Within- and Between-Species Study of Extreme Longevity--Comments, Commonalities, and Goals

We, the editors of this special combined issue of the Journals of Gerontology, Series A (Biological and Medical Sciences), hope that the following papers will provide readers with fertile ground for the generation of new ideas and opportunities concerning extreme longevity research. The presentation of these varied scientific approaches to the study of a single theme will, hopefully, allow readers to explore topics outside of their own immediate areas of expertise. The contributing authors were asked to write with the aim of speaking to an audience that was likely to be unfamiliar with their research topic or methodology. Thus, they included more background and provided more context than they might when addressing fellow members of their own subdiscipline, so that researchers working in other biogerontological subdisciplines might gain insights and inspiration from work tangential to their own. The common thread throughout this issue is “extreme longevity,” but this phrase is used differently by those studying a single species versus those comparing different species. What may at first blush be perceived as a nuance is actually a key question for this special issue and for comparative biogerontology generally—namely, whether organisms achieving extreme longevity within a species versus between species do so via some common mechanisms. If mechanisms do differ between long-lived individuals within a species and long-lived species themselves, what may we learn from such a diversity of mechanistic routes to extreme longevity? Some of the research presented will elicit controversy. Already in this brief introduction, several controversial words and phrases have been introduced. As Hayflick (1) noted: “Communication in the field of biogerontology is a minefield because all of the commonly used terms have no universally accepted definitions.” Along these lines, the proper way to measure something can be a major bone of contention. For example, in their neuropathological and neuropsychological investigation of dementia among centenarians, Leonard Poon and colleagues (2) discuss how disparate reported estimates of dementia prevalence among centenarians are a consequence not only of the vicissitudes of subject selection but also of the different tools used to assess cognitive function, different cutoff measures for naming categories of dementia, and different causes of dementia in different populations. Thus, we feel it worthwhile to briefly digress and define a few terms as we use them in this editorial. These definitions are our own working definitions so that, for the duration of this paper at least, ambiguity may be avoided. It will come as no surprise to most readers that “biological aging” and “senescence(definition)” are slippery words with many somewhat conflicting definitions. For the purposes of this special issue, then, we define our terms as follows. First, borrowing very heavily from Arking (3): “Aging is a cumulative, progressive, intrinsic and deleterious alteration in physiological state which increases vulnerability and culminates in death.” This definition separates progressive increases in vulnerability from the probability of encountering specific challenges during windows of susceptibility. Second, extreme longevity is defined in one of the following ways, as appropriate: (a) an exceptionally long life span based on comparisons within a single species, (b) an exceptionally long life span based on comparisons between mutant and wild-type animals, or (c) an exceptionally long life span based on comparisons among species predicted to have similar life spans because of shared physiological measures, such as size and metabolic rate. Underlying the study of aging within or among species is the desire to improve human health and healthy longevity. Research on exceptionally long-lived individuals is guided by the hope that it will allow us to determine which genetic (and associated biological) pathways, and which environmental and stochastic factors, are key determinants. These in turn may help delineate relative risk for extreme longevity, healthy and unhealthy aging, and specific age-related diseases and syndromes. Such information could lead to more targeted and effective prevention and screening as well as specific therapeutics. No single issue of this journal could thoroughly address all of the open questions, issues, and goals of the field. Thus, this issue attempts to include a selection of interesting studies, using a variety of models, which address one or more major goals or open questions. In this issue, Bruce Carnes and colleagues (4) present their study of the effect of maternal age upon the longevity of offspring in mice. They found that older “middle-aged” female mice bore offspring with shorter life spans. There was not such an effect between older fathers and their offspring. This study affirms an association between maternal age and life span in several model organisms and argues for a trade-off between fertility and life span. In humans, however, the relationship is less clear. Some data appear consistent with this relationship (eg, see references 24–30 in [4], this issue). However, other data suggest that we have more to learn. For example, women living to extreme old age appear to remain fertile until later in life (5–8). This is consistent with relatively slower aging of the reproductive system and/or delay or avoidance of diseases that adversely affect reproduction. Thus, they are capable of having children later in life than women who don’t ultimately achieve such old ages. More research is needed on this interesting subject. The extent to which damage and repair influence the rate of aging is another topic that is often the subject of heated debate, and this led to the inclusion in this issue of work exploring another model: the naked mole rat. As explained by Grimes and colleagues (9), the naked mole rat not only lives an incredibly long period of time, nearly 10 times l