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Review
. 2024 May 6;25(9):5044.
doi: 10.3390/ijms25095044.

Emerging Roles of Vitamin B12 in Aging and Inflammation

Sergey Yu Simonenko  1 , Daria A Bogdanova  2 , Nikita A Kuldyushev  1
Affiliations
Review

Emerging Roles of Vitamin B12 in Aging and Inflammation

Sergey Yu Simonenko et al. Int J Mol Sci. .

Abstract

Vitamin B12 (cobalamin) is an essential nutrient for humans and animals. Metabolically active forms of B12-methylcobalamin and 5-deoxyadenosylcobalamin are cofactors for the enzymes methionine synthase and mitochondrial methylmalonyl-CoA mutase. Malfunction of these enzymes due to a scarcity of vitamin B12 leads to disturbance of one-carbon metabolism and impaired mitochondrial function. A significant fraction of the population (up to 20%) is deficient in vitamin B12, with a higher rate of deficiency among elderly people. B12 deficiency is associated with numerous hallmarks of aging at the cellular and organismal levels. Cellular senescence is characterized by high levels of DNA damage by metabolic abnormalities, increased mitochondrial dysfunction, and disturbance of epigenetic regulation. B12 deficiency could be responsible for or play a crucial part in these disorders. In this review, we focus on a comprehensive analysis of molecular mechanisms through which vitamin B12 influences aging. We review new data about how deficiency in vitamin B12 may accelerate cellular aging. Despite indications that vitamin B12 has an important role in health and healthy aging, knowledge of the influence of vitamin B12 on aging is still limited and requires further research.

Keywords: aging; cobalamin; inflammation; protein modifications; senescence; vitamin B12.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Vitamin B12 transport and cobalamin structural forms.
Figure 2
Figure 2
MMUT function in mitochondria. Propionate formed from the catabolism of branched amino acids and odd-chain fatty acids is converted to D-methylmalonyl-CoA. Methylmanolyl-CoA epimerase isomerizes D-methylmalonyl-CoA to the L-form. L-methylmalonyl-CoA is the substrate for MMUT, converting it to succinyl-CoA, which enters the TCA cycle. Abbreviations: MMA—methylmalonic acid, TCA cycle—the tricarboxylic acid cycle.
Figure 3
Figure 3
The MS catalytic cycle and its connection to cellular metabolism. Red arrows indicate the pathway of a methyl radical. Abbreviations: MS—methionine synthase, THF—[5,6,7,8]-tetrahydrofolate, DHF—[7,8]-dihydrofolate, Hcy—L-homocysteine, SAH—S-adenosyl-L-homocysteine, SAM—S-adenosyl-L-methionine, GSH—reduced glutathione, MetCbl—MeCbl, Cbl—cobalamin, CH3˙—methyl radical.
Figure 4
Figure 4
Consequences of vitamin B12 deficiency at cellular, tissue, and organismal levels. Arrows indicate direction of change: ↑—increase, ↓—decrease.
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