**4. Conclusion**

Minerals play an important role in daily life ranging from nuts to leafy vegetables. Minerals mainly function as cofactors along with enzymes to show their metabolic effect. Minerals form holoenzymes in metabolism of biomolecules and help in cellular vital process for cell survival. In their absence, the show some deficient metabolic effects and required in small amounts to function effectively. Intake


*Abbreviations: FGF-fibroblast growth factor, SOD-superoxide dismutase, NOX-NADPH oxidase, MT-metallothionin, T3-tri iodothyronine, T4-tetra iodothyronine, PI3K-Phosphatidyl inositol 3 kinase, MAPKmitogen activated protein kinase, Wnt-Wingless-related integration site, Nrf 2-nucleoid erythroid receptor factor 2, TSH-thyroid stimulating hormone, TGF-tumour growth factor, SIRT 1-sirutin1, mTORC1-mammalian target of rapamycin complex 1, NFkB-natural factor kappa beta.*

**39**

**Appendices**

Ca calcium I iodine Mg magnesium P phosphorous Na sodium S sulphur Zn zinc F Fluorine K potassium Fe iron

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

varies from infants to adults, gender excess amounts shows hyper forms, and low amounts leads to hypo effects. Mineral deficiencies mostly show aged phenotype and age related diseases have mineral deficiencies. In their absence cell, survival pathways are mostly non-functional and leads to decreased metabolic function that is characterised by aged phenotype. Minerals classified mostly upon their requirement as 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)). A selected mineral with their function importance in mammals have been described in detail in which Phosphorous (P), Potassium (K), Calcium (Ca), Magnesium (Mg), Sulphur (S),

nism of action and its diseased mechanism associated with ageing. Phosphorous is involved in bone mineralisation from osteocyte through hydroxyl apatite formation and deficiency leads to osteomalacia that related to ageing through increased fibroblast growth factor signalling. Potassium is involved in muscle contraction and its deficiency leads to muscle weakness and shows aged phenotype through enhanced mTORC1 signalling. Calcium is involved in bone calcification through hydroxyl apatite crystals its deficiency leads to bone disorders shows aged phenotype through dysregulated Wnt, MAPK pathway. Magnesium is involved in protection of neuron from degeneration through inhibition of GSK3β signalling and hyper activation of PI3K, Akt signalling and shows aged phenotype through dysregulated Nrf 2 pathway. Sulphur is involved in prevention of muscle pains and joint pains by reducing inflammation by scavenging free radicals its deficiency leads to muscle fatigue shows aged phenotype through reduced redox signalling. Fluorine is involved protection of enamel layer by remineralisation, crystallisation of dentine and enhancement in acid resistance its deficiency leads to dental caries which is also an aged phenotype due to disturbed KLF4pathway. Iodine is necessary for thyroid gland for production of thyroid hormones deficiency of it leads to goitre that is characterised by thyroid gland enlargement seen mostly in aged people or people taking iodine deficient diets that occurs through reduced TSH signalling. Iron is necessary for body for haemoglobin synthesis for oxygen transport and its deficiency leads to anaemia an aged phenotype occurs through enhancement in IL-6, TGFβ signalling. Sodium shows its effect by action of aldosterone on muscle cells and helps in heart function deficiency leads to heart diseases an aged phenotype occurs through increased SIRT1, mTORC1 signalling. Zinc well known for immune defence through inhibition of NFκB signalling deficiency leads to reduced immunity through enhancement of this signalling. A summary of different minerals and their mechanism of action along with their

associated signalling pathway with ageing had described in **Table 1**.

), Iron (Fe), Sodium (Na), Zinc (Zn) along with mecha-

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

), Iodide (I−

Fluoride (F−

#### **Table 1.**

*Summary of mineral elements mechanism of action and association with longevity.*

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

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

**Mechanism of action**

Bone mineralisation

Contraction of smooth muscle cell [44]

Bone calcification through formation of hydroxyl apatite

Protects neuronal cell death by activating PI3K/Akt signalling [51]

Reduces muscle pain and body pain

Prevents dental caries by remineralisation of enamel and improving acid resistance [74]

Prevents thyroid enlargement through T3 &T4 [76]

Haemoglobin formation through erythropoiesis [59]

Regulates heart function through IP3signaling by aldosterone [100–102]

Reduces intracellular ROS by activating SOD, NOX, MT [112]

*Abbreviations: FGF-fibroblast growth factor, SOD-superoxide dismutase, NOX-NADPH oxidase,* 

*Summary of mineral elements mechanism of action and association with longevity.*

