Normal and abnormal aging (general perspective for the oncologist)

Normal aging, from maturity to senescence, is accompanied by a large number of physiologic, organ, biochemical, and molecular changes. In the unchallenged state, at homeostasis, age-related decrements in function from these changes are few in part because reserves are used to maintain homeostasis. When challenged, whether by diseases, environment, medications, etc., those age-related changes become apparent. These changes lead to increased vulnerability with aging, called “homeostenosis.” Rather than the reserves disappearing with age, the reserves are invoked in the older person just to maintain homeostasis. Therefore, less are available to respond to disease or medication or other challenge. Broadly this pattern is seen in the cardiovascular system, the hematological system, and the renal system, and elsewhere. When there are essentially no reserves available for challenges, when any challenge overwhelms them, that is frailty. Additionally, aging can modify the impact, presentation, and natural history of any illness. This is because the substrate, the aging person, more than the disease pathophysiology, has been modified. In any given person, the system where the reserves are the least may be the most likely to fail with any challenge. For example, in older patients with dementia, delirium may be the presenting symptom for a urinary tract infection, gastrointestinal bleed, or myocardial infarction; the weakest link fails first. Understanding homeostenosis helps one to understand the apparent vulnerability of the elderly that are in our care.