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

#### **2.1 Phosphorous (P)**

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**.

#### **2.2 Potassium (K)**

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

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

#### **Figure 2.**

*Role of mineral elements in disease prevention. a: Role of phosphorous in bone mineralisation, b: Potassium involvement in muscle contraction, c: Calcium in bone calcification, d: Magnesium in protection of neuron degeneration, e: Sulphur in prevention of muscle pains and joint pains, f: Fluorine in preventation of dental caries, g: Iodine in thyroid hormones, h: Iron in haemoglobin synthesis, i: Sodium in heart function, j: Zinc in immunity.*

#### **Figure 3.**

*Deficiency disease leads to aging through disturbed signalling pathway. Mineral deficiencies were shown in parenthesis. Ca: Calcium, I: Iodine, Mg: Magnesium, P: Phosphorous, Na: Sodium, S: Sulphur, Zn: Zinc, F: Fluorine, K: potassium, Fe: Iron. TSH: Thyroid stimulating hormone, Nrf 2-nucleoid erythroid receptor factor 2. FGF-fibroblast growth factor, SIRT1; Sirtuins 1, mTORC1: mammalian target of rapamycin complex 1, NF*κ*B: Natural factor kappa beta, IL-6: interleukin 6, TGF-tumor growth factor, MAPK-mitogen activated protein kinase, Wnt-Wingless-related integration site.*

balance, regulation of acid–base balance, required for transmission of nerve impulse, and necessary for biosynthesis of proteins. Plasma levels are 3.4-5 mEq/L absorbed through intestine excreted in form of urine. Deficiency diseases include muscle weakness, mental confusion. Potassium ion present on the cells as potassium ion channels and various types of potassium ion channels include ATP-sensitive K channels (KATP), voltage-dependent K channels (Kv), Ca2+ − and voltage-dependent K channels (BKCa), inward rectifier K channels (Kir), and tandem two-pore K channels (K2P) their activity varies in different types of diseases [39]. Potassium as

**33**

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

known to play a role in Na + -K+ ATPase for effective muscle contraction [40] and motor regulation is by ATP driven potassium channels [41]. ATP driven potassium channel deficiency affected resting tension of skeletal muscle [42] deficiency of potassium ions alters sodium potassium pump of skeletal muscle and augments its contraction in ageing [43]. According to previous reports, high potassium levels depolarizes smooth muscle cells that opens up voltage gated calcium channels resulting in entry of calcium ions inside the cells thereby leading to activation of smooth muscle contraction [44] The role of potassium in muscle contraction shown in **Figure 2b.** It had reported that activation of mTORC1 signalling correlated with decline in muscle mass [45, 46] activated mTORC1induces oxidative stress that leads to protein degradation, autophagy and necrosis showing an aged phenotype [47]. The signalling pathway connecting potassium deficiency and ageing shown in

Biological availability of calcium is green leafy vegetables, nuts, seafood, cereals etc. Cow's milk is rich source of calcium and required daily about 0.8-1.0 g/day. Calcium plays an important role in development of bones, muscle contraction, blood coagulation, nerve transmission, membrane integrity, activation of enzymes, intracellular messenger, contact inhibition, nerve excitability, skeletal muscle integrity and maintenance, and cardiac tone. Factors promoting calcium absorption include low pH, parathyroid hormone, vitamin D, lactose. Most of blood calcium is in plasma and ranges about 9-11 mg/dl. Factors regulating plasma calcium include calcitriol, parathyroid hormone, and calcitonin. Calcium excreted mostly through intestine and partly by kidneys. Deficiency of calcium leads to hypocalcemia and shown signs such as fragility of bone, muscle cramping, and dry skin. Deficiency diseases include rickets osteomalacia, osteoporosis. Evidences reveal that calcium is involved in bone calcification where osteoblasts secrete collagen as ground substance and polymerises it then osteoblast entrap osteoid and calcium salts precipitates as non-crystalline amorphous substance. Reabsorption and reprecipitation of hydroxyapatite crystals makes bone calcified. Existing reports evidence that stimulation of PGC-1α signalling regulate osteoporosis and ageing [48]. The role of calcium in osteoblast calcification shown in **Figure 2c**. Recent reports reveal that Wnt, MAPK, oestrogen pathways are targets for osteoporosis and ageing, it had shown that Wnt pathway responsible for production of sclerotin is dysregulated and MAPK pathway altered in osteoporosis [49]. The signalling pathway connecting

Sources of this mineral include milk, meat, fruits, and cereals. Biochemical functions include formation of bone, teeth, neuromuscular irritability, and cofactor for enzymes (kinases). Daily intake is 300-350 mg, serum concentration is 2-3 mg/dl and deficiency leads to convulsions, neuromuscular irritation, uraemia, and rickets. Magnesium absorption occurs in intestine alcohol inhibits it whereas parathormone enhances it. Causes of magnesium deficiency include alcohol abuse, poorly controlled diabetes, excessive or chronic vomiting and/or diarrhoea. Research on neurodegenerative diseases reveal magnesium had neuroprotective role by inhibiting influx of amyloid β from blood and promote its clearance [50] furthermore it attenuates impairment in long-term potentiation and impaired recruitment of synaptic proteins through activation of PI3K/Akt and inhibition of GSK3 β thereby reducing neuronal damage [51]. To date several reports indicate that Nrf-2

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

calcium deficiency and ageing shown in **Figure 3**.

