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Aging changes
which genes are active.

Tissue-maintenance genes lose activity. Normally silent viral DNA escapes repression. Explore two ways that gene regulation changes with age.

Epigenetic regulation

Illustrated transition: old → young
lifga.Illustrative model
Constitutive heterochromatin
Old state
Viral genes: HERV-K gag / pol / env
Lower methylation · looser packingHERV-K genes ACTIVE
Current state
Young state
CpG-island promoters
Old state
Maintenance gene: ELOVL2
Higher methylation · tighter packingELOVL2 expression LOWER
Current state
Young state
Methylated CpGUnmethylated
Oldest
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Simplified model · gene switching shown for selected promoters
Loading portrait sequence.
Read both strands together: toward the young state, viral DNA becomes more tightly repressed while maintenance-gene promoters become more accessible. The animation illustrates these two regulatory patterns.

READING THE MODEL

Keep harmful sequences silent.
Keep maintenance genes active.

DNA wraps around histone proteins to form chromatin. DNA methylation helps determine which regions are repressed and which genes remain accessible. Aging involves both a loss of repression at repetitive DNA and a gain of repression at selected gene promoters.

Upper strand · viral repression

Young: methylation and compact chromatin keep viral genes silent.

Old: methylation and chromatin repression erode; viral genes become active.

Lower strand · gene access

Young: less promoter methylation and greater maintenance-gene activity.

Old: more promoter methylation and reduced gene activity.

Transcription state: In actively expressed genes, CpG-island promoters are typically unmethylated, supporting access by transcription factors and the pre-initiation complex that drives gene expression.

Gene silencing: DNA methyltransferases add methyl groups to cytosines at promoter CpG sites. Promoter hypermethylation promotes chromatin compaction, restricts transcription-factor access and stabilizes gene silencing.

WHAT THESE CHANGES MEAN

Specific genes.
Consequences for aging.

HERV-K · gag / pol / env Human mesenchymal progenitor cells

Ancient viral genes reactivate.

HERV-K is retroviral DNA embedded in the human genome. Its reactivation in senescent cells reinforces senescence and spreads aging signals to neighboring cells.

YOUNG

DNA methylation and repressive chromatin keep these viral genes silent.

OLD / SENESCENT

Methylation and chromatin repression decline; gag, pol and env expression rises.

SFRP1 Human colon

A brake on growth loses activity.

SFRP1 is a tumor-suppressor gene that restrains Wnt signaling, a pathway controlling cell proliferation. Age-associated promoter methylation accompanies a decline in its expression.

YOUNGER

Less promoter methylation. Higher SFRP1 expression.

OLDER

More promoter methylation. Lower SFRP1 expression.

ELOVL2 Mouse retina

A gene supporting vision declines.

ELOVL2 makes long-chain fatty acids needed for retinal function. Its expression falls as its promoter gains methylation with age. Reducing that methylation increased expression and improved visual function in mice.

YOUNG

Lower promoter methylation. Higher ELOVL2 expression.

OLD

Higher promoter methylation. Lower ELOVL2 expression and declining retinal function.

COL1A1 Human periodontal ligament

The collagen-building program weakens.

COL1A1 encodes a major component of type I collagen, which gives connective tissue its tensile strength. In the ligament supporting the teeth, promoter methylation increases with age while COL1A1 expression falls.

YOUNGER

Less promoter methylation. Higher expression of the collagen gene.

OLDER

More promoter methylation. Lower expression of the collagen gene.