\documentclass[11pt,twoside]{article}\makeatletter \IfFileExists{xcolor.sty}% {\RequirePackage{xcolor}}% {\RequirePackage{color}} \usepackage{colortbl} \usepackage{wrapfig} \usepackage{ifxetex} \ifxetex \usepackage{fontspec} \usepackage{xunicode} \catcode`⃥=\active \def⃥{\textbackslash} \catcode`❴=\active \def❴{\{} \catcode`❵=\active \def❵{\}} \def\textJapanese{\fontspec{Noto Sans CJK JP}} \def\textChinese{\fontspec{Noto Sans CJK SC}} \def\textKorean{\fontspec{Noto Sans CJK KR}} \setmonofont{DejaVu Sans Mono} \else \IfFileExists{utf8x.def}% {\usepackage[utf8x]{inputenc} \PrerenderUnicode{–} }% {\usepackage[utf8]{inputenc}} \usepackage[english]{babel} \usepackage[T1]{fontenc} \usepackage{float} \usepackage[]{ucs} \uc@dclc{8421}{default}{\textbackslash } \uc@dclc{10100}{default}{\{} \uc@dclc{10101}{default}{\}} \uc@dclc{8491}{default}{\AA{}} \uc@dclc{8239}{default}{\,} \uc@dclc{20154}{default}{ } \uc@dclc{10148}{default}{>} \def\textschwa{\rotatebox{-90}{e}} \def\textJapanese{} \def\textChinese{} \IfFileExists{tipa.sty}{\usepackage{tipa}}{} \fi \def\exampleFont{\ttfamily\small} \DeclareTextSymbol{\textpi}{OML}{25} \usepackage{relsize} \RequirePackage{array} \def\@testpach{\@chclass \ifnum \@lastchclass=6 \@ne \@chnum \@ne \else \ifnum \@lastchclass=7 5 \else \ifnum \@lastchclass=8 \tw@ \else \ifnum \@lastchclass=9 \thr@@ \else \z@ \ifnum \@lastchclass = 10 \else \edef\@nextchar{\expandafter\string\@nextchar}% \@chnum \if \@nextchar c\z@ \else \if \@nextchar l\@ne \else \if \@nextchar r\tw@ \else \z@ \@chclass \if\@nextchar |\@ne \else \if \@nextchar !6 \else \if \@nextchar @7 \else \if \@nextchar (8 \else \if \@nextchar )9 \else 10 \@chnum \if \@nextchar m\thr@@\else \if \@nextchar p4 \else \if \@nextchar b5 \else \z@ \@chclass \z@ \@preamerr \z@ \fi \fi \fi \fi \fi \fi \fi \fi \fi \fi \fi \fi \fi \fi \fi \fi} \gdef\arraybackslash{\let\\=\@arraycr} \def\@textsubscript#1{{\m@th\ensuremath{_{\mbox{\fontsize\sf@size\z@#1}}}}} \def\Panel#1#2#3#4{\multicolumn{#3}{){\columncolor{#2}}#4}{#1}} \def\abbr{} \def\corr{} \def\expan{} \def\gap{} \def\orig{} \def\reg{} \def\ref{} \def\sic{} \def\persName{}\def\name{} \def\placeName{} \def\orgName{} \def\textcal#1{{\fontspec{Lucida Calligraphy}#1}} \def\textgothic#1{{\fontspec{Lucida Blackletter}#1}} \def\textlarge#1{{\large #1}} \def\textoverbar#1{\ensuremath{\overline{#1}}} \def\textquoted#1{‘#1’} \def\textsmall#1{{\small #1}} \def\textsubscript#1{\@textsubscript{\selectfont#1}} \def\textxi{\ensuremath{\xi}} \def\titlem{\itshape} \newenvironment{biblfree}{}{\ifvmode\par\fi } \newenvironment{bibl}{}{} \newenvironment{byline}{\vskip6pt\itshape\fontsize{16pt}{18pt}\selectfont}{\par } \newenvironment{citbibl}{}{\ifvmode\par\fi } \newenvironment{docAuthor}{\ifvmode\vskip4pt\fontsize{16pt}{18pt}\selectfont\fi\itshape}{\ifvmode\par\fi } \newenvironment{docDate}{}{\ifvmode\par\fi } \newenvironment{docImprint}{\vskip 6pt}{\ifvmode\par\fi } \newenvironment{docTitle}{\vskip6pt\bfseries\fontsize{22pt}{25pt}\selectfont}{\par } \newenvironment{msHead}{\vskip 6pt}{\par} \newenvironment{msItem}{\vskip 6pt}{\par} \newenvironment{rubric}{}{} \newenvironment{titlePart}{}{\par } \newcolumntype{L}[1]{){\raggedright\arraybackslash}p{#1}} \newcolumntype{C}[1]{){\centering\arraybackslash}p{#1}} \newcolumntype{R}[1]{){\raggedleft\arraybackslash}p{#1}} \newcolumntype{P}[1]{){\arraybackslash}p{#1}} \newcolumntype{B}[1]{){\arraybackslash}b{#1}} \newcolumntype{M}[1]{){\arraybackslash}m{#1}} \definecolor{label}{gray}{0.75} \def\unusedattribute#1{\sout{\textcolor{label}{#1}}} \DeclareRobustCommand*{\xref}{\hyper@normalise\xref@} \def\xref@#1#2{\hyper@linkurl{#2}{#1}} \begingroup \catcode`\_=\active \gdef_#1{\ensuremath{\sb{\mathrm{#1}}}} \endgroup \mathcode`\_=\string"8000 \catcode`\_=12\relax \usepackage[a4paper,twoside,lmargin=1in,rmargin=1in,tmargin=1in,bmargin=1in,marginparwidth=0.75in]{geometry} \usepackage{framed} \definecolor{shadecolor}{gray}{0.95} \usepackage{longtable} \usepackage[normalem]{ulem} \usepackage{fancyvrb} \usepackage{fancyhdr} \usepackage{graphicx} \usepackage{marginnote} \renewcommand{\@cite}[1]{#1} \renewcommand*{\marginfont}{\itshape\footnotesize} \def\Gin@extensions{.pdf,.png,.jpg,.mps,.tif} \pagestyle{fancy} \usepackage[pdftitle={Early Diagnosis of Neuron Mitochondrial Dysfunction May Reverse Global Metabolic and Neurodegenerative Disease}, pdfauthor={}]{hyperref} \hyperbaseurl{} \paperwidth210mm \paperheight297mm \def\@pnumwidth{1.55em} \def\@tocrmarg {2.55em} \def\@dotsep{4.5} \setcounter{tocdepth}{3} \clubpenalty=8000 \emergencystretch 3em \hbadness=4000 \hyphenpenalty=400 \pretolerance=750 \tolerance=2000 \vbadness=4000 \widowpenalty=10000 \renewcommand\section{\@startsection {section}{1}{\z@}% {-1.75ex \@plus -0.5ex \@minus -.2ex}% {0.5ex \@plus .2ex}% {\reset@font\Large\bfseries}} \renewcommand\subsection{\@startsection{subsection}{2}{\z@}% {-1.75ex\@plus -0.5ex \@minus- .2ex}% {0.5ex \@plus .2ex}% {\reset@font\Large}} \renewcommand\subsubsection{\@startsection{subsubsection}{3}{\z@}% {-1.5ex\@plus -0.35ex \@minus -.2ex}% {0.5ex \@plus .2ex}% {\reset@font\large}} \renewcommand\paragraph{\@startsection{paragraph}{4}{\z@}% {-1ex \@plus-0.35ex \@minus -0.2ex}% {0.5ex \@plus .2ex}% {\reset@font\normalsize}} \renewcommand\subparagraph{\@startsection{subparagraph}{5}{\parindent}% {1.5ex \@plus1ex \@minus .2ex}% {-1em}% {\reset@font\normalsize\bfseries}} \def\l@section#1#2{\addpenalty{\@secpenalty} \addvspace{1.0em plus 1pt} \@tempdima 1.5em \begingroup \parindent \z@ \rightskip \@pnumwidth \parfillskip -\@pnumwidth \bfseries \leavevmode #1\hfil \hbox to\@pnumwidth{\hss #2}\par \endgroup} \def\l@subsection{\@dottedtocline{2}{1.5em}{2.3em}} \def\l@subsubsection{\@dottedtocline{3}{3.8em}{3.2em}} \def\l@paragraph{\@dottedtocline{4}{7.0em}{4.1em}} \def\l@subparagraph{\@dottedtocline{5}{10em}{5em}} \@ifundefined{c@section}{\newcounter{section}}{} \@ifundefined{c@chapter}{\newcounter{chapter}}{} \newif\if@mainmatter \@mainmattertrue \def\chaptername{Chapter} \def\frontmatter{% \pagenumbering{roman} \def\thechapter{\@roman\c@chapter} \def\theHchapter{\roman{chapter}} \def\thesection{\@roman\c@section} \def\theHsection{\roman{section}} \def\@chapapp{}% } \def\mainmatter{% \cleardoublepage \def\thechapter{\@arabic\c@chapter} \setcounter{chapter}{0} \setcounter{section}{0} \pagenumbering{arabic} \setcounter{secnumdepth}{6} \def\@chapapp{\chaptername}% \def\theHchapter{\arabic{chapter}} \def\thesection{\@arabic\c@section} \def\theHsection{\arabic{section}} } \def\backmatter{% \cleardoublepage \setcounter{chapter}{0} \setcounter{section}{0} \setcounter{secnumdepth}{2} \def\@chapapp{\appendixname}% \def\thechapter{\@Alph\c@chapter} \def\theHchapter{\Alph{chapter}} \appendix } \newenvironment{bibitemlist}[1]{% \list{\@biblabel{\@arabic\c@enumiv}}% {\settowidth\labelwidth{\@biblabel{#1}}% \leftmargin\labelwidth \advance\leftmargin\labelsep \@openbib@code \usecounter{enumiv}% \let\p@enumiv\@empty \renewcommand\theenumiv{\@arabic\c@enumiv}% }% \sloppy \clubpenalty4000 \@clubpenalty \clubpenalty \widowpenalty4000% \sfcode`\.