**2.4 Magnesium (Mg)**

**Figure 3**.

**2.3 Calcium (Ca)**

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

known to play a role in Na + -K+ ATPase for effective muscle contraction [40] and motor regulation is by ATP driven potassium channels [41]. ATP driven potassium channel deficiency affected resting tension of skeletal muscle [42] deficiency of potassium ions alters sodium potassium pump of skeletal muscle and augments its contraction in ageing [43]. According to previous reports, high potassium levels depolarizes smooth muscle cells that opens up voltage gated calcium channels resulting in entry of calcium ions inside the cells thereby leading to activation of smooth muscle contraction [44] The role of potassium in muscle contraction shown in **Figure 2b.** It had reported that activation of mTORC1 signalling correlated with decline in muscle mass [45, 46] activated mTORC1induces oxidative stress that leads to protein degradation, autophagy and necrosis showing an aged phenotype [47]. The signalling pathway connecting potassium deficiency and ageing shown in **Figure 3**.

### **2.3 Calcium (Ca)**

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

balance, regulation of acid–base balance, required for transmission of nerve impulse, and necessary for biosynthesis of proteins. Plasma levels are 3.4-5 mEq/L absorbed through intestine excreted in form of urine. Deficiency diseases include muscle weakness, mental confusion. Potassium ion present on the cells as potassium ion channels and various types of potassium ion channels include ATP-sensitive K channels (KATP), voltage-dependent K channels (Kv), Ca2+ − and voltage-dependent K channels (BKCa), inward rectifier K channels (Kir), and tandem two-pore K channels (K2P) their activity varies in different types of diseases [39]. Potassium as

*Deficiency disease leads to aging through disturbed signalling pathway. Mineral deficiencies were shown in parenthesis. Ca: Calcium, I: Iodine, Mg: Magnesium, P: Phosphorous, Na: Sodium, S: Sulphur, Zn: Zinc, F: Fluorine, K: potassium, Fe: Iron. TSH: Thyroid stimulating hormone, Nrf 2-nucleoid erythroid receptor factor 2. FGF-fibroblast growth factor, SIRT1; Sirtuins 1, mTORC1: mammalian target of rapamycin complex 1, NF*κ*B: Natural factor kappa beta, IL-6: interleukin 6, TGF-tumor growth factor, MAPK-mitogen activated* 

*Role of mineral elements in disease prevention. a: Role of phosphorous in bone mineralisation, b: Potassium involvement in muscle contraction, c: Calcium in bone calcification, d: Magnesium in protection of neuron degeneration, e: Sulphur in prevention of muscle pains and joint pains, f: Fluorine in preventation of dental caries, g: Iodine in thyroid hormones, h: Iron in haemoglobin synthesis, i: Sodium in heart function, j: Zinc in* 

**32**

**Figure 2.**

*immunity.*

**Figure 3.**

*protein kinase, Wnt-Wingless-related integration site.*

Biological availability of calcium is green leafy vegetables, nuts, seafood, cereals etc. Cow's milk is rich source of calcium and required daily about 0.8-1.0 g/day. Calcium plays an important role in development of bones, muscle contraction, blood coagulation, nerve transmission, membrane integrity, activation of enzymes, intracellular messenger, contact inhibition, nerve excitability, skeletal muscle integrity and maintenance, and cardiac tone. Factors promoting calcium absorption include low pH, parathyroid hormone, vitamin D, lactose. Most of blood calcium is in plasma and ranges about 9-11 mg/dl. Factors regulating plasma calcium include calcitriol, parathyroid hormone, and calcitonin. Calcium excreted mostly through intestine and partly by kidneys. Deficiency of calcium leads to hypocalcemia and shown signs such as fragility of bone, muscle cramping, and dry skin. Deficiency diseases include rickets osteomalacia, osteoporosis. Evidences reveal that calcium is involved in bone calcification where osteoblasts secrete collagen as ground substance and polymerises it then osteoblast entrap osteoid and calcium salts precipitates as non-crystalline amorphous substance. Reabsorption and reprecipitation of hydroxyapatite crystals makes bone calcified. Existing reports evidence that stimulation of PGC-1α signalling regulate osteoporosis and ageing [48]. The role of calcium in osteoblast calcification shown in **Figure 2c**. Recent reports reveal that Wnt, MAPK, oestrogen pathways are targets for osteoporosis and ageing, it had shown that Wnt pathway responsible for production of sclerotin is dysregulated and MAPK pathway altered in osteoporosis [49]. The signalling pathway connecting calcium deficiency and ageing shown in **Figure 3**.
