Introduction: The Gap Between Aging Biology and Everyday Oncology
In earlier parts of this Expert Series, we have explored:
- Epigenetic clocks and ImAge as tools to quantify “how old” tissues and cells are
- Tissue- and genotype-specific profiles of aging
- How lymphoma and cancer therapies can accelerate systemic aging
- Reproductive aging and women’s cancer risk
- The KRAS-driven lung cancer model as an example where aging does not simply accelerate tumorigenesis
- Diet, exercise, environment, and geography as external drivers of the aging × cancer risk landscape
Together, these discussions have highlighted that:
- Aging is a multidimensional process, not a single scalar “speed”
- Cancer is not just a disease that happens on top of aging, but a phenomenon that interacts with aging at multiple levels
In clinical practice, however, decisions are typically based on:
- Chronological age
- Performance status
- Organ function, comorbidities, and patient preferences
Oncologists must answer very concrete questions:
- “How aggressive should we be with treatment for this patient?”
- “Which regimen and dose are realistic, given risks and benefits?”
How can insights from aging biology actually inform such day-to-day decisions? In this article, from the perspective of geriatric oncology, we will discuss:
- How cancers in older adults differ from those in younger patients
- How to incorporate “biological age” into assessment and decision-making
- The roles of geriatric assessment, frailty, and emerging aging biomarkers
- Implications for prevention, screening, treatment choices, and survivorship
Cancer in Older Adults Is Not Just “Cancer in an Older Body”
1) Key Features of Older Cancer Patients: Comorbidities, Polypharmacy, Reduced Reserve
Epidemiologically, the majority of cancer diagnoses occur in older adults. What makes clinical care challenging is not only the cancer itself but also:
- Multiple comorbidities (hypertension, diabetes, cardiac disease, renal impairment, cognitive decline)
- Polypharmacy and the associated risks of drug–drug interactions and adverse effects
- Reduced organ reserve (heart, lungs, kidneys, bone marrow)
- Sarcopenia, frailty, and fall risk
Even when two patients have the same cancer type and stage and receive the same regimen, toxicity profiles and treatment completion rates can differ dramatically between younger and older patients.
2) Chronological vs Biological Age: Same 80 Years, Very Different Aging Trajectories
From an aging-biology standpoint, the core challenge is that:
- Chronological age (calendar age) often diverges from biological age (actual functional and organ age)
Among 80-year-olds, for instance, we may see:
- Individuals who are fully independent, with few comorbidities and preserved muscle mass and cognition
- Others with multiple chronic diseases, marked sarcopenia, mild cognitive impairment, and dependence in daily activities
These patients have very different capacities to tolerate systemic therapy, even though their chronological ages are identical. This is why:
- Relying on age alone to decide that “someone is too old” or “still young enough” for aggressive therapy is scientifically and ethically inadequate
Comprehensive Geriatric Assessment (CGA) and Frailty
1) What Is CGA? A Multidimensional Framework for Older Patients
Geriatric oncology emphasizes the use of:
- CGA (Comprehensive Geriatric Assessment)
CGA systematically evaluates:
- Physical function (ADL, IADL)
- Cognitive function
- Mood and depressive symptoms
- Nutritional status and weight change
- Comorbidities
- Medication use and polypharmacy
- Social support and living situation
It is used to:
- Estimate the risk of treatment-related toxicity and treatment completion
- Identify non-cancer issues that require intervention (nutrition, rehabilitation, social support)
2) Frailty and Sarcopenia: Practical Indicators of Aging and Treatment Tolerance
Frailty indices based on gait speed, grip strength, weight loss, fatigue, and activity level, as well as imaging-based assessments of muscle mass (sarcopenia), have emerged as important predictors of:
- Chemotherapy toxicity
- Postoperative complications
- Overall survival
These measures capture aspects of “functional aging” and body composition that often explain treatment tolerance better than chronological age alone.
Aging Biomarkers in the Clinic: Promise and Limitations
1) Epigenetic Clocks, ImAge, and Circulating Markers
At the research level, a variety of aging biomarkers have been proposed, including:
- DNA methylation–based epigenetic clocks
- ImAge and related image-derived aging metrics at the single-cell level
- Inflammatory markers (e.g., CRP, IL-6) and metabolic markers
These are being evaluated for their ability to:
- Predict disease and mortality risk beyond chronological age
- Forecast treatment toxicity and response in cancer patients
2) Why Are They Not Yet Widely Used in Routine Practice?
Despite their scientific appeal, aging biomarkers are not yet widely implemented in everyday oncology. Reasons include:
- Lack of standardization in measurement methods and cutoffs
- Unclear clinical use cases—how exactly they should change decisions
- Cost, reimbursement, and workflow issues
For now, aging biomarkers remain primarily research tools, while clinical decisions lean more heavily on CGA, frailty, and functional assessments.
Designing Cancer Treatment for Older Adults: Intensity, Goals, and Time Horizon
1) Defining Goals: Cure, Disease Control, or Symptom Relief?