\@m}% {\def\@noitemerr {\@latex@warning{Empty `bibitemlist' environment}}% \endlist} \def\tableofcontents{\section*{\contentsname}\@starttoc{toc}} \parskip0pt \parindent1em \def\Panel#1#2#3#4{\multicolumn{#3}{){\columncolor{#2}}#4}{#1}} \newenvironment{reflist}{% \begin{raggedright}\begin{list}{} {% \setlength{\topsep}{0pt}% \setlength{\rightmargin}{0.25in}% \setlength{\itemsep}{0pt}% \setlength{\itemindent}{0pt}% \setlength{\parskip}{0pt}% \setlength{\parsep}{2pt}% \def\makelabel##1{\itshape ##1}}% } {\end{list}\end{raggedright}} \newenvironment{sansreflist}{% \begin{raggedright}\begin{list}{} {% \setlength{\topsep}{0pt}% \setlength{\rightmargin}{0.25in}% \setlength{\itemindent}{0pt}% \setlength{\parskip}{0pt}% \setlength{\itemsep}{0pt}% \setlength{\parsep}{2pt}% \def\makelabel##1{\upshape ##1}}% } {\end{list}\end{raggedright}} \newenvironment{specHead}[2]% {\vspace{20pt}\hrule\vspace{10pt}% \phantomsection\label{#1}\markright{#2}% \pdfbookmark[2]{#2}{#1}% \hspace{-0.75in}{\bfseries\fontsize{16pt}{18pt}\selectfont#2}% }{} \def\TheFullDate{2016-01-15 (revised: 15 January 2016)} \def\TheID{\makeatother } \def\TheDate{2016-01-15} \title{Early Diagnosis of Neuron Mitochondrial Dysfunction May Reverse Global Metabolic and Neurodegenerative Disease} \author{}\makeatletter \makeatletter \newcommand*{\cleartoleftpage}{% \clearpage \if@twoside \ifodd\c@page \hbox{}\newpage \if@twocolumn \hbox{}\newpage \fi \fi \fi } \makeatother \makeatletter \thispagestyle{empty} \markright{\@title}\markboth{\@title}{\@author} \renewcommand\small{\@setfontsize\small{9pt}{11pt}\abovedisplayskip 8.5\p@ plus3\p@ minus4\p@ \belowdisplayskip \abovedisplayskip \abovedisplayshortskip \z@ plus2\p@ \belowdisplayshortskip 4\p@ plus2\p@ minus2\p@ \def\@listi{\leftmargin\leftmargini \topsep 2\p@ plus1\p@ minus1\p@ \parsep 2\p@ plus\p@ minus\p@ \itemsep 1pt} } \makeatother \fvset{frame=single,numberblanklines=false,xleftmargin=5mm,xrightmargin=5mm} \fancyhf{} \setlength{\headheight}{14pt} \fancyhead[LE]{\bfseries\leftmark} \fancyhead[RO]{\bfseries\rightmark} \fancyfoot[RO]{} \fancyfoot[CO]{\thepage} \fancyfoot[LO]{\TheID} \fancyfoot[LE]{} \fancyfoot[CE]{\thepage} \fancyfoot[RE]{\TheID} \hypersetup{citebordercolor=0.75 0.75 0.75,linkbordercolor=0.75 0.75 0.75,urlbordercolor=0.75 0.75 0.75,bookmarksnumbered=true} \fancypagestyle{plain}{\fancyhead{}\renewcommand{\headrulewidth}{0pt}} \date{} \usepackage{authblk} \providecommand{\keywords}[1] { \footnotesize \textbf{\textit{Index terms---}} #1 } \usepackage{graphicx,xcolor} \definecolor{GJBlue}{HTML}{273B81} \definecolor{GJLightBlue}{HTML}{0A9DD9} \definecolor{GJMediumGrey}{HTML}{6D6E70} \definecolor{GJLightGrey}{HTML}{929497} \renewenvironment{abstract}{% \setlength{\parindent}{0pt}\raggedright \textcolor{GJMediumGrey}{\rule{\textwidth}{2pt}} \vskip16pt \textcolor{GJBlue}{\large\bfseries\abstractname\space} }{% \vskip8pt \textcolor{GJMediumGrey}{\rule{\textwidth}{2pt}} \vskip16pt } \usepackage[absolute,overlay]{textpos} \makeatother \usepackage{lineno} \linenumbers \begin{document} \author[1]{Martins IJ} \affil[1]{ The University of Western Australia} \renewcommand\Authands{ and } \date{\small \em Received: 9 December 2015 Accepted: 5 January 2016 Published: 15 January 2016} \maketitle \begin{abstract} The rise in obesity and diabetes in various countries have reached epidemic proportions [1]with the inability of the brain to regulate body weight and energy balance in the early part of life and related to neurodegenerative disease in these countries. Neurons in the brain become sensitive to Western diets with alterations in neurons that lead to brain circuitry disorders or feeding signals [2]. In insulin resistance and neurodegenerative diseases the astrocyte-neuron interaction is defective in the brain [3] and consumption of a Western diet does not allow neurons to metabolize glucose and fatty acids but instead leads to mitochondrial apoptosis and programmed neuron death. In the periphery in global communities liver steatosis can be reversible with hepatocyte mitochondria still able to metabolize fatty acids and glucose after consumption of a healthy low calorie diet but in the brain neuron mitochondria may not continue with mitochondrial biogenesis but continue to undergo apoptosis with neuron death. Networks between various brain cells involve membrane and nuclear lipid signals with diets involved in the regulation, transmission and communication between various brain cells. The three main types of glial cells are the astrocytes, oligodendrocytes and microglia with astrocytes involved with the maintenance of endothelial cells in brain capillaries and the blood brain barrier (BBB) to prevent toxic substances and their entry into the brain with the prevention of mitochondrial apoptosis in neurons. Astrocytes have been shown to be important to neuron lifespan and survival [4,5] with diets and lifestyle involved with epigenetic modification that disrupt astrocyte signalling [3] involved in the maintenance of neurons in individuals in global populations. Nutritional diets that prevent epigenetic alterations include DNA methylation, covalent histone modification and non-coding RNAs that are involved in gene activation and repression with chromatin structure modifica \end{abstract} \keywords{} \begin{textblock*}{18cm}(1cm,1cm) % {block width} (coords) \textcolor{GJBlue}{\LARGE Global Journals \LaTeX\ JournalKaleidoscope\texttrademark} \end{textblock*} \begin{textblock*}{18cm}(1.4cm,1.5cm) % {block width} (coords) \textcolor{GJBlue}{\footnotesize \\ Artificial Intelligence formulated this projection for compatibility purposes from the original article published at Global Journals. However, this technology is currently in beta. \emph{Therefore, kindly ignore odd layouts, missed formulae, text, tables, or figures.