**1. Introduction**

A regulated diet with all the constituents consumed in appropriate way maintains cell homeostasis and keeps the body under physiological state that are essential for cellular demands. A number of factor contribute to body function such as biomolecules, vitamins, minerals, and hormones etc.….of these minerals gain utmost importance due to availability inside the cell is low but shows a major effects even small change in concentration. Minerals perform wide variety of functions, which are essential for existence of organism. Some of them form integral components, some as cofactors, and some as essential components of enzymes. The existence of these minerals as part of enzymes helps to play a role in metabolism of molecules

consumed through diet and maintain cell homeostasis. Some of the minerals acts in concert with aid of hormones according to their need in specific organelle. Minerals either in part or in combination with vitamins shows major functions required for the cell and their deficiencies shows adverse side effects although not hereditary. Minerals classified according to the need includes major (phosphorous (P), potassium (K), calcium (Ca), magnesium (Mg), sulphur (S)), minor/trace/ rare (Boron (B), chlorine (Cl), chromium (Cr), fluoride (F), iodine (I), iron (Fe), manganese (Mn), molybdenum (Mo), nickel (Ni), selenium (Se), sodium (Na), vanadium (V) and zinc (Zn)). In this chapter a detailed explanation of selected minerals about their importance as a source requirement, uptake and transport mechanism, toxicity and tolerance mechanism, taken as means of measurement for determining their beneficial effects to study in detail about the specific role in metabolism their mechanism of action and deficiency diseases associated with reduced life span had described.

Decline of physiological functions leading to senescence of cells with arrest at G1 phase is characteristic feature of ageing [1]. At cellular level senescence was caused due to several factors such as oxidative stress, mitochondrial dysfunction, inflammation, autophagy deregulation, telomere shortening [2, 3]. Cells senesce either due to continuous replication or due to stress induction thereby activating p16, p53 pathways and phosphorylation of Rb protein [4] leading to inflammatory condition with high lysosomal β-galactosidase activity [5–7]. As cells continuously, divide chromosomes containing telomere with repeated nucleotides region gets shortened [8] leads to replicative senescence [9] and result in ageing. In humans, the repeated sequence at telomere region is TTAGGG [10]. Cells capable of replicating continuously express telomerase for replication of telomere ends of chromosome, which had tendency to reverse ageing process and used as targeted approach [2]. Increased ROS production due to stress apart from normal cellular homeostasis as a compensatory mechanism aggravates ageing phenomenon. Free-radical theory proposes ROS leads to oxidative damage and contributes to plays a role in the ageing process [11]. First call to increased ROS levels inside the cells is activation of survival pathways, which further leads to apoptosis due to failure of antioxidant system to defence against ROS that ultimately leads to cell death [12, 13]. Several factors were responsible for production of ROS that disturbs balance between cell survival and cell death through increased redox potential towards pro-inflammatory state and connects oxidative stress, inflammation and ageing [14–16]. The release of pro-inflammatory agents inside the senescent cells include TNF-α, IL-6, IL-1β [17] regulated by transcription factors such as AP-1, NFκB [18]. The activation of AP-1, NFκB requires kinases such as ERK, JNK, p38MAPK, PI3K [19] and leads to expression of target proteins such as MMP9, ICAM-1, iNOS, COX-2 [20–22]. Mitochondria apart from playing a role in oxidative phosphorylation system it also plays a role in apoptosis, metabolism, innate immunity and ageing [23–25]. Mitochondrial regulation occurs through PGC-1 (α & β) that responds to NAD+ levels inside the cell [26, 27] and in response to SIRT1 regulation occurs by HIF-1α independent of PGC-1 [28]. In ageing NAD+ levels decreases without loss of SIRT1 but downregulates it [29]. One of the contributing factor for cell survival under stress conditions is autophagy [30]. Autophagy is downregulated under nutrient rich conditions through mTOR protein [31] and stimulated through AMPK by phosphorylating mTOR (inactivation) ultimately activating ULK-1 [32]. Reports reveal autophagy deregulates due to overexpression of mTOR [33, 34] in ageing. Several Genetic events (mTOR, TGFβ), Molecular events (oxidative stress, autophagy) also contribute to ageing phenomenon. A summary of factors responsible for cellular ageing were shown in **Figure 1**.

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**2.2 Potassium (K)**

*Mineral Deficiencies: A Root Cause for Reduced Longevity in Mammals*

**2. Deficiency of major mineral elements and lifespan**

Phosphorous is mostly present in meat, fish, eggs, and milk and dietary intake is 0.8-1.0 g/day. Phosphorus is essential for the formation of healthy bones, part of buffer system and component of DNA and RNA. Functions of phosphorous include formation of high-energy phosphates, nucleic acids, nucleotide coenzymes. Activation of enzymes require phosphate moiety and found in cell walls. Phosphorus deficiency include rickets, osteomalacia observed mostly in cases of malnutrition, anorexic individuals, or alcoholics. Symptoms are poor appetite, anxiety, and irritability. Phosphate absorption occurs in jejunum calcitriol, low pH favours their absorption while phytate reduces its absorption. Serum phosphate level is about 3-4 mg/dl and reduced in renal rickets, vitamin D deficient rickets and in diabetes mellitus. Phosphate excreted by kidney in the form of urine. Phosphate is mainly involved in mineralisation of the bone from chondrocytes and osteoblast. The process of mineralisation begins with hydroxyapatite formation from calcium (Ca + 2) and inorganic phosphate. Calcium incorporated through annexin calcium channel here as inorganic phosphate from type III sodium inorganic phosphate transporter and from PHOSPHO1. Hydroxyapatite penetrate the matrix vesicle and elongate due to tissue non-specific alkaline phosphatase (TNAP) and deposit in collagen fibre spaces [35]. The role of phosphorous in bone mineralisation shown in **Figure 2a**. Osteomalacia resulting from hypophosphatemia occurs through fibroblast growth factor signalling (FGF) [36] that links with ageing process [37]. Reduced phosphate levels inside the cell leads to increased FGF 23 levels in the serum and acts by inhibiting calcitriol, PTH, 1α-hydroxylase and stimulating 24-hydroxylase [38]. The signalling pathway connecting phosphorous deficiency and ageing shown in **Figure 3**.

