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Gene & Protein in Disease Buccal mucosa and aging

can trigger premature aging syndromes, such as Werner been studied for their effects on aging. For instance, the
syndrome, Cockayne syndrome, Bloom’s syndrome, and absence of GSTM1 and GSTT1 83,102 has been associated
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ataxia telangiectasia, suggesting possible roles of replicative with aging, and polymorphisms in the GSTP1 gene have
senescence genes in the aging process. CDK6, CCND1, and demonstrated both progressive 24,111,112 and non-progressive
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p16 are examples of such genes that contribute to aging. effects 24,113 on the aging process.
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The CDK6 and CCND1 genes play crucial roles in regulating Another significant activator of cellular senescence
the cell cycle through the retinoblastoma pathway and is telomere dysfunction, which operates through the G1
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in growth arrest alongside the p16 and Rb genes. During DNA damage checkpoint and the upregulation of p21/p16.
senescence, the Rb and p53 genes are activated but gradually Telomeres are complex DNA-protein structures at the ends
lose their ability to regulate cell proliferation. 91
of eukaryotic chromosomes, and their shortening serves as
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Many genes involved in aging are primarily located on a marker of DNA damage in cells. By capping chromosome
chromosomes 1, 4, 6, 7, and 20. Telomerase suppressor ends, telomeres prevent nucleolytic degradation, end-
genes are found on chromosomes 3 and 4, whereas the to-end fusion, irregular recombination, and other lethal
WRN gene, which is associated with Werner syndrome cellular events. Telomere length is inversely correlated
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and premature aging, is localized on chromosome 8. with age and shortens in all replicating somatic cells,
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88
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Several genes also serve as biomarkers for susceptibility including NK cells, which are crucial for recognizing
to environmental damage. This group includes genes and eliminating senescent cells. As telomere shortening
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from the CYP and GST families, which are crucial for the progresses with age, it gradually impairs NK cell function.
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metabolism and detoxification of environmental hazards The functional activities of NK cells, such as cytokine
and xenobiotics. 103,104 CYP enzymes contribute to phase I production in CD56 bright cells and cytotoxic activity in
xenobiotic metabolism by oxidizing compounds, leading CD56 cells, shift with aging – CD56 bright cells decrease
dim
to the formation of active substances and highly reactive whereas CD56 cells increase. {Weber, 2024 #118} This
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dim
mutagenic metabolites. Key members of this group shift results in impaired immunity and a heightened risk of
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104
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include CYP1A1, CYP1A2, and CYP2E1. While CYP1A1 age-related diseases. These changes are associated with
and CYP1A2 have been documented to potentially declines in biomarkers such as IL-2, IL-15, and CD56 bright ,
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offer protective effects against DNA damage and aging, alongside increases in others such as IL-6, IFN-γ, and
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some reports suggest paradoxical effects, particularly CD38, all of which contribute to accelerated aging and
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for CYP1A1. For instance, polymorphisms in CYP2E1 age-related health issues. Consequently, these changes
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have been shown to impact aging 24,107 by inducing DNA lead to a weakened immune response and increased
damage. 107-109 The GST family, also involved in xenobiotic inflammation associated with aging, making NK cells a
metabolism, detoxifies xenobiotics. Notable members significant target for interventions aimed at mitigating age-
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include the GSTT1, GSTM1, and GSTP1 genes, which have related immune decline. In addition, the function of NK

Figure 4. Consequences of DNA damage following chemical exposure

Volume 3 Issue 4 (2024) 6 doi: 10.36922/gpd.4418