}} \end{textblock*} \let\tabcellsep& \section[{Editorial}]{Editorial} \section[{Early Diagnosis of Neuron Mitochondrial Dysfunction May Reverse Global Metabolic and}]{Early Diagnosis of Neuron Mitochondrial Dysfunction May Reverse Global Metabolic and}\par Neurodegenerative Disease\par Martins IJ \section[{Editorial}]{Editorial}\par The rise in obesity and diabetes in various countries have reached epidemic proportions \hyperref[b0]{[1]} with the inability of the brain to regulate body weight and energy balance in the early part of life and related to neurodegenerative disease in these countries. Neurons in the brain become sensitive to Western diets with alterations in neurons that lead to brain circuitry disorders or feeding signals \hyperref[b1]{[2]}. In insulin resistance and neurodegenerative diseases the astrocyte-neuron interaction is defective in the brain \hyperref[b2]{[3]} and consumption of a Western diet does not allow neurons to metabolize glucose and fatty acids but instead leads to mitochondrial apoptosis and programmed neuron death. In the periphery in global communities liver steatosis can be reversible with hepatocyte mitochondria still able to metabolize fatty acids and glucose after consumption of a healthy low calorie diet but in the brain neuron mitochondria may not continue with mitochondrial biogenesis but continue to undergo apoptosis with neuron death.\par Networks between various brain cells involve membrane and nuclear lipid signals with diets involved in the regulation, transmission and communication between various brain cells. The three main types of glial cells are the astrocytes, oligodendrocytes and microglia with astrocytes involved with the maintenance of endothelial cells in brain capillaries and the blood brain barrier (BBB) to prevent toxic substances and their entry into the brain with the prevention of mitochondrial apoptosis in neurons. Astrocytes have been shown to be important to neuron lifespan and survival \hyperref[b3]{[4,}\hyperref[b4]{5]} with diets and lifestyle involved with epigenetic modification that disrupt astrocyte signalling \hyperref[b2]{[3]} involved in the maintenance of neurons in individuals in global populations. Nutritional diets that prevent epigenetic alterations include DNA methylation, covalent histone modification and non-coding RNAs that are involved in gene activation and repression with chromatin structure modifications associated withintact circadian regulation critical for the increased survival of astrocytes and neurons. Atherogenic diets that stimulate bacterial lipopolysaccharides (LPS), mycotoxin and xenobiotics into the central nervous system may induce various cellular stresses with the induction of mitochondrial apoptosis induced neurodegenerative diseases.\par The increased global susceptibility to insulin resistance associated with brain aging and neurodegenerative diseases now indicate neuron vulnerability to senescence or apoptosis \hyperref[b5]{[6]}and require early plasma biomarker diagnosis that may assist with reversal of neuron senescence to healthy neurons that may be interpreted from lipidomic tests, genomic tests and proteomic tests \hyperref[b6]{[7]}. The information provided from these tests now are relevant to the early diagnosis of neuron senescence and linked to mitochondrial biogenesis versus mitochondrial apoptosis that determine the lifespan of neurons. The tests may further assist in novel and important Alzheimer's disease therapeutics that reverse amyloid beta oligomers damage to neuronsin diabetes related neurodegenerative disease and Alzheimer's disease \hyperref[b7]{[8]}.\par Figure {\ref 1}: Downregulation of the calorie sensitive gene Sirtuin 1 is important to mitochondrial biogenesis with Sirt 1/pr53 regulation of other anti-aging genes such as Klotho, p66shc, Foxo3a and the anti-aging transcription factor PGC1-alpha involved in mitochondrial function. Plasma protein analysis for the diagnosis of neuron mitochondrial function has become important with neurodegeneration closely linked to the global diabetic epidemic, NAFLD and various chronic diseases. Proteins such as apelin, angiotensin II, gelsolin, heat shock proteins, thrombospondin 1, transforming growth factor beta, tumour necrosis factor alpha, insulin like growth factor 1, fibroblast growth factor 21, adiponectin, GDF11 and hepatocyte growth factorare involved with mitochondrial survival and may involve p53 regulation of mitochondrial function in metabolic and neurodegenerative diseases.\par Genomic analysis now indicate that the antiaging gene Sirtuin 1 (Sirt 1) regulates other anti-aging genes that are now critical to mitochondrial biogenesis and neuron proliferation \hyperref[b7]{[8]}. Sirt 1's regulation of mitochondria involve p53 regulation and include other anti-aging genes (Figure {\ref 1}) that synthesize the Klotho anti-aging protein, p66shc longevity protein and transcription factors such as Forkhead box O3(FOXO3a) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1 apha) that are essential for the maintenance of mitochondrial function in cells \hyperref[b8]{[9]}\hyperref[b9]{[10]}\hyperref[b10]{[11]}. In Figure {\ref 1} the plasma proteome analysis of various proteins may now indicate the diagnosis of neuron apoptosis versus neuron survival from the determination of plasma proteins that are relevant to mitochondrial biogenesis versus mitochondrial apoptosis. The plasma proteome analysis for neuron survival that involve mitochondrial health include proteins such as apelin, angiotensin II, gelsolin, heat shock proteins (HSP 70, HSP 60), thrombospondin 1 (TSP-1), Transforming growth factor beta (TGF beta), Tumour necrosis factor alpha (TNF alpha), Insulin like growth factor 1 (IGF-1), Fibroblast growth factor 21 (FGF21), adiponectin, GDF11 and hepatocyte growth factor (HGF). Dysregulated crosstalk between the adipose tissue and the liver \hyperref[b9]{[10]} alter the release of these proteins with low and defective transport of these proteins to neurons in the brain relevant to increased mitochondrial senescence versus mitochondrial biogenesis.