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The Frontier of Life Science

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The 12 Hallmarks of Aging and Metabolism Research: Reactive Oxygen Species, Mitochondria, and Cellular Senescence

Metabolism and Aging Research

Metabolism refers to all the chemical reactions by which living organisms obtain energy from nutrients, store it, and synthesize and break down the substances that make up the body. Aging is the process by which physiological function gradually declines over time, and it is known to be the greatest risk factor for many chronic diseases.

In the biology of aging, the molecular and cellular features of aging observed in common across many species have been organized as the “hallmarks of aging.” This framework, presented with 9 hallmarks in 2013, was expanded to 12 in 2023, and nutrient-sensing pathways, mitochondrial function, cellular senescence, and chronic inflammation are closely connected to metabolism research.

Genomic instabilityTelomere attritionEpigenetic alterationsLoss of proteostasisDisabled autophagyDeregulated nutrient sensingMitochondrial dysfunctionCellular senescenceStem cell exhaustionAltered intercellular communicationChronic inflammationDysbiosis

Main research topics

  • 01
    Nutrient-sensing pathways

    Metabolic regulatory signals such as insulin/IGF-1, mTOR, AMPK, and sirtuins

  • 02
    Mitochondria and energy metabolism

    Oxidative phosphorylation, reactive oxygen species, and mitochondrial quality control

  • 03
    Cellular senescence

    Accumulation of senescent cells, their secretory phenotype, and strategies for clearing them

  • 04
    Autophagy and proteostasis

    Mechanisms for breaking down and recycling damaged components inside cells

  • 05
    Chronic low-grade inflammation

    Regulation of the inflammatory state that increases with aging (inflammaging)

  • 06
    Muscle and adipose tissue metabolism

    The relationship between sarcopenia, adipose tissue function, and whole-body metabolism

Overview of methods

01Model organisms

Lifespan and healthspan are examined in yeast, nematodes, fruit flies, mice, and other organisms.

02Metabolic phenotypes

Markers of glucose and lipid metabolism and energy expenditure are measured.

03Markers of cellular senescence

Senescence-associated markers and cell cycle arrest are evaluated.

04Aging biomarkers

Indicators of biological age, such as epigenetic clocks, are studied.

05Multi-omics

Pathways are linked through integrated genome and metabolome analysis.

References
  1. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell 2013;153(6):1194–1217.
  2. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: An expanding universe. Cell 2023;186(2):243–278.