Introduction: Adding Lifestyle and Environment to the Genetics–Aging Framework
In previous parts of this Expert Series, we focused primarily on “internal” factors:
- Epigenetic clocks and ImAge as tools to visualize aging
- Tissue- and genotype-specific aging profiles
- Lymphoma and cancer therapy as drivers of systemic aging
- Reproductive aging and women’s cancer risk
- KRAS-driven lung cancer as an example where aging does not simply accelerate tumorigenesis
In real life, however, an individual’s trajectory of aging and cancer risk is shaped not only by intrinsic biology but by:
- Diet, physical activity, sleep, stress, smoking, alcohol
- Environmental exposures (pollution, UV, occupational hazards)
- Geography, socioeconomic conditions, and health-care systems
In this article, we will look at aging × cancer from the perspective of these “external drivers”, focusing on:
- Diet and nutrition
- Exercise and muscle mass
- Environmental exposures such as tobacco, air pollution, and UV
- Geographic and social determinants
The goal is not to provide an exhaustive review of each topic, but to highlight how lifestyle and environment simultaneously influence aging processes and cancer risk—and how they interact with genetics and biology across the life course.
A Life-Course Perspective: From Early Life to Old Age
Early-Life Influences: Development, Epigenome, and Embedded Risk
While aging is often framed as a phenomenon of later life, the foundations of both aging and cancer risk are laid much earlier, including:
- Prenatal and perinatal periods
- Childhood and adolescence
Examples include:
- Associations between birth weight and childhood nutrition with adult obesity, diabetes, and cardiovascular disease
- Secondhand smoke, air pollution, or radiation exposure in early life influencing baseline cancer risk
Epigenetic studies support the idea that early environmental exposures can leave long-lasting marks on DNA methylation and chromatin states, “embedding” risk that may manifest decades later as accelerated aging or disease susceptibility.
Midlife and Older Age: Metabolic and Inflammatory Aging
From midlife onward, we see the emergence of:
- Insulin resistance, dyslipidemia, visceral adiposity
- Chronic low-grade inflammation (“inflammaging”)
- Sarcopenia and declining physical activity
These phenomena are tightly linked to diabetes and cardiovascular disease, but also to increased risk of cancers such as colorectal, liver, pancreatic, endometrial, and postmenopausal breast cancer. In this sense, lifestyle-mediated acceleration of metabolic and inflammatory aging can shift the timing and likelihood of cancer development.
Diet and Aging × Cancer: Calories, Quality, and Timing
Caloric Restriction, Health Span, and Cancer: From Models to Humans
In many model organisms, moderate caloric restriction extends lifespan and reduces cancer incidence. Mechanistically, this is associated with:
- Reduced insulin/IGF-1 signaling
- Downregulation of mTOR activity
- Enhanced autophagy and stress-response pathways
These changes overlap with several “hallmarks of aging.” In humans, long-term, strict caloric restriction is neither practical nor desirable for most people, but:
- Maintaining a healthy body weight
- Avoiding chronic energy excess
- Patterns such as Mediterranean-style diets
have been associated with lower risks of multiple chronic diseases, including some cancers.
Obesity, Insulin Resistance, and Hormone-Related Cancers
Obesity is linked to increased risk of many cancers, including colorectal, liver, pancreatic, endometrial, and postmenopausal breast cancer. Contributing mechanisms include:
- Hyperinsulinemia and elevated IGF-1 signaling
- Increased estrogen production in adipose tissue
- Chronic elevation of inflammatory cytokines such as TNF-α and IL-6
These mechanisms are also central to accelerated aging. Obesity effectively raises “metabolic age” relative to chronological age, influencing not only cancer incidence but tolerance of cancer therapies and overall prognosis.
Diet Quality: Processed Meat, Alcohol, Salt, and Micronutrients
Beyond calories, diet quality also matters for aging and cancer:
- High intake of processed meats is associated with colorectal cancer risk
- High salt intake is linked to gastric cancer and hypertension
- Alcohol consumption increases risk of cancers of the upper aerodigestive tract, liver, and breast
- Higher intake of vegetables, fruits, and dietary fiber is associated with lower risk across several cancer types
Mechanistically, these patterns may influence DNA damage, oxidative stress, local inflammation, and the composition and function of the gut microbiome, thereby affecting both aging trajectories and cancer risk.
Exercise, Muscle Mass, and Aging × Cancer: Sarcopenia and “Active Aging”
Physical Activity and Cancer Incidence
Regular physical activity is associated with reduced risk of several cancers, particularly colorectal, breast, and endometrial cancer. Proposed mechanisms include:
- Improved weight control and reduction of visceral fat
- Improved insulin sensitivity
- Modulation of inflammation and immune function
Exercise may not reverse aging per se, but it can substantially alter how aging manifests at the metabolic, inflammatory, and functional levels.
Sarcopenia and Cancer Outcomes
In older cancer patients, sarcopenia—loss of muscle mass and strength—is increasingly recognized as a negative prognostic factor. Skeletal muscle acts as an endocrine organ that shapes:
- Metabolism and glucose handling
- Inflammatory signaling
- Immune competence
Low muscle mass is associated with:
- Higher toxicity from chemotherapy
- Increased risk of infections and complications
This illustrates that even at the same chronological age, differences in muscle health can reflect and influence biological aging and treatment tolerance.