\par The gene-environment interaction identifies Sirt 1 in many global populations as the defective gene involved in the defective nuclear-mitochondria interactions in the adipose tissue and the liver relevant to the mitochondrial theory of aging \hyperref[b11]{[12]}\hyperref[b12]{[13]}\hyperref[b13]{[14]}.Sirt 1 (nicotinamide adenine dinucleotide dependent class III histone deacetylase) targets transcription factors such as peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC 1-), p53, pregnane X receptor (PXR), peroxisome proliferator-activated receptor (PPAR) to adapt gene expression to mitochondrial function with relevance to metabolic activity, insulin resistance and inflammation. Sirt 1 is involved in chromatin remodelling with effects on the nuclear and mitochondria interactions that determine neuron proliferation via mitochondrial biogenesis by deacetylation of PGC 1 alpha and p53 transcription factors that are important to mitochondrial DNA homeostasis \hyperref[b14]{[15]}\hyperref[b15]{[16]}\hyperref[b16]{[17]}\hyperref[b17]{[18]}\hyperref[b18]{[19]}. Sirt 1's regulation of circadian clocks regulate mitochondrial function that determine neuron synaptic plasticity in various neurological diseases \hyperref[b9]{[10,}\hyperref[b19]{[20]}\hyperref[b20]{[21]}\hyperref[b21]{[22]}\hyperref[b22]{[23]}\hyperref[b23]{[24]} {\ref [25]} {\ref [26]} {\ref [27]} {\ref [28]} {\ref [29]} {\ref [30]} {\ref [31]} {\ref [32]} {\ref [33]} {\ref [34]}. Major commercial interests in simple proteome tests that can be conducted in any routine laboratory may now indicate from plasma proteome analysis the proliferation of mitochondria with relevance to neuron survival and prevention of programmed cell death. In the current global non alcoholic fatty liver disease (NAFLD) epidemic the various proteins are important to neuron mitochondrial biogenesis and alterations in these proteins in the blood plasma may be involved in mitochondrial apoptosis and determine early neuron cell death. Sirt 1 and Sirt 3 are both involved with neuron mitochondria function with Sirt 1's important role in circadian regulation of Sirt 3's regulation of mitochondrial function {\ref [35,} {\ref 36]}.However with the aging process various plasma proteins are now relevant to mitochondrial health by the regulation of Sirt 1/p53 expression (Figure {\ref 1}) that may involve astrocyte regulation of mitochondrial biogenesis versus apoptosis that determine synaptic dysfunction and neurodegeneration {\ref [37]} {\ref [38]} {\ref [39]}.\par HGF has also been shown to be important to neuron and axon survival with relevance to HGF in p53 transcriptional regulation and mitochondrial biogenesis {\ref [40]} {\ref [41]} {\ref [42]} {\ref [43]} {\ref [44]} {\ref [45]} {\ref [46]} {\ref [47]} {\ref [48]} {\ref [49]} \hyperref[b33]{[76,}\hyperref[b34]{77]} with its connections to Sirt 1/IGF-1/GH regulation by diet and nutrition \hyperref[b35]{[78]}. TNF alpha \hyperref[b36]{[79]} is particularly sensitive to mitochondrial induced neuronal apoptosis and with TGF beta \hyperref[b37]{[80]} overide Sirt 1'scontrol of circadian regulation with relevance to mitochondrial related neuron apoptosis \hyperref[b38]{[81,}\hyperref[b39]{82]}.\par Adiponectin levels are closely connected to mitochondrial biogenesis with Sirt 1 regulation important toadiponection gene expression \hyperref[b40]{[83]}\hyperref[b41]{[84]}\hyperref[b42]{[85]}\hyperref[b43]{[86]}\hyperref[b44]{[87]}. Plasma TSP1 levels have become important to mitochondrial apoptosis with levels of LPS involved in TSP1 regulation and Sirt 1 repression \hyperref[b6]{[7]}. TSP1effects on CD47 receptor to prevent mitochondrial biogenesis and TSP-1 effects on p53 expression override Sirt 1/p53 transcriptional regulation of neuron synapticity and survival \hyperref[b45]{[88]}\hyperref[b46]{[89]}\hyperref[b47]{[90]}\hyperref[b48]{[91]}\hyperref[b49]{[92]}\hyperref[b50]{[93]}. Sirt 1 regulation of brain derived neurotrophic factor (BDNF) is now important to BDNF induced mitochondrial function and synaptic plasticity \hyperref[b8]{[9]}. Early analysis of plasma proteins (Figure {\ref 1}) that determine mitochondrial survival by p53 transcriptional regulation may now be important to Sirt 1 metabolism of toxic oligomers such as amyloid beta and alpha synuclein in neurodegenerative diseases \hyperref[b8]{[9,}\hyperref[b9]{10]}.\par Furthermore plasma lipidomic analysis allow interpretation that in insulin resistance and neurodegenerative diseases the increased plasma ceramides and sphingosine 1 phosphate are associated with increased liver/neuron mitochondrial apoptosis with programmed cell death of neurons associated with Sirt 1 repression. Lipids such as ceramides have been shown to inhibit Sirt 1/p53 transcriptional regulation and induce cell death in neurons or hepatocytes \hyperref[b51]{[94,}\hyperref[b52]{95]}. In contrast sphingosine 1 phosphate may act as a Sirt 1 activator by actions on increased PGC1alpha levels with increased mitochondrial biogenesis \hyperref[b53]{[96]}. Ceramides supersede the effects of various plasma proteins (Figure {\ref 1}) that have been shown to regulate p53 transcriptional activityto prevent mitochondrial apoptosis with relevance to neuron differentiation with plasma ceramide levels important to mitochondrial related defects in synaptic plasticity and neurodegeneration \hyperref[b2]{[3,}\hyperref[b6]{7]}. Nutritional therapy is required to promote the nuclear-mitochondria interaction andprevent mitochondrial apoptosis with improvement in the astrocyte-neuron crosstalk that determines the lifespan of neurons \hyperref[b54]{[97]}. Diet and nutrition is particularly relevant to neuron Sirt 1 regulation of the circadian rhythm with relevance to mitochondrial biogenesis and the prevention of high glucose induced mitochondrial dysfunction in neurons \hyperref[b55]{[98]}. The effects of high fat diets that contain palmitic acid induce liver steatosis and steastosis may be reversible but accelerated mitochondrial disease in neurons \hyperref[b56]{[99]}\hyperref[b57]{[100]}\hyperref[b58]{[101]}\hyperref[b59]{[102]}\hyperref[b60]{[103]} by palmitic acid as a Sirt 