**2.4 Magnesium (Mg)**

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

an antioxidant responsive protein plays a role in protection of cells from oxidative stress and essential for optimal activity inside the cell [52]. The role of magnesium in neuro degeneration shown in **Figure 2d.** Dysregulated Nrf-2 activity in neurodegenerative diseases linked to ageing [53, 54]. The signalling pathway connecting magnesium deficiency and ageing shown in **Figure 3**.

2.5 Sulphur (S): Egg white, chicken, fish, beef are major sources of sulphur. Daily intake is 14 mg for healthy adult and distributed in nails, hair, and skin. Sulphur plays a role as antioxidant, anti-inflammation, metal transport, free radical scavenging, protein stabilisation, xenobiotic detoxification, metabolism of lipids. Sulphur resides inside the body in organic form as methionine, cysteine, and cysteine functions as part of vitamins such as thiamine, biotin, and coenzyme A and excreted through oxidised form as taurine and cholic acid. Deficiency diseases are almost unknown. Although reports revealed that, sulphur containing amino acids in the form of methionine and cysteine forms creatinine, carnitine and coenzyme. Sulphur in the form of methylsulfonylmethane (MSM) acts to prevent muscle pains and joint pains through reduction of pro-inflammatory cytokines (NFkB, IL-1, IL-6, IL-8, TNF-α) [55–57] and decreased infiltration of immune cells by reducing inflamed synovial membrane [58, 59]. The role of sulphur in muscle pains and joint pains shown in **Figure 2e**. An essential for muscle functioning and deficiency leads to muscle impairment and aged phenotype. Aged muscle has altered Redox signalling [60–62] and exercised individuals in their lifetime had preserved enough muscle fitness comparable to younger ones [63] whereas NAD+ treatment [28] reverse these effects. Strenuous exercise result in muscle damage [64] and dysregulated redox response within the muscle increase in transient ROS/RNS. This clearly explains redox mechanisms operate with ageing and contraction of skeletal muscle can activate a number of transcription factors thereby affecting gene expression of specific cellular pathways. The signalling pathway connecting sulphur deficiency and ageing shown in **Figure 3**.
