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Rethinking Modern Theories of Ageing and Their Classification: the Proximate Mechanisms and the Ultimate Explanations

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Piotr Chmielewski Rethinking modern theories of ageing Anthropological Review • Vol. 80(3), 259–272 (2017) Rethinking modern theories of ageing and their classification: the proximate mechanisms and the ultimate explanations Piotr Chmielewski Division of Anatomy, Department of Human Morphology and Embryology, Faculty of Medicine, Wrocław Medical University, Poland ABSTRACT: For a very long time, ageing has been an insurmountable problem in biology. The collection of age-dependent changes that render ageing individuals progressively more likely to die seemed to be an in- tractable labyrinth of alterations and associations whose direct mechanisms and ultimate explanations were too complex and difficult to understand. The science of ageing has always been fraught with insuperable problems and obstacles. In 1990, Zhores Medvedev presented a list of roughly 300 different hypotheses to illustrate this remarkable complexity of the ageing process and various approaches to understanding its mechanisms, though none of these hypotheses or aspect theories could be the general theory of senescence. Moreover, in the light of current data some of these ideas are obsolete and inapplicable. Nonetheless, the misconception that there are hundreds of valid theories of ageing persists among many researchers and authors. In addition, some of these obsolete and discarded hypotheses, such as the rate of living theory, the wear and tear theory, the poisoning theory, or the entropy theory still can be found in today’s medical text- books, scientific publications aimed at the general public, and even in scientific writing. In fact, there are only several modern theories of ageing supported by compelling evidence that attempt to explain most of the data in current gerontology. These theories are competing to be a general and integrated model of ageing, making it unlikely that all of them could be true. This review summarises briefly several selected modern theories of senescence in the light of the contemporary knowledge of the biological basis for ageing and current data. KEY WORDS: ageing, gerontology, programmed ageing, quasi-programmed ageing, senescence, stochastic ageing, theories of ageing the ultimate explanations), thereby ad- Introduction dressing the question “Why did ageing evolve?” and those which concentrate on Traditionally, theories of biological age- proximate mechanisms, such as genes ing have been classified into two cat- and other molecular factors, that directly egories, i.e. those which explain the drive the ageing process (i.e. the proxi- evolutionary origin of senescence (i.e. mate explanations), thereby answering Review Article Received: July 4, 2017; Accepted for publication: August 10, 2017 DOI: 10.1515/anre-2017-0021 © 2017 Polish Anthropological Society 260 Piotr Chmielewski the question “How do we age?”. The longer current (Rattan 2006), this dual- first group of theories was divided into ism lingers on as it illustrates the core deterministic models that explain ageing of the long-running dispute among ger- as an atavistic, programmed, and altru- ontologists, which is known as the great istic process that is driven by hundreds conundrum in gerontology (cf. Kirkwood or thousands of genes and molecular and Melov 2011; Skulachev 2011; 2012; factors to purposefully eliminate older 2013). Interestingly, some authors sug- individuals from the population through gest that these two fiercely competing higher levels of natural selection, chief- theories “are not necessarily mutually ly group selection and evolvability at the exclusive” (Sergiev et al. 2015) as real population level (Skulachev 1997; Longo ageing can vary across species and the et al. 2005; Skulachev and Longo 2005), build-up of random molecular damage and stochastic models that explain age- or the decreased capacity for repair and ing as a completely passive and non-pro- maintenance of the body can be accelerat- grammed process that is driven by the ed by programmed aspects of senescence gradual accumulation of random molecu- whose traces and signalling pathways lar and cellular damage that is non-adap- become more and more evident thanks tive and not programmed since it is defi- to recent research into the genetics and nitely non-adaptive at the levels where epigenetics of ageing. natural selection takes place according to Unlike in the case of evolutionary the selfish gene theory (Kirkwood 2005). explanations or at least the milestones Some of the proponents of deter- (Weismann 1889; Medawar 1952; Wil- ministic models of ageing opine that liams 1957; Kirkwood 1977), a surpris- Dawkins’ theory is definitely specious, ingly large number of hypotheses related but some