1 inhibitor may induce irreversible neurodegenerative disease {\ref [53]}. Nutriproteomic diets \hyperref[b6]{[7]} have become important by the release from the adipose tissue and liver of proteins essential for the maintenance of the nuclear-mitochondria crosstalk in neurons. In the developing world nutritional therapy may be superseded with relevance to xenobiotic induced mitochondrial apoptosis \hyperref[b61]{[104]} with accelerated synaptic plasticity defects and neurodegeneration. Activators of Sirt 1 such as leucine may be essential for mitochondrial biogenesis \hyperref[b62]{[105,}\hyperref[b64]{106]} and with stress disorders the apelinergic system defects [57] may lead to accelerated mitochondrial apoptosis with neuroendocrine disease. Interests in nutritional therapy include Sirt 1 activators such as pyrroloquinoline quinone, resveratroland rutin \hyperref[b65]{[107]}\hyperref[b66]{[108]}\hyperref[b67]{[109]}\hyperref[b68]{[110]} that specifically stimulate mitochondria biogenesisin the liver and brain compared with ochratoxin A \hyperref[b69]{[111]} that interferes with mitochondrial respiration. \section[{Conclusion}]{Conclusion}\par Interests in the early diagnosis of neuron senescence has become a major concern for many global communities with accelerated neurodegeneration involved with the metabolic syndrome and various chronic diseases. The mitochondria in neurons are sensitive to dysregulation with irreversible defects in these mitochondria that result in neuron apoptosis early in life. The plasma proteins such as Apelin, Angiotensin II, Gelsolin, Heat shock proteins (HSP 70, HSP 60), Thrombospondin 1 (TSP-1), Transforming growth factor beta (TGF beta), Tumour necrosis factor alpha (TNF alpha), Insulin like growth factor 1 (IGF-1), Fibroblast growth factor 21 (FGF21), GDF11, Adiponectin and Hepatocyte growth factor (HGF) should be measured early in life to determine mitochondrial damage in brain cells. The importance of the plasma profile is now relevant to assessment by nutritional therapy to reverse and halt neuron loss that is irreversible with relevance to the accelerated neurodegeneration and early nutritional regulation has become critical to the reversal of the global NAFLD, metabolic syndrome and chronic diseases. \section[{Volume XVI Issue II Version I}]{Volume XVI Issue II Version I}\begin{figure}[htbp] \noindent\textbf{} \par \begin{longtable}{} \end{longtable} \par \caption{\label{tab_0}}\end{figure} \begin{figure}[htbp] \noindent\textbf{} \par \begin{longtable}{P{0.5104333050127442\textwidth}P{0.3395666949872557\textwidth}} \multicolumn{2}{l}{Early Diagnosis of Neuron Mitochondrial Dysfunction May Reverse Global Metabolic and}\\ \multicolumn{2}{l}{Neurodegenerative Disease}\\ Crosstalk 54. Attané C., Foussal C., Le Gonidec S., Benani A., between circadian rhythmicity,\tabcellsep 41. Metcalfe A.M., Dixon R.M. and Radda G.K., (1997):\\ mitochondrial Daviaud D., et al., (2012): Apelin treatment dynamics and macrophage\tabcellsep Wild-type but not mutant p53 activates the\\ bactericidal activity. Immunology. 2014 Nov; 143(3): increases complete Fatty Acid oxidation,\tabcellsep hepatocyte growth factor/scatter factor promoter.\\ 490-7. mitochondrial oxidative capacity, and biogenesis in\tabcellsep Nucleic Acids Res; 25(5): 983-986.\\ 25. Langmesser S 1 , Albrecht U. Life time-circadian muscle of insulin-resistant mice. Diabetes; 61(2):\tabcellsep 42. Stein Y., Jacob A., Goldfinger N., Straussman R.\\ clocks, mitochondria and metabolism. Chronobiol 310-20.\tabcellsep andRotter V., (2016): Mutant p53 modulates the\\ Int. 2006; 23(1-2): 151-7. 55. Frier B.C., Williams D.B. and Wright D.C., (2009) The\tabcellsep signal of hepatocyte growth factor (HGF) to endow\\ 26. Hu F. and Liu F., (2011): Mitochondrial stress: a effects of apelin treatment on skeletal muscle\tabcellsep cancer cells with drug resistance. European Journal\\ bridge between mitochondrial dysfunction and mitochondrial content. Am J Physiol Regul Integr\tabcellsep of Cancer; 61(Supplement 1): S134.\\ metabolic diseases? Cell Signal; 23(10): 1528-33. Comp Physiol; 297(6): R1761-8.\tabcellsep 43. Xia S. andLaterra J., (2006): Hepatocyte growth\\ 27. Todorova V. and Blokland A., (2016): Mitochondria 56. Dikalov S.I. and Nazarewicz R.R., (2013):\tabcellsep factor increases mitochondrial mass in glioblastoma\\ and Synaptic Plasticity in the Mature and Aging Angiotensin II-induced production of mitochondrial\tabcellsep cells. Biochem Biophys Res Commun; 345(4):\\ Year 2016 ( D D D D ) A 58. Volume XVI Issue II Version I 28. Aguilar-Arnal L. and Sassone-Corsi P., (2015): Nervous System. Curr Neuropharmacol; 2016. [Epub ahead of print] Chromatin landscape and circadian dynamics: Spatial and temporal organization of clock transcription. Proc Natl Acad Sci U S A; 112(22): 6863-70. 29. Hirschey M.D., Shimazu T., Huang J.Y. and Verdin E., (2009): Acetylation of mitochondrial proteins. Methods Enzymol; 457: 137-47. 30. Tang B.L. (2016): Sirt1 and the Mitochondria. Mol Cells; 39(2): 87-95. 31. Rey G. andReddy A.B., (2013):Protein acetylation links the circadian clock to mitochondrial function. Proc Natl Acad Sci U S A; 110(9): 3210-1. 32. Anderson K.A. and Hirschey M.D., (2012): Mitochondrial protein acetylation regulates metabolism. Essays Biochem; 52: 23-35. 33. Sack M.N. andFinkel T., (2012)Mitochondrial metabolism, sirtuins, and aging. Cold Spring Harb Perspect Biol; 1:4(12). 34. Kil I.S., Ryu K.W., Lee S.K., Kim J.Y., Chu S.Y. et al., (2015): Circadian Oscillation of Sulfiredoxin in the Mitochondria. Mol Cell; 59(4): 651-63. 35. Brenmoehl J. and Hoeflich A., (2013): Dual control of mitochondrial biogenesis by sirtuin 1 and sirtuin 3. Mitochondrion. 13;6: 755-761. 36. Hirschey M.D., Shimazu T., Capra J.A., Pollard K.S. and Verdin E. (2011): SIRT1 and SIRT3 deacetylate homologous substrates: AceCS1, 2 and HMGCS1, 2. Aging (Albany NY); 3(6): 635-42. 37. Stephen T.L., Gupta-Agarwal S. andKittler J.T., (2014): Mitochondrial dynamics in astrocytes. Biochem Soc Trans; 42(5): 1302-10. 38. Cabezas R., El-Bachá R.S., González J. and Barreto G.E., (2012): Mitochondrial functions in astrocytes: Neuroprotective implications from oxidative damage by rotenone. Neurosci Res; 74 (2): 80-90. 