Aging is a natural process that affects everyone. In recent years, however, the way researchers understand aging has changed substantially. Rather than viewing it as something that must simply be accepted, scientists increasingly approach aging as a process whose components may offer potential points of intervention once they are understood.
Within this shift, researchers around the world frequently refer to a shared framework known as the Hallmarks of Aging. At NOMON & Co., we refer to this framework as AGING HALLMARKS, and that term is used throughout this article. Here, we explain what the AGING HALLMARKS are and why they have become important in aging research.
What You Will Learn
- The basic concept of the AGING HALLMARKS, or Hallmarks of Aging
- Who proposed the framework, when, and why
- Why the original nine hallmarks published in 2013 were expanded to 12 in 2023
- The three criteria a biological process must meet to be recognized as a hallmark
- What everyday habits may mean when viewed through the AGING HALLMARKS framework
What Are the AGING HALLMARKS?
The AGING HALLMARKS—formally known as the Hallmarks of Aging—are a framework that organizes and classifies the complex phenomenon of aging according to shared biological mechanisms.
Aging has many dimensions. By systematically organizing changes at the molecular, cellular, and system levels, researchers created a common language for the field.
The current AGING HALLMARKS framework comprises 12 hallmarks across three categories.
- Primary hallmarks: The fundamental causes of aging—the initial sources of damage
- Antagonistic hallmarks: The body’s responses to the primary hallmarks—defense mechanisms that initially act against damage
- Integrative hallmarks: The consequences that emerge at the tissue and organism levels—the systemic outcomes of the preceding changes
The 12 hallmarks are not independent phenomena. They influence one another. Genomic instability, epigenetic alterations, and mitochondrial dysfunction, for example, do not occur in isolation. Research indicates that these processes interact and collectively contribute to the progression of aging.
- Genome
- The complete set of genetic information carried by an organism.
- Epigenetic alterations
- Changes in patterns that regulate whether genes are switched on or off without changing the underlying DNA sequence.
- Mitochondria
- Cellular structures that generate much of the energy used by cells.
Who Proposed the Framework?
The AGING HALLMARKS framework was introduced in a 2013 paper published in Cell by an international research team led by Professor Carlos López-Otín of the University of Oviedo in Spain1.
The coauthors—Blasco, Partridge, Serrano, and Kroemer—were leaders in telomere research, the biology of aging, cellular senescence, immunology, and metabolism. The paper brought together knowledge across these fields.
Since its publication, the article has become one of the most highly cited papers in aging research and has provided a shared foundation for researchers worldwide.
- Telomeres
- Protective DNA structures at the ends of chromosomes. They shorten each time a cell divides, and when they become critically short, the cell can no longer divide normally.
From Nine Hallmarks in 2013 to 12 in 2023
The original 2013 framework described aging in terms of nine hallmarks.
Over the following decade, aging research advanced rapidly. Findings that had initially come largely from non-mammalian model organisms such as yeast and nematodes were increasingly examined in mice and primates. In 2023, López-Otín and colleagues published a major update in Cell, redefining the framework around 12 hallmarks2.
Three hallmarks were added:
- Disabled macroautophagy: Declining capacity for cellular repair and recycling
- Chronic inflammation
- Dysbiosis: Alteration of the gut microbiome
These processes had already been under investigation, but the evidence accumulated over the decade was considered sufficient for them to be recognized as independent hallmarks.
Three Criteria for Recognition as a Hallmark
The AGING HALLMARKS are not simply a list of changes observed with aging. López-Otín and colleagues defined hallmarks as processes that satisfy three premises:
- The process appears during aging: The change is observed during normal aging.
- Experimentally intensifying the process accelerates aging: Increasing the change under experimental conditions causes aging-related deterioration to occur more rapidly.
- Intervening in the process may delay, halt, or reverse aspects of aging: Improving the change has the potential to extend healthspan. This criterion has been demonstrated mainly in model organisms such as mice, while research in humans remains ongoing.
The third criterion is particularly important: the biological processes included in the AGING HALLMARKS may provide potential points of intervention.
One prominent example of the growing effort to intervene in aging is XPRIZE Healthspan, launched in 2023. This seven-year international competition, organized by the XPRIZE Foundation, offers a total prize purse of US$101 million—approximately ¥15 billion. It challenges teams worldwide to develop approaches that restore muscle, cognitive, and immune function in people aged 50–80 by the equivalent of at least 10 years, with a target of 20 years. More than 600 teams from 58 countries are participating. The idea that aspects of aging may be modifiable has therefore moved beyond academic discussion into a large-scale global challenge.
Everyday Habits Through the AGING HALLMARKS Lens
Intervention in aging does not refer only to specialized treatments or advanced technologies. Research suggests that everyday habits—including physical activity, diet, and sleep—may influence processes represented in the hallmarks.
- Moderate exercise: Numerous studies associate physical activity with maintenance of ⑦ mitochondrial function, activation of ⑨ stem-cell function, and modulation of ⑪ chronic inflammation.
- A balanced diet: Dietary patterns are related to regulation of ⑥ nutrient-sensing pathways and maintenance of ⑫ gut-microbiome diversity.
- High-quality sleep: Sleep has been associated with ⑤ autophagy, a cellular repair and recycling process.
- Stress management: Stress regulation may influence ⑪ chronic inflammation and ② telomere attrition.
These points reflect current research findings. Effects may differ among individuals and depend on the conditions studied.
Aging is unavoidable, but everyday choices may influence its pace and the way it affects health. The AGING HALLMARKS can be viewed as a map for considering where evidence-based action may be possible. A first step may be as simple as changing one daily habit.
At NOMON & Co., we are also developing solutions organized around the 12 biological processes in the AGING HALLMARKS framework.
- Learn more about the 12 hallmarks on the NOMON & Co. research and development page.
- 👉 Research and Development for Modulating Aging Based on the AGING HALLMARKS | NOMON & Co.
