An organismal view of cellular aging

Abstract

Summary This paper reviews the general biological phenomenon of aging as it applies to cells. Philosophical concepts of aging arising from radiation and evolutionary biology are used as a historical context for our understanding of how cells age. The development of multicellularity, and with it, an extracellular matrix is discussed in order to reveal that the biological consequences of aging extend beyond the borders of a cell. The argument is made that an integration of knowledge across levels of biological organization and a unification of theories on aging is needed in order to progress toward a greater understanding of organismal and cellular aging. It is further suggested that complexity theory and a systems level approach provides the means by which that integration can be achieved. The consequences of aging have been observed at virtually every level of biological organization, from molecules to populations. Although explanations of aging are dominated by a few theories (e.g., Kirkwood's (1977) disposable soma theory [1] and Harman's (1956) free radical hypothesis [2] ), countless others have been proffered as well (see Rattan (2006) [3] and Weinert and Timiras (2003) [4] for reviews). This proliferation reflects not only the intricacies of aging but also the need for a theory that integrates information across multiple interacting levels of biological organization. Contrary to reductionist expectation, the number of theories increases rather than decreases at progressively lower levels of biological organization. Nowhere is this more evident than at the cellular level. Thus, it is fitting to devote a special issue to the challenges inherent in understanding the dynamics of cellular aging. There are, however, several obstacles that complicate a discussion of cellular aging. Foremost among them is the term “aging” (or “senescence”) itself. What does it mean? How do you distinguish aging from non-aging? When did it arise? Is it universal, or can some organisms escape it? Is it reversible? Is it a monolithic process or a mixture of processes? What is the fundamental unit of aging: a molecule, a cell, a tissue, an organ, the organism, or all of these? Does multicellularity affect the complexity of aging? Did aging evolve? In other words, does it have a genetic basis? Is there a difference between replicative senescence, organismal senescence, and phenotypic plasticity? These are some of the questions that we hope to address in this article.