*MT-metallothionin, T3-tri iodothyronine, T4-tetra iodothyronine, PI3K-Phosphatidyl inositol 3 kinase, MAPKmitogen activated protein kinase, Wnt-Wingless-related integration site, Nrf 2-nucleoid erythroid receptor factor 2, TSH-thyroid stimulating hormone, TGF-tumour growth factor, SIRT 1-sirutin1, mTORC1-mammalian target of* 

[55–57]

crystals

through hydroxyapatite formation [35]

**Deficiency disease**

Muscle weakness, mental retardation

Rickets, Osteoporosis, Osteopetrosis (marble bone disease)

Neuromuscular weakness, muscle irritation

Muscle fatigue, convulsions

Goitre, Myxoedema

Growth retardation, hypogonadism, decreased immunity

Hypochromic microcytic anaemia

Dental caries KLF 4

Heart disease SIRT1,

**Signalling pathway associated with ageing**

[36, 37]

mTORC1 signalling [47]

Wnt, MAPK pathway [49]

Nrf 2 pathway [53, 54]

Redox signalling [60–62]

pathway [75]

TSH signalling [78]

TGF-β signalling [96]

mTORC1 signalling [103, 104]

NFkB signalling [113, 114]

Osteomalacia FGF signalling

**Mineral Physiological** 

Phosphorous (P)

Potassium (K)

Calcium (Ca)

Magnesium (Mg)

**function**

Formation of high energy phosphates, nucleic acids, nucleotide coenzymes

Chief cation of intracellular fluid, osmotic balance, muscle function

Development of bones, muscle contraction, blood coagulation, nerve transmission, intracellular messenger etc.

Constituent of bones, cofactor for

vitamins, heparin, chondroitin sulphate

of thyroxine, triiodothyronine

in constituent of

extracellular fluid, osmotic balance, acid–base balance, nerve function

dehydrogenase, carbonic anhydrase, lactate dehydrogenase

*rapamycin complex 1, NFkB-natural factor kappa beta.*

kinases

Sulphur (S) Constituent of

Fluorine (F) Formation of bones and teeth

Iodine (I) Constituent

Iron (Fe) Transports oxygen

Sodium (Na) Chief cation of

Zinc (Zn) Cofactor for alcohol

heme

**38**

**Table 1.**

varies from infants to adults, gender excess amounts shows hyper forms, and low amounts leads to hypo effects. Mineral deficiencies mostly show aged phenotype and age related diseases have mineral deficiencies. In their absence cell, survival pathways are mostly non-functional and leads to decreased metabolic function that is characterised by aged phenotype. Minerals classified mostly upon their requirement as 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)). A selected mineral with their function importance in mammals have been described in detail in which Phosphorous (P), Potassium (K), Calcium (Ca), Magnesium (Mg), Sulphur (S), Fluoride (F− ), Iodide (I− ), Iron (Fe), Sodium (Na), Zinc (Zn) along with mechanism of action and its diseased mechanism associated with ageing. Phosphorous is involved in bone mineralisation from osteocyte through hydroxyl apatite formation and deficiency leads to osteomalacia that related to ageing through increased fibroblast growth factor signalling. Potassium is involved in muscle contraction and its deficiency leads to muscle weakness and shows aged phenotype through enhanced mTORC1 signalling. Calcium is involved in bone calcification through hydroxyl apatite crystals its deficiency leads to bone disorders shows aged phenotype through dysregulated Wnt, MAPK pathway. Magnesium is involved in protection of neuron from degeneration through inhibition of GSK3β signalling and hyper activation of PI3K, Akt signalling and shows aged phenotype through dysregulated Nrf 2 pathway. Sulphur is involved in prevention of muscle pains and joint pains by reducing inflammation by scavenging free radicals its deficiency leads to muscle fatigue shows aged phenotype through reduced redox signalling. Fluorine is involved protection of enamel layer by remineralisation, crystallisation of dentine and enhancement in acid resistance its deficiency leads to dental caries which is also an aged phenotype due to disturbed KLF4pathway. Iodine is necessary for thyroid gland for production of thyroid hormones deficiency of it leads to goitre that is characterised by thyroid gland enlargement seen mostly in aged people or people taking iodine deficient diets that occurs through reduced TSH signalling. Iron is necessary for body for haemoglobin synthesis for oxygen transport and its deficiency leads to anaemia an aged phenotype occurs through enhancement in IL-6, TGFβ signalling. Sodium shows its effect by action of aldosterone on muscle cells and helps in heart function deficiency leads to heart diseases an aged phenotype occurs through increased SIRT1, mTORC1 signalling. Zinc well known for immune defence through inhibition of NFκB signalling deficiency leads to reduced immunity through enhancement of this signalling. A summary of different minerals and their mechanism of action along with their associated signalling pathway with ageing had described in **Table 1**.
