A Worse Functional Decline with Age is Observed in Cancer Survivors

It has been established that the standard approaches to cancer, chemotherapy and radiotherapy, produce a sizable additional burden of senescent cells in patients. Indeed, forcing cancerous cells into senescence is a desirable goal in cancer treatment, even at the cost of damaging treatments that make many normal cells senescent as well. A lasting, greater burden of senescent cells accelerates the progression of aging in cancer survivors. Thus there is considerable interest in the research community in applying senolytic treatments to destroy senescent cells following cancer therapy, and thus avoid the cost to long-term health, but this strategy is by no means close to adoption in the medical community at the present time.

Immunotherapy is now the standard of care for many forms of cancer in many parts of the world, certainly an improvement over chemotherapy in the short term, but it remains unclear as to what the various forms of immunotherapy will do to patients over the long term. There is certainly the risk of lasting and evident dysregulation of the immune system for a fraction of patients, such as the onset of autoimmunity triggered by treatment. The immune system is important to health, and its age-related decline influences much of the trajectory of late life mortality. Is it the case that most immunotherapy patients are worse off than their peers in later pace of aging as a result of treatment? That remains to be seen.

Functional decline among older cancer survivors in the Baltimore longitudinal study of aging

Evidence has begun to emerge indicating that cancer survivors experience accelerated aging. This study examines this phenomenon by evaluating trajectories of functional decline in older adults with a history of a cancer diagnosis relative to those without a history of cancer.

Community dwelling healthy volunteers in the Baltimore Longitudinal Study of Aging were evaluated. Between 2006 and 2019, 1,728 men and women (aged 22-100) underwent clinical evaluation of functional status; 359 reported having a history of cancer. Longitudinal associations between self-reported cancer history and measures of functional decline were examined using generalized estimating equations. Additionally, time-to-event and Cox proportional hazards models were used to examine trajectories of decline. Where appropriate, age-stratified associations were examined, and models were adjusted for sex, body mass index, race, smoking status, education, and number of comorbid conditions.

Among all participants, a history of cancer was associated with 1.42 greater odds of weak grip strength. Among older participants (older than 65 years of age), those with a history of cancer had 1.61 greater odds of slow gait speed and a 0.11 unit lower physical performance score than those with no cancer history. Time-to-event analysis showed that older individuals with a history of cancer experienced steeper decline in grip strength and gait speed than older adults with no history of cancer. In conclusion, cancer survivors, especially older individuals, demonstrate greater odds of and accelerated functional decline, suggesting that cancer and/or its treatment may alter aging trajectories.

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