Negligible senescence

(written by Lawrence Krubner, however indented passages are often quotes)

Interesting:

This seemed to me a demographic equivalent to ‘negligible senescence’, which may be conceptualized as the extreme of slow aging in a continuum, with the other extreme of rapid senescence representing very short-lived adults. If humans did not experience aging with accelerating mortality, their median lifespan could be estimated as 1,200 years, assuming 0th order kinetics like radioactive decay, and the decay constant from the IMR of a typical 20th century population [1, pp. 28–29]. Additional criteria included maintenance of reproduction and other organ functions at levels of fully mature adults. I identified and analyzed a number of candidate species for negligible senescence, including rockfish, turtles, and bristlecone pines. Several reviewers of drafts of these chapters warned me that this concept was rash, undocumentable, and would damage my credibility, because‘nothing escapes aging’.

Fair enough! For at that time, few if any had challenged William D. Hamilton’s 1966 brilliant analysis of population reproduction and mortality during aging, ‘The moulding of senescence by natural selection’, which mathematically investigated how natural selection acts on age-specific survival and fecundity, with arguments based on the widely accepted Euler-Lotka model for population growth [7]. Hamilton’s highly influential model indicates for all sexually reproducing species that ‘… phenomena of senescence will tend to creep in’. The rate of senescence is made explicitly scalable, varying by the intensity of Darwinian selection for the reproductive contribution (reproductive value), which commonly declines with age because of two factors: reproductive (physiological) senescence and the ever diminishing sur- vival to later ages in all populations. Natural selection acts on life expectancy through the reproductive schedule, and by implication on the schedule of aging. In essence, the lifespan and pattern of aging is under natural selection for a sufficient proportion of the population to survive just long enough with sufficiently slow somatic aging to propagate the next generation. During the next 4 decades, the Hamilton model has had major sway on biogerontology through further mathematical developments of the Euler-Lotka model [8, 9] and experimental studies with artificial selection for the reproductive schedule in studies led by Michael Rose [10–12]. Lifespans (mean, maximum) and both Gompertz parameters responded to artificial selection for the reproductive schedule in outbred lab fly populations within about 10 generations [10, 12, 13]. These powerful effects are reversible, and are attributed to changes in the frequency of existing alleles without fixation. This front of biogerontological research defined a new era in theory and experiment, by showing that the schedules of aging and lifespans were highly plastic and influenced by existing genetic variation in natural populations, as well as by induced mutations.

To find further candidates for negligible senescence, I organized a series of meetings supported by the NIA and the Ellison Medical Foundation: the Workshops on Negligible Senescence (WONS-1, 1997; WONS-2, 1999) and the Symposia on Slow Aging (SOSA-1, 2000; SOSA-2, 2003). The SOSA proceedings, published as special issues of Experimental Gerontology [14, 15], compile a broad range of eukaryotes from three kingdoms (fungi, animals, and plants). I also reviewed evidence that negligible senescence is recurrent in life history evolution in a separate article [16]. I also outline here several paths to adult mortality rate decreases that are at work in postmaturational aging of sexually reproducing species: (a) individual learning to avoid predation and nutritional deficits; (b) somatic growth, which may also improve survival in competition; (c) increased adaptive immunity to pathogens, in which survivors have greater resistance, and, lastly and less likely, (d) increased somatic repair and regeneration, which might derive from postmaturational changes in gene expression that are independent of (a), (b), and (c).

Concurrently, further theory is being developed. Since 2000 at the Max Planck Institute for Demography in Rostock, James Vaupel, Annette Baudisch and colleagues have reexamined the Hamilton paper and argue from different assumptions and parameterizations that senescence was not inevitable under natural selection. These arguments were developed in two journal articles [17, 18] and in Baudisch’s monograph ‘Inevitable Aging?’ [19]. It is proposed that species with indeterminate growth with continuing increase in reproductive capacity after maturity might show negative senescence with decreasing adult mortality rates [17, 19, p. 8]. Candidate organisms include perennial trees and modular organisms like sponges which can reproduce both sexually and asexually, but also sexually reproducing vertebrates that continue somatic growth after maturation, like fish and turtles [16]. These new developments based on the Lotkamodel are controversial. Rose et al. [9] briefly comment in a penetrating review of Hamilton’s theory that the Rostock Group models are ‘interesting for life history theory [but not applicable] to Hamiltonian theories’. The terms of engagement need to be developed for debating these contending views. We need several high-level symposia and special journal issues to unfold the issues with greater participation by the experimentalist community. Meanwhile, it is timely to update two of the candidates for negligible senescence discussed at WONS and SOSA, turtles and rockfish. I consider their relevance to the naked mole-rat, a new long-lived model, and to human centenarians, and briefly link these data to the current discussions of how to achieve negligible senescence for humans at large.