In older patients, treatment planning should explicitly consider:
- Cancer type and stage
- Estimated life expectancy (including non-cancer factors)
- Patient values and priorities for quality of life
Possible goals range from:
- Curative intent
- Slowing disease progression while preserving quality of life
- Focusing primarily on symptom relief and comfort
Insights from aging biology and geriatric assessment can help answer a key question:
- “Given this patient’s reserve and aging trajectory, what level of treatment intensity is realistic and appropriate?”
2) Chemotherapy, Targeted Agents, and Immunotherapy in Older Adults
Specific considerations include:
- Dose adjustments based on renal, hepatic, and marrow function
- Drug–drug interactions in the context of polypharmacy (especially for oral targeted agents)
- Immune-related adverse events with checkpoint inhibitors in aged immune systems
In highly frail or sarcopenic patients, the right answer may not be “reduced-dose standard therapy” but an altogether different strategy—greater reliance on local treatments, symptom-directed care, or best supportive care.
Prevention and Screening: Age- and Aging-Aware Strategies
1) Cancer Screening: When to Start and When to Stop
Appropriate age thresholds for starting and stopping screening depend on:
- The natural history of each cancer
- Sensitivity and specificity of screening tests
- Treatability and expected benefit within a person’s remaining life expectancy
From an aging-informed perspective, there is growing interest in tailoring screening not by chronological age alone but by:
- Estimated life expectancy and overall aging status
For example:
- Biologically “younger” 80-year-olds with high functional status might benefit from continued screening similar to that used in younger cohorts
- Individuals with severe frailty and limited life expectancy may be better served by focusing on symptom management rather than detecting asymptomatic early-stage disease
2) Lifestyle Interventions Across the Life Course
Lifestyle interventions (smoking cessation, weight management, physical activity) are most powerful when started earlier in life, but even in older age they can:
- Improve cardiopulmonary function
- Prevent or mitigate sarcopenia and frailty
- Reduce treatment toxicity and hospitalizations
An aging-aware approach might emphasize different priorities at different stages:
- Midlife: targeting obesity, smoking, and inactivity to slow metabolic and inflammatory aging
- Early older age: resistance and balance training to maintain muscle and reduce falls
- Late older age: avoiding overly restrictive diets and focusing on adequate nutrition, gentle activity, and social engagement
Multidisciplinary Teams and Shared Decision-Making
1) Cancer Care for Older Adults Requires More Than Oncology Alone
Optimal care for older cancer patients often involves:
- Geriatric medicine
- Rehabilitation specialists
- Nutrition support teams
- Psycho-oncology and palliative care
- Social workers and care coordinators
To bring aging biology into the clinic, teams need shared answers to questions such as:
- “Which measures of aging or frailty will we use?”
- “How will those measures concretely influence our treatment plans?”
2) Shared Decision-Making with Patients and Families
In older adults, cancer care decisions are tightly interwoven with:
- Quality of life
- Caregiving capacity and burden
- Financial and social consequences
Aging-informed assessments can provide a clearer picture of:
- “What is realistically achievable, and at what cost in terms of risk and function?”
But they should be used in the context of shared decision-making, where patient values and goals lead, and biology informs—not dictates—the conversation.
Conclusion: Translating Aging Biology into Bedside Language
In this eighth Expert Series article, we have:
- Described how cancers in older adults differ not only because of age but because of comorbidities, polypharmacy, and reduced reserve
- Reviewed practical tools such as CGA, frailty indices, and muscle-mass assessments to capture aging in the clinic
- Considered the potential and limitations of aging biomarkers such as epigenetic clocks and ImAge
- Discussed implications for setting treatment goals, tailoring intensity, and refining prevention and screening strategies
- Emphasized the importance of multidisciplinary teams and shared decision-making
The central challenge is to translate complex aging biology into the everyday language of clinical decisions: “What treatment, for this patient, at this time?” Aging science reminds us that:
- “Patients of the same chronological age may be on very different aging trajectories, and respectful care must take those differences seriously.”
In future parts of this series, we will apply this framework to specific cancer types (e.g., breast, colorectal, hematologic malignancies) and to case-based scenarios that illustrate aging-aware decision-making in practice.
My Thoughts
Reading aging-biology papers, it is easy to be captivated by elegant epigenetic signatures and high-dimensional single-cell maps. At the bedside, though, the questions are starkly concrete: “How many good months or years might this 80-year-old gain from treatment, and at what cost?” Geriatric oncology sits at this interface between abstraction and reality, trying to make cutting-edge biology speak to the decisions that matter most to patients.
To me, the most constructive way to use aging biology in the clinic is not as a gatekeeper, but as a conversation starter. Epigenetic clocks and frailty scales should not be tools for saying, “You are too old for treatment,” but starting points for a dialogue: “This is how your body appears in terms of reserve and risk—knowing that, what matters most to you, and what trade-offs are acceptable?”
There will rarely be a single “right” answer at the intersection of aging and cancer. But if aging biology can help patients, families, and clinicians reach decisions that feel more informed and more aligned with what each person values, then it will have served a meaningful purpose. That is the spirit in which this series approaches the topic.
This article has been edited by the Morningglorysciences team.
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