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Review
. 2022 Jan 29;11(3):468.
doi: 10.3390/cells11030468.

How to Slow down the Ticking Clock: Age-Associated Epigenetic Alterations and Related Interventions to Extend Life Span

Anne-Marie Galow  1 , Shahaf Peleg  2   3
Affiliations
Review

How to Slow down the Ticking Clock: Age-Associated Epigenetic Alterations and Related Interventions to Extend Life Span

Anne-Marie Galow et al. Cells. .

Abstract

Epigenetic alterations pose one major hallmark of organismal aging. Here, we provide an overview on recent findings describing the epigenetic changes that arise during aging and in related maladies such as neurodegeneration and cancer. Specifically, we focus on alterations of histone modifications and DNA methylation and illustrate the link with metabolic pathways. Age-related epigenetic, transcriptional and metabolic deregulations are highly interconnected, which renders dissociating cause and effect complicated. However, growing amounts of evidence support the notion that aging is not only accompanied by epigenetic alterations, but also at least in part induced by those. DNA methylation clocks emerged as a tool to objectively determine biological aging and turned out as a valuable source in search of factors positively and negatively impacting human life span. Moreover, specific epigenetic signatures can be used as biomarkers for age-associated disorders or even as targets for therapeutic approaches, as will be covered in this review. Finally, we summarize recent potential intervention strategies that target epigenetic mechanisms to extend healthy life span and provide an outlook on future developments in the field of longevity research.

Keywords: DNA methylation; DNAm age; accelerated epigenetic aging; age-associated disorders; biomarker; deep learning; health span; histone modification; longevity; metabolism; methylation clock; microbiome; single-cell sequencing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Relevant milestones in research on epigenetic aging and longevity interventions. While research in the 1950s built the foundation for epigenetic studies and in-depth analyses of longevity factors at the beginning of the new century, recent research focuses more and more on methods to directly exploit epigenetic mechanisms to prevent or even reset aging.
Figure 2
Figure 2
Age-related alterations and potential underlying mechanisms. Aging induces a number of metabolic and functional changes that result in a modified activity of epigenetic enzymes, eventually causing the altered epigenetic landscape of aged organisms exemplified here. However, it is not possible to deduce a general road map for epigenetic aging, as individual alterations can be specific for species, genders, tissues and cell types. Moreover, the complex interplay of the diverse regulation mechanisms is still poorly understood and likely changes at various stages throughout life.
Figure 3
Figure 3
Factors that either negatively or positively affect epigenetic aging. Epigenetic aging as determined with DNAm clocks is accelerated in consequence of several diseases and further negatively affected by some concomitant conditions of certain lifestyles. On the other hand, there are some hereditary and environmental factors that are associated with slowed epigenetic aging.
Figure 4
Figure 4
Pharmacological and environmental longevity interventions impacting epigenetic mechanisms. A number of pharmacological substances mediate their beneficial effects on life span via epigenetic enzymes or upstream regulators that influence levels of crucial metabolites. Caloric restriction was demonstrated to positively affect life span acting via similar mechanisms, while some amino acids and vitamins support the generation of metabolites for methylation and acetylation.
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