39. Hayakawa K., Esposito E., Wang X., Terasaki Y., Liu Y., et al., (2016): Transfer of mitochondria from astrocytes to neurons after stroke. Nature; 535 (7613): 551-5. 40. Funakoshi H and Nakamura T., (2003): Hepatocyte reactive oxygen species: potential mechanisms and relevance for cardiovascular disease. Antioxid Redox Signal; 19(10): 1085-94. 57. Martins I.J., (2015): Nutritional diets accelerate amyloid beta metabolism and prevent the induction of chronic diseases and Alzheimer's disease. Photon ebooks. UBN: 015-A94510112017 Year 2016 D D D D ) ( A\tabcellsep 1358-64. 44. Tyndall S.J. and Walikonis R.S., (2007) Signaling by hepatocyte growth factor in neurons is induced by pharmacological stimulation of synaptic activity. Synapse; 61(4): 199-204. 45. Maina F. andKlein R., (1999): Hepatocyte growth factor, a versatile signal for developing neurons. Nat Neurosci; 2(3): 213-7. 46. Maina F., Hilton M.C., Andres R., Wyatt S., Klein R.,et al., (1998): Multiple roles for hepatocyte growth factor in sympathetic neuron development. Neuron; 20(5): 835-46. 47. Hamanoue M., Takemoto N., Matsumoto K., Nakamura T., Nakajima K. et al., (1996): Neurotrophic effect of hepatocyte growth factor on central nervous system neurons in vitro. J Neurosci Res; 43(5): 554-64. 48. Wong W.K., Cheung A.W., Yu S.W., Sha O. and Cho E.Y. (2014): Hepatocyte growth factor promotes long-term survival and axonal regeneration of retinal ganglion cells after optic nerve injury: comparison with CNTF and BDNF. CNS Neurosci Ther; 20(10): 916-29. 49. Watanabe T., Sakata Y., Matsubara S., Yamagishi T., Nagaike K., Kuwata T., et al., (2006): Changes in plasma levels of hepatocyte growth factor and its associated factors during pregnancy. J Obstet Gynaecol Res; 32(1): 10-4. 50. Chau M.D., Gao J., Yang Q., Wu Z. and Gromada J., (2010): Fibroblast growth factor 21 regulates energy metabolism by activating the AMPK-SIRT1-PGC-1alpha pathway. Proc Natl Acad Sci U S A; 107(28): 12553-8. 51. Suomalainen A., (2013): Fibroblast growth factor 21: a novel biomarker for human muscle-manifesting mitochondrial disorders. Expert Opin Med Diagn; 7(4): 313-7. 52. Davis R.L., Liang C., Edema-Hildebrand F., Riley C., Needham M., et al., (2013):Fibroblast growth factor 21 is a sensitive biomarker of mitochondrial disease. Neurology; 81(21): 1819-26. 53. Martins I.Year 2016 D D D D ) ( A\\ growth factor: from diagnosis to clinical\tabcellsep \\ applications. Clin Chim Acta; 327(1-2): 1-23.\tabcellsep \end{longtable} \par {\small\itshape [Note: J., (2016): Diet and Nutrition reverse Type 3 Diabetes and Accelerated Aging linked to Global chronic diseases. J Diab Res Ther; 2(2): 1-6. Volume XVI Issue II Version I © 2016 Global Journals Inc. (US)]} \caption{\label{tab_1}}\end{figure} \footnote{© 2 016 Global Journals Inc. (US)} \backmatter \subsection[{Acknowledgements}]{Acknowledgements} \begin{bibitemlist}{1} \bibitem[Oliva-Ramírez J 1 et al.]{b23}\label{b23} \textit{}, Oliva-Ramírez J 1 , M M Moreno-Altamirano , B Pineda-Olvera , P Cauich-Sánchez , F J Sánchez-García . \bibitem[Myotubes and Metab]{b63}\label{b63} \textit{}, . J Nutrit Myotubes , Metab . ID 239750. 2014. \bibitem[Qiao et al. ()]{b44}\label{b44} ‘Adiponectin increases skeletal muscle mitochondrial biogenesis by suppressing mitogenactivated protein kinase phosphatase-1’. L Qiao , B Kinney , H S Yoo , B Lee , J Schaack . \textit{Diabetes} 2012. 61 (6) p. . \bibitem[Gan et al. ()]{b43}\label{b43} ‘Adiponectin prevents reduction of lipid-induced mitochondrial biogenesis via AMPK/ACC2 pathway in chicken adipocyte’. L Gan , J Yan , Z Liu , M Feng , C Sun . \textit{J Cell Biochem} 2015. 116 (6) p. . \bibitem[Frazier et al. ()]{b46}\label{b46} ‘Age-dependent regulation of skeletal muscle mitochondria by the thrombospondin-1 receptor CD47’. E P Frazier , J S Isenberg , S Shiva , L Zhao , P Schlesinger . \textit{Matrix Biol} 2011. 30 (2) p. . \bibitem[Mattson and Magnus ()]{b5}\label{b5} ‘Ageing and neuronal vulnerability’. M P Mattson , T Magnus . \textit{Nat Rev Neurosci} 2006. 7 (4) p. . \bibitem[Hage-Sleiman et al. ()]{b51}\label{b51} ‘and Ceramide as Collaborators in the Stress Response’. R Hage-Sleiman , M O Esmerian , H Kobeissy , G Dbaibo . \textit{Int J Mol Sci} 2013. 14 (3) p. . \bibitem[Koczor et al. ()]{b14}\label{b14} ‘and Mitochondrial DNA, Their Role in Mitochondrial Homeostasis and Toxicity of Antiretrovirals’. C A Koczor , R C White , P Zhao , L Zhu , E Fields . \textit{Am J Pathol} 2012. 180 (6) p. . \bibitem[Martins ()]{b8}\label{b8} ‘Anti-Aging Genes Improve Appetite Regulation and Reverse Cell Senescence and Apoptosis in Global Populations’. I J Martins . \textit{Adv Aging Res} 2016. 5 p. . \bibitem[Martins ()]{b1}\label{b1} ‘Appetite Control with Relevance to Mitochondrial Biogenesis and Activation of Post-Prandial Lipid Metabolism in Obesity Linked Diabetes’. I J Martins . \textit{Ann. Obes. Disord} 2016. 1 (3) p. . \bibitem[Park et al. ()]{b15}\label{b15} ‘as guardian of the mitochondrial genome’. J-H Park , J Zhuang , J Li , P M Hwang . \textit{FEBS Letters} 2016. 590 (7) p. . \bibitem[Park et al. ()]{b32}\label{b32} ‘as guardian of the mitochondrial genome’. J-H Park , J Zhuang , J Li , P M Hwang . \textit{FEBS Letters} 2016. 590 (7) p. . \bibitem[Ricci et al. ()]{b3}\label{b3} ‘Astrocyte-neuron interactions in neurological disorders’. G Ricci , L Volpi , L Pasquali , L Petrozzi , G Siciliano . \textit{J Biol Phys} 2009. 2009. 35 (4) p. . \bibitem[Lane et al. ()]{b7}\label{b7} ‘Beyond amyloid: the future of therapeutics for Alzheimer's disease’. R F Lane , D W Shineman , J W Steele , L B Lee , H M Fillit . \textit{Adv Pharmacol} 2012. 64 p. . \bibitem[Sikora et al. ()]{b54}\label{b54} ‘Cellular senescence in ageing, age-related disease and longevity’. E Sikora , A Bielak-Zmijewska , G Mosieniak . \textit{Curr Vasc Pharmacol} 2014. 12 (5) p. . \bibitem[Neufeld-Cohen et al. ()]{b19}\label{b19} ‘Circadian control of oscillations in mitochondrial rate-limiting enzymes and nutrient utilization by PERIOD proteins’. A Neufeld-Cohen , M S Robles , R Aviram , G Manella , Y Adamovich . \textit{Proc Natl Acad Sci} 2016. 113 (12) p. . \bibitem[Gómez-Abellán et al. ()]{b41}\label{b41} ‘Circadian expression of adiponectin and its receptors in human adipose tissue’. P Gómez-Abellán , C Gómez-Santos , J A Madrid , F I Milagro , J Campion . \textit{Endocrinology} 2010. 