Environmental Exposures: Tobacco, Air Pollution, UV, and Occupational Hazards
Smoking: A Prototypical Accelerator of Aging and Cancer
Smoking is a classic risk factor for multiple cancers and also for cardiovascular disease, COPD, and other age-related conditions. At the molecular level, smoking causes:
- Extensive DNA damage and mutations
- Chronic oxidative stress and inflammation
- Endothelial dysfunction and vascular injury
From an aging perspective, smoking is a prime example of an exposure that pushes biological age ahead of chronological age, simultaneously increasing cancer risk and accelerating multiple aging-related pathologies.
Air Pollution, Occupational Exposures, and UV Radiation
Air pollution—particularly fine particulate matter (PM2.5)—is associated with elevated risks of lung cancer and cardiovascular disease and is increasingly viewed as an environmental accelerator of aging. Similarly:
- Certain occupational exposures (e.g., benzene, asbestos) are well-established carcinogens
- UV radiation drives both skin aging and skin cancer
These exposures are unevenly distributed across regions and populations, linked to urbanization, industrialization, climate, and workplace regulations. Thus, “where and how people live and work” contributes to geographic patterns of aging and cancer.
Geography and Social Determinants: Longevity Hotspots and Cancer Profiles
Common Features of Longevity Regions
Studies of longevity hotspots (so-called “Blue Zones”) and long-lived regions within countries, such as parts of Japan, highlight common patterns:
- Moderate caloric intake with traditional diets rich in fish, legumes, and vegetables
- Physical activity embedded in daily life rather than isolated exercise sessions
- Lower rates of smoking and heavy drinking
- Strong social networks and community engagement
These factors likely contribute to slower aging trajectories and lower incidence of certain cancers, although cause–effect relationships are complex and intertwined with genetics and health-care systems.
Infections, Screening, and Health-Care Access
Geography also shapes:
- Prevalence of infections such as Helicobacter pylori, HBV/HCV, and HPV
- Availability and uptake of cancer screening (e.g., gastric, colorectal, cervical)
- Access to timely diagnosis and treatment
For example:
- Regions with high hepatitis virus prevalence tend to have more liver cancer in younger and middle-aged adults
- Regions with widespread gastric cancer screening may see both more early detection and, over time, decreased incidence due to H. pylori eradication
These patterns underscore that understanding aging × cancer requires not only biological insight but also attention to public health, infection control, and health-system infrastructure.
Gene × Environment × Aging: Toward Individualized Risk Profiles
Polygenic Risk Scores and Lifestyle
Polygenic risk scores are now being developed for several cancers (e.g., breast, prostate, colorectal), and their interaction with lifestyle factors is an active area of research. When combined with aging markers, this could reveal that:
- The impact of a given lifestyle factor (e.g., obesity, smoking) may differ significantly between individuals with high vs low genetic risk and different trajectories of biological aging
Using Aging Biomarkers to Tailor Prevention and Screening
Looking ahead, one can imagine integrating:
- Biological age metrics (epigenetic clocks, inflammatory markers, functional measures)
- Genetic background
- Lifestyle, environment, and geographic context
to personalize:
- When to start and how often to perform specific cancer screenings
- Which lifestyle interventions to prioritize for a given individual
At present, such approaches remain largely in the research domain; robust validation and careful consideration of ethics and equity will be essential before wide clinical implementation.
Conclusion: How Should We Think About External Drivers of Aging × Cancer?
In this seventh Expert Series article, we have surveyed:
- Accumulation of lifestyle and environmental exposures across the life course
- Diet, obesity, and metabolic/inflammatory aging as joint drivers of cancer
- Exercise, sarcopenia, and their impact on cancer incidence and outcomes
- Environmental hazards such as smoking, air pollution, and UV
- Geographic and social determinants, including infections, screening, and health-care access
The key message is that these external factors do not merely nudge cancer risk up or down; they actively shape how aging unfolds. Genetics, aging, and environment interact to produce highly individual risk profiles.
In future parts of this series, we will build on this perspective to discuss more practical questions:
- How can insights from aging biology be translated into clinical, public-health, and policy strategies?
- What might age-aware, biology-informed approaches to cancer prevention, screening, and treatment look like?
My Thoughts
Messages about “healthy lifestyle” can easily sound generic and moralizing, and as a result, they often fail to resonate. Viewed through the lens of aging biology, however, diet, exercise, and environmental exposures look less like vague recommendations and more like long-term inputs into the trajectory of biological aging itself. Over decades, they help decide not only whether cancer will occur, but which “version” of old age a person will experience.
At the same time, it is essential to avoid slipping into a narrative of pure individual responsibility. Many external drivers—geography, socioeconomic status, occupation, infection burden—are not fully under personal control. Patterns of smoking, diet, and activity are profoundly influenced by culture, industry, pricing, and policy. Understanding external drivers of aging and cancer should therefore inform not only personal choices but also collective decisions about environments, regulations, and health systems.
Ideally, we would treat the risk map of aging × cancer not as a tool for blame or fear, but as a map for designing better futures—for individuals and for societies. That is the spirit in which this series approaches the topic: using biology to expand the range of meaningful choices, rather than to dictate a single “correct” way to live.
This article has been edited by the Morningglorysciences team.
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