in the metabolism of heat shock proteins (HSPs) such as HSP 60, 70 and 90 [12]. Sirt 1 is involved in suprachiasmatic nucleus regulation [2,6] with relevance to core brain temperature control in man and cattle [7,8]. ...
Article
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Drug and endocrine therapy to delay the complications of obesity and diabetes has escalated with the use of chronic disease medications to improve therapy in the presence of ER stress induced mitophagy. Nutrient assessment in diabetes has increased to activate the heat shock gene Sirt 1 and to prevent ER stress that may be the critical to the prevention of drug induced toxicity, ER stress and mitophagy. Heat therapy may lead to inactivation of the heat shockgene Sirt 1 with inactivation of various critical drug and endocrine therapies essential for multiple organ dysfunction syndrome.
... The p53 is involved in immune responses, metabolism and mitochondrial apoptosis [23][24][25][26][27][28][29][30][31]with diet, drugs and environment [32] critical to the regulation of Sirt 1/p53 immnometabolism and induction of NAFLD in the developed world. Thermoregulation defects in geriatric populations [33] indicate immune response alterations [34] that accelerate various chronic diseases in these individuals. Autoimmune disorders in the geriatric populations have been described and the heat shock gene Sirt 1 defective in these populations [35,36] may indicate connections between defective thermoregulation and automimmune diseases [37][38][39][40]. ...
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