151 (1) p. . \bibitem[Nilsson et al. ()]{b42}\label{b42} ‘Circadian variation in human cerebrospinal fluid production measured by magnetic resonance imaging’. C Nilsson , F Ståhlberg , C Thomsen , O Henriksen , M Herning . \textit{Am J Physiol} 1992. 262 (1) p. . (Pt 2) \bibitem[Yuzefovych et al. ()]{b56}\label{b56} ‘Different effects of oleate vs. palmitate on mitochondrial function, apoptosis, and insulin signaling in L6 skeletal muscle cells: role of oxidative stress’. L Yuzefovych , G Wilson , L Rachek . \textit{Am J Physiol Endocrinol Metab} 2010. 299 (6) p. . \bibitem[Penzo et al. ()]{b59}\label{b59} ‘Effects of fatty acids on mitochondria: implications for cell death’. D Penzo , C Tagliapietra , R Colonna , V Petronilli , P Bernardi . \textit{Biochim Biophys Acta} 2002. 1555 (1-3) p. . \bibitem[Safdar et al. ()]{b16}\label{b16} ‘Exercise increases mitochondrial PGC-1alpha content and promotes nuclearmitochondrial cross-talk to coordinate mitochondrial biogenesis’. A Safdar , J P Little , A J Stokl , B P Hettinga , M Akhtar . \textit{J Biol Chem} 2011. 286 (12) p. . \bibitem[Mironova et al. ()]{b57}\label{b57} ‘Formation of palmitic acid/Ca2+ complexes in the mitochondrial membrane: a possible role in the cyclosporininsensitive permeability transition’. G D Mironova , E Gritsenko , O Gateau-Roesch , C Levrat , A Agafonov . \textit{J Bioenerg Biomembr} 2004. 36 (2) p. . \bibitem[Vernadakis ()]{b4}\label{b4} ‘Glia-neuron intercommunications and synaptic plasticity’. A Vernadakis . \textit{Prog Neurobiol} 1996. 49 (3) p. . \bibitem[Wong et al. ()]{b24}\label{b24} ‘Hepatocyte growth factor promotes motor neuron survival and synergizes with ciliary neurotrophic factor’. V Wong , D J Glass , R Arriaga , G D Yancopoulos , R M Lindsay . \textit{J Biol Chem} 1997. 272 (8) p. . \bibitem[Higashida et al. ()]{b66}\label{b66} K Higashida , S H Kim , S R Jung , M Asaka , J O Holloszy . \textit{Effects of resveratrol and SIRT1 on PGC-1? activity and mitochondrial biogenesis: a reevaluation}, 2013. 11 p. e1001603. \bibitem[Russell et al. ()]{b55}\label{b55} ‘High glucoseinduced oxidative stress and mitochondrial dysfunction in neurons’. J W Russell , D Golovoy , A M Vincent , P Mahendru , J A Olzmann . \textit{FASEB J} 2002. 16 (13) p. . \bibitem[Martins ()]{b61}\label{b61} ‘Increased Risk for Obesity and Diabetes with Neurodegeneration in Developing Countries’. I J Martins . \textit{J Mol Genet Med} 2013. 1 (001) p. . \bibitem[Voloboueva et al. ()]{b13}\label{b13} ‘Inhibition of mitochondrial function in astrocytes: implications for neuroprotection’. L A Voloboueva , S W Suh , R A Swanson , R G Giffard . \textit{J Neurochem} 2007. 102 (4) p. . \bibitem[Sádaba et al. ()]{b33}\label{b33} ‘Insulin-like growth factor 1 (IGF-1) therapy: Mitochondrial dysfunction and diseases’. M C Sádaba , I Martín-Estal , J E Puche , I Castilla-Cortázar . \textit{Biochim Biophys Acta} 2016. 1862 (7) p. . \bibitem[Sunx and Zemel ()]{b64}\label{b64} ‘Leucine modulation of mitochondrial mass and oxygen consumption in skeletal muscle cells and adipocytes’. Sunx , M B Zemel . \textit{Nutr Metab} 2009. 6 p. 26. \bibitem[Liang et al. ()]{b62}\label{b62} C Liang , B J Curry , P L Brown , M B Zemel . \textit{Leucine Modulates Mitochondrial Biogenesis and SIRT1-AMPK Signaling}, 2014. p. . \bibitem[Martins and Creegan ()]{b2}\label{b2} \textit{Links between Insulin Resistance, Lipoprotein Metabolism and Amyloidosis in Alzheimer's Disease. Health}, I J Martins , R Creegan . 2014. 6 p. . \bibitem[Lee and Wei ()]{b12}\label{b12} ‘Mitochondria and aging’. H C Lee , Y H Wei . \textit{Adv Exp Med Biol} 2012. 942 p. . \bibitem[Ben-Shachar and Laifenfeld ()]{b22}\label{b22} ‘Mitochondria, synaptic plasticity, and schizophrenia’. D Ben-Shachar , D Laifenfeld . \textit{Int Rev Neurobiol} 2004. 59 p. . \bibitem[Roué et al. ()]{b45}\label{b45} ‘Mitochondrial dysfunction in CD47-mediated caspase-independent cell death: ROS production in the absence of cytochrome c and AIF release’. G Roué , N Bitton , V J Yuste , T Montange , M Rubio . \textit{Biochimie} 2003. 85 (8) p. . \bibitem[Jain et al. ()]{b37}\label{b37} ‘Mitochondrial reactive oxygen species regulate transforming growth factor-? signaling’. M Jain , S Rivera , E A Monclus , L Synenki , A Zirk . \textit{J Biol Chem} 2013. 288 (2) p. . \bibitem[Sheng ()]{b21}\label{b21} ‘Mitochondrial trafficking and anchoring in neurons: New insight and implications’. Z H Sheng . \textit{J Cell Biol} 2014. 204 (7) p. . \bibitem[Sheng and Cai ()]{b20}\label{b20} ‘Mitochondrial transport in neurons: impact on synaptic homeostasis and neurodegeneration’. Z H Sheng , Q Cai . \textit{Nat Rev Neurosci} 2012. 13 (2) p. . \bibitem[Bina and Rusak ()]{b28}\label{b28} ‘Nerve growth factor phase shifts circadian activity rhythms in Syrian hamsters’. K G Bina , B Rusak . \textit{Neurosci Lett} 1996. 206 (2-3) p. . \bibitem[Brynczka and Merrick ()]{b25}\label{b25} ‘Nerve growth factor potentiates p53 DNA binding but inhibits nitric oxide-induced apoptosis in neuronal PC12 cells’. C Brynczka , B A Merrick . \textit{Neurochem Res} 2007. 32 (9) p. . \bibitem[Zhou et al. ()]{b26}\label{b26} \textit{Nerve growth factor receptor negates the tumor suppressor p53 as a feedback regulator}, X Zhou , Q Hao , P Liao , S Luo , M Zhang . 2016. p. e15099. \bibitem[Pizzio et al. ()]{b29}\label{b29} ‘Nerve growth factorinduced circadian phase shifts and MAP kinase activation in the hamster suprachiasmatic nuclei’. G A Pizzio , E C Hainich , S A Plano , M R Ralph , D A Golombek . \textit{European J Neurosci} 2005. 22 (3) p. . \bibitem[Eisenberg and Burgess ()]{b0}\label{b0} ‘Nutrition Education in an Era of Global Obesity and Diabetes: Thinking Outside the Box’. D M Eisenberg , J D Burgess . \textit{Acad. Med} 2015. 90 (7) p. . \bibitem[Kwon and Querfurth ()]{b58}\label{b58} ‘Opposite effects of saturated and unsaturated free fatty acids on intracellular signaling and metabolism in neuronal cells’. B Kwon , H W Querfurth . \textit{Inflamm Cell Signal} 2014. 1 p. e200. \bibitem[Aquilano et al. ()]{b18}\label{b18} ‘Orchestrates the PGC-1?-Mediated Antioxidant Response Upon Mild Redox and Metabolic Imbalance’. K Aquilano , S Baldelli , B Pagliei , S M Cannata , G Rotilio , M R Ciriolo . \textit{Antioxid Redox Signal} 2013. 