of these deterministic theories to the proximate mechanisms and aspects are based on flimsy argumentation (e.g. of ageing have been put forward. Indeed, entropy cannot be the real cause of age- ageing used to be an insurmountable ing, hence the theory of molecular entro- problem in biology for a long time (Holli- py is definitely invalid, while molecular day 2006; Hayflick 2007) since the collec- entropy is caused by the fact that living tion of age-dependent changes that ren- systems have built-in mechanisms that der ageing individuals progressively more actively resist entropy which tend to fal- likely to die seemed to be an intractable ter and fail in late ontogeny, and thus the labyrinth of alterations and associations causes of molecular entropy are of differ- whose direct mechanisms and ultimate ent nature) and highly speculative mod- explanations were too complex and diffi- els of the evolution of senescence such cult to follow. Thus, the science of ageing as group selection and evolvability. The has always been fraught with insuperable vast majority of researchers and scholars problems and obstacles. Edward Schnei- do not support such a view on the evolu- der, a distinguished American gerontolo- tion of senescence, which does not mean gist, quipped: “If you think that cancer is that it is utterly meaningless and without complicated, look at ageing”. Indeed, the some merit. ageing process is immensely complex and Although the above-mentioned cat- multifaceted. It is far more complex than egorization of theories of ageing into cancer. It was a Russian biogerontologist, programmed and stochastic models is no Zhores Medvedev (1990), who compiled Rethinking modern theories of ageing 261 a list of over 300 different hypotheses of general and integrated model of ageing, varying kinds to illustrate this remarka- making it unlikely that all of them could ble complexity of the ageing process and be true. This review summarises briefly various approaches to understanding its some of these modern theories of biolog- mechanisms, though none of these work- ical ageing in the light of new data and ing hypotheses or aspect theories could the contemporary knowledge of the bio- be labelled as the theory of ageing (Rat- logical basis for ageing. tan 2006). Moreover, some of them are now obsolete in the light of current data Programmed ageing: altruistic on the biological basis for ageing. Never- theless, the misconception that there are suicide through slow more than 300 valid theories of ageing “phenoptosis” or numerous valid theories and the sci- ence of ageing has not made any progress Ageing is arguably the most familiar as- since this list was presented still persists pect of ontogenetic development and among many authors and researchers. the latter process is tightly controlled In addition, some of these outdated and and programmed. Moreover, the ageing discarded hypotheses, such as the rate of process involves a predictable regulari- living theory proposed by Pearl, the early ty and reproducibility of age-dependent version of the wear and tear theory, Rub- changes in numerous morphological and ner’s theory, Mechnikov’s theory, the poi- physiological characteristics which occur soning theory, the entropy theory, and so with advancing age in all ageing individ- forth still can be found in today’s medical uals within a given species, which makes textbooks, scientific publications aimed at it rather improbable that all these altera- the general public, and scientific writing. tions depend on random, i.e. stochastic, In fact, there are only several modern factors. Therefore, since time immemo- theories of ageing supported by com- rial ageing has been perceived as pro- pelling evidence that attempt to explain grammed. This group of explanations is most of the data in current gerontolo- very old and extremely widespread, es- gy, including findings from the genetics pecially among non-specialists and new- and epigenetics of ageing and longevity, comers to the field of biogerontology. the underlying causes of sex differences It was August Weismann (1889) who in healthspan and lifespan, the effects first introduced the idea that a group of calorie restriction in animal models, of ageing and dying organisms would the effects of antioxidants on health have a fitness advantage over a group of and longevity, the mysterious effect of non-ageing and immortal organisms be- hormesis, and the links with age-related cause older, ill, and worn-out individuals diseases like cancer, cardiovascular dis- are not only valueless but also harmful to ease (CVD), and type 2 diabetes (for a the group from an evolutionary point of review, see Harman 2006; Rattan 2006; view. Therefore, although death was not Jin 2010; Sikora 2014; Kochman 2015; a primary necessity, it has become a sec- Lipsky and King 2015; Sergiev et al. ondarily
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