*Factors responsible for aging: Different factors enhances process of aging includes autophagy, oxidative stress, shortening of telomere, caloric restriction, proteostasis, inflammation, mitochondrial dysfunction and* 

Potassium is principal intracellular cation required daily about 3-4 g that is present majorly in banana, orange, potato, chicken, and liver. It helps regulate fluid balance, nerve signals and muscle contractions and beneficial aspects include reduction in blood pressure, water retention; prevention of kidney stones, osteoporosis, and protection against strokes. It functions to maintain intracellular osmotic

**2.1 Phosphorous (P)**

**Figure 1.**

*DNA damage.*

*DOI: http://dx.doi.org/10.5772/intechopen.94276*

*Mineral Deficiencies: A Root Cause for Reduced Longevity in Mammals DOI: http://dx.doi.org/10.5772/intechopen.94276*

#### **Figure 1.**

*Mineral Deficiencies - Electrolyte Disturbances, Genes, Diet and Disease Interface*

reduced life span had described.

consumed through diet and maintain cell homeostasis. Some of the minerals acts in concert with aid of hormones according to their need in specific organelle. Minerals either in part or in combination with vitamins shows major functions required for the cell and their deficiencies shows adverse side effects although not hereditary. Minerals classified according to the need includes major (phosphorous (P), potassium (K), calcium (Ca), magnesium (Mg), sulphur (S)), minor/trace/ rare (Boron (B), chlorine (Cl), chromium (Cr), fluoride (F), iodine (I), iron (Fe), manganese (Mn), molybdenum (Mo), nickel (Ni), selenium (Se), sodium (Na), vanadium (V) and zinc (Zn)). In this chapter a detailed explanation of selected minerals about their importance as a source requirement, uptake and transport mechanism, toxicity and tolerance mechanism, taken as means of measurement for determining their beneficial effects to study in detail about the specific role in metabolism their mechanism of action and deficiency diseases associated with

Decline of physiological functions leading to senescence of cells with arrest at G1 phase is characteristic feature of ageing [1]. At cellular level senescence was caused due to several factors such as oxidative stress, mitochondrial dysfunction, inflammation, autophagy deregulation, telomere shortening [2, 3]. Cells senesce either due to continuous replication or due to stress induction thereby activating p16, p53 pathways and phosphorylation of Rb protein [4] leading to inflammatory condition with high lysosomal β-galactosidase activity [5–7]. As cells continuously, divide chromosomes containing telomere with repeated nucleotides region gets shortened [8] leads to replicative senescence [9] and result in ageing. In humans, the repeated sequence at telomere region is TTAGGG [10]. Cells capable of replicating continuously express telomerase for replication of telomere ends of chromosome, which had tendency to reverse ageing process and used as targeted approach [2]. Increased ROS production due to stress apart from normal cellular homeostasis as a compensatory mechanism aggravates ageing phenomenon. Free-radical theory proposes ROS leads to oxidative damage and contributes to plays a role in the ageing process [11]. First call to increased ROS levels inside the cells is activation of survival pathways, which further leads to apoptosis due to failure of antioxidant system to defence against ROS that ultimately leads to cell death [12, 13]. Several factors were responsible for production of ROS that disturbs balance between cell survival and cell death through increased redox potential towards pro-inflammatory state and connects oxidative stress, inflammation and ageing [14–16]. The release of pro-inflammatory agents inside the senescent cells include TNF-α, IL-6, IL-1β [17] regulated by transcription factors such as AP-1, NFκB [18]. The activation of AP-1, NFκB requires kinases such as ERK, JNK, p38MAPK, PI3K [19] and leads to expression of target proteins such as MMP9, ICAM-1, iNOS, COX-2 [20–22]. Mitochondria apart from playing a role in oxidative phosphorylation system it also plays a role in apoptosis, metabolism, innate immunity and ageing [23–25]. Mitochondrial regulation occurs through PGC-1 (α & β) that responds to NAD+ levels inside the cell [26, 27] and in response to SIRT1 regulation occurs by HIF-1α independent of PGC-1 [28]. In ageing NAD+ levels decreases without loss of SIRT1 but downregulates it [29]. One of the contributing factor for cell survival under stress conditions is autophagy [30]. Autophagy is downregulated under nutrient rich conditions through mTOR protein [31] and stimulated through AMPK by phosphorylating mTOR (inactivation) ultimately activating ULK-1 [32]. Reports reveal autophagy deregulates due to overexpression of mTOR [33, 34] in ageing. Several Genetic events (mTOR, TGFβ), Molecular events (oxidative stress, autophagy) also contribute to ageing phenomenon. A summary of factors responsible for cellular ageing

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were shown in **Figure 1**.

*Factors responsible for aging: Different factors enhances process of aging includes autophagy, oxidative stress, shortening of telomere, caloric restriction, proteostasis, inflammation, mitochondrial dysfunction and DNA damage.*