18 (4) p. . \bibitem[Martins ()]{b69}\label{b69} ‘Overnutrition Determines LPS Regulation of Mycotoxin Induced Neurotoxicity in Neurodegenerative Diseases’. I J Martins . \textit{Int J Mol Sci} 2015. 16 (12) p. . \bibitem[Dbaibo et al. ()]{b52}\label{b52} ‘p53-dependent ceramide response to genotoxic stress’. G S Dbaibo , M Y Pushkareva , R A Rachid , N Alter , M J Smyth . \textit{J Clin Invest} 1998. 102 (2) p. . \bibitem[Hsiao et al. ()]{b60}\label{b60} ‘Palmitic acid-induced neuron cell cycle G2/M arrest and endoplasmic reticular stress through protein palmitoylation in SH-SY5Y human neuroblastoma cells’. Y H Hsiao , C I Lin , H Liao , Y H Chen , S H Lin . \textit{Int J Mol Sci} 2014. 15 (11) p. . \bibitem[Sen et al. ()]{b17}\label{b17} ‘PGC-1?, a key modulator of p53, promotes cell survival upon metabolic stress’. N Sen , Y K Satija , S Das . \textit{Mol Cell} 2011. 44 (4) p. . \bibitem[Jang et al. ()]{b30}\label{b30} ‘Plasma and saliva levels of nerve growth factor and neuropeptides in chronic migraine patients’. M U Jang , J W Park , H S Kho , S C Chung , J W Chung . \textit{Oral Dis} 2011. 17 (2) p. . \bibitem[Presentation: Antiaging genes regulate post-prandial lipid metabolism with relevance to appetite, chronic disease and neurodegeneration nd International Conference and Expo on Lipids: Metabolism Nutrition and Health ()]{b10}\label{b10} ‘Presentation: Antiaging genes regulate post-prandial lipid metabolism with relevance to appetite, chronic disease and neurodegeneration’. \url{https://www.researchgate.net/profile/Ian\textunderscore Martins2Article} \textit{nd International Conference and Expo on Lipids: Metabolism Nutrition and Health}, October 03-05, 2016. (Appetite Control with Relevance to Mitochondrial Biogenesis and) \bibitem[Zhang et al. ()]{b65}\label{b65} ‘Pyrroloquinoline quinone increases the expression and activity of Sirt1 and -3 genes in HepG2 cells’. J Zhang , S Meruvu , Y S Bedi , J Chau , A Arguelles . \textit{Nutr Res} 2015. 35 (9) p. . \bibitem[Emanuele et al. ()]{b31}\label{b31} ‘Raised plasma nerve growth factor levels associated with early-stage romantic love’. E Emanuele , P Politi , M Bianchi , P Minoretti , M Bertona . \textit{Psychoneuroendocrinology} 2006. 31 (3) p. . \bibitem[Doll et al. ()]{b36}\label{b36} ‘Rapid mitochondrial dysfunction mediates TNF-alpha-induced neurotoxicity’. D N Doll , S L Rellick , T L Barr , X Ren , J W Simpkins . \textit{J Neurochem} 2015. 132 (4) p. . \bibitem[Sinha et al. ()]{b34}\label{b34} ‘Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle’. M Sinha , Y C Jang , J Oh , D Khong , E Y Wu . \textit{Science} 2014. 344 (6184) p. . \bibitem[Gulbins et al. ()]{b11}\label{b11} ‘Role of mitochondria in apoptosis’. E Gulbins , S Dreschers , J Bock . \textit{Exp Physiol} 2003. 88 (1) p. . \bibitem[Su et al. ()]{b68}\label{b68} ‘Rutin, a flavonoid and principal component of saussurea involucrata, attenuates physical fatigue in a forced swimming mouse model’. K Y Su , C Y Yu , Y W Chen , Y T Huang , C T Chen . \textit{Int J Med Sci} 2014. 11 (5) p. . \bibitem[Seo et al. ()]{b67}\label{b67} S Seo , M S Lee , E Chang , Y Shin , S Oh . \textit{Rutin Increases Muscle Mitochondrial Biogenesis with AMPK Activation in High-Fat Diet-Induced Obese Rats}, 2015. 7 p. . \bibitem[Yamamoto et al. ()]{b35}\label{b35} ‘SIRT1 regulates adaptive response of the growth hormone--insulin-like growth factor-I axis under fasting conditions in liver’. M Yamamoto , G Iguchi , H Fukuoka , K Suda , H Bando . \textit{Proc Natl Acad Sci} 2013. 110 (37) p. . \bibitem[Shen et al. ()]{b53}\label{b53} ‘Sphingosine 1-phosphate (S1P) promotes mitochondrial biogenesis in Hep G2 cells by activating Peroxisome proliferator-activated receptor ? coactivator 1? (PGC-1?)’. Z Shen , C Liu , P Liu , J Zhao , W Xu . \textit{Cell Stress Chaperones} 2014. 19 (4) p. . \bibitem[Barnea et al. ()]{b40}\label{b40} ‘The circadian clock machinery controls adiponectin expression’. M Barnea , N Chapnik , Y Genzer , O Froy . \textit{Mol Cell Endocrinol} 2015. 399 p. . \bibitem[Tedeschi and Giovanni ()]{b27}\label{b27} ‘The nonapoptotic role of p53 in neuronal biology: enlightening the dark side of the moon’. A Tedeschi , Di Giovanni , S . \textit{EMBO Rep} 2009. 10 (6) p. . \bibitem[Martins ()]{b6}\label{b6} ‘The Role of Clinical Proteomics, Lipidomics, and Genomics in the Diagnosis of Alzheimer's Disease’. I J Martins . \textit{Proteomes} 2016. 4 (2) p. . \bibitem[Grossfeld et al. ()]{b47}\label{b47} ‘Thrombospondin-1 expression in bladder cancer: association with p53 alterations, tumor angiogenesis, and tumor progression’. G D Grossfeld , D A Ginsberg , J P Stein , B H Bochner , D Esrig . \textit{J Natl Cancer Inst} 1997. 89 (3) p. . \bibitem[Alvarez et al. ()]{b48}\label{b48} ‘Thrombospondin-1 expression in epithelial ovarian carcinoma: association with p53 status, tumor angiogenesis, and survival in platinum-treated patients’. A A Alvarez , J R Axelrod , R S Whitaker , P D Isner , R C Bentley . \textit{Gynecol Oncol} 2001. 82 (2) p. . \bibitem[Baek et al. ()]{b50}\label{b50} ‘Thrombospondin-1 mediates oncogenic Ras-induced senescence in premalignant lung tumors’. K H Baek , D Bhang , A Zaslavsky , L C Wang , A Vachani . \textit{J Clin Invest} 2013. 123 (10) p. . \bibitem[Kaur et al. ()]{b49}\label{b49} \textit{Thrombospondin-1 Signaling through CD47 Inhibits Self-renewal by Regulating c-Myc and Other Stem Cell Transcription Factors Scientific Reports}, S Kaur , D R Soto-Pantoja , E V Stein , C Liu , A G Elkahloun . 2013. 1673. 3 p. . \bibitem[Gast et al. ()]{b38}\label{b38} ‘Transforming growth factor-beta inhibits the expression of clock genes’. H Gast , S Gordic , S Petrzilka , M Lopez , A Müller . \textit{Ann N Y Acad Sci} 2012. 1261 p. . \bibitem[Lopez et al. ()]{b39}\label{b39} ‘Tumor necrosis factor and transforming growth factor ? regulate clock genes by controlling the expression of the cold inducible RNA-binding protein (CIRBP)’. M Lopez , D Meier , A Müller , P Franken , J Fujita . \textit{J Biol Chem} 2014. 289 (5) p. . \bibitem[Martins ()]{b9}\label{b9} ‘Unhealthy Nutrigenomic Diets Accelerate NAFLD and Adiposity in Global communities’. I J Martins . \textit{J Mol Genet Med} 2015. 9 (1) p. . \end{bibitemlist} \end{document}