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From Gerontology to Geroscience: a Synopsis on Ageing

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From Gerontology to Geroscience: a Synopsis on Ageing From gerontology to geroscience: a synopsis on ageing Piotr Paweł Chmielewski Anthropological Review • Vol. 83(4), 419–437 (2020) From gerontology to geroscience: a synopsis on ageing Piotr Paweł Chmielewski Division of Anatomy, Department of Human Morphology and Embryology, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland ABSTRACT: Biological ageing can be tentatively defined as an intrinsic and inevitable degradation of biological function that accumulates over time at every level of biological organisation from molecules to populations. Senescence is characterised by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. With advancing age, all components of the human body undergo these cumulative, universal, progressive, intrinsic and deleterious (CUPID) changes. Although ageing is not a disease per se, age is the main risk factor for the development of a panoply of age-related diseases. From a mechanistic perspective, a myriad of molecular processes and components of ageing can be stud- ied. Some of them seem especially important and they are referred to as the hallmarks of ageing. There is compelling evidence that senescence has evolved as an emergent metaphenomenon that originates in the difficulty in maintaining homeodynamics in biological systems. From an evolutionary perspective, senes- cence is the inevitable outcome of an evolutionarily derived equilibrium between the amount of resources devoted to somatic maintenance and the amount of resources devoted to sexual reproduction. Single-tar- get, single-molecule and disease-oriented approaches to ageing are severely limited because they neglect the dynamic, interactive and networking nature of life. These limitations notwithstanding, many authors promote single-target and disease-oriented approaches to senescence, e.g. repurposed drugs, claiming that these methods can enhance human health and longevity. Senescence is neither a disease nor a monolithic process. In this review, the limitations of these methods are discussed. The current state of biogerontology is also summarised. KEY WORDS: age, ageing, age changes, biogerontology, gerontology, health, senescence Introduction get where the pieces were’, but Death restores them to their place saying: ‘But I haven’t for- In The Seventh Seal by Ingmar Bergman, gotten’ and ‘No one escapes me’. Death asks Antonius: ‘Have you tricked me?’, These excerpts express fundamental and the knight replies: ‘Of course. You fell truths about human life and existence. into the trap’. On another occasion, Antonius Death is inevitable. Nature carefully knocks the chess pieces over and says: ‘I for- keeps its secrets, allowing us to wonder Original Research Article Received: November 18, 2020; Revised: November 29, 2020; Accepted: December 1, 2020 DOI: 10.2478/anre-2020-0029 © 2020 Polish Anthropological Society 420 Piotr Paweł Chmielewski at its wonders. Like Antonius, we will of mortality. Longevity is a long duration never stop asking questions. Playing of life or just the length of life (Carnes chess with death, we can win a single 2011; Chmielewski et al. 2016b). Lon- battle, but does this mean that human gevity is considered a multifactorial ageing is not inevitable? trait that is determined by genetic back- In this review, I summarise the cur- ground, epigenetic alterations, the en- rent knowledge of ageing based on my vironment and lifestyle-related factors research and experience (Chmielewski such as diet, nutrition and behaviour. and Borysławski 2012, 2016; Chmielews- ki et al. 2015, 2016a, 2016b, 2017; Ch- When human ageing begins mielewski 2016, 2017, 2018, 2019, 2020a, 2020b; Chmielewski and Str- There has been considerable debate on zelec 2018, 2020). Currently, the world when biological ageing begins: at birth, of biogerontologists is divided into two conception or parental gamete forma- parties: one group believes that human tion (Milne 2006; Kinzina et al. 2019; ageing is something similar to a disorder Cohen et al. 2020b). Biochemists and that can be treated with drugs, whereas geneticists often consider ageing as the the second group considers ageing as a result of the accumulation of molecular continuum of life that is neither a treat- and cellular damage. The idea that the able condition nor a monolithic process. ageing process commences early in on- Many biogerontologists believe that age- togeny is grounded in the view that DNA ing is treatable (de Grey et al. 2002; Bla- damage accumulation most likely begins gosklonny 2018) or curable (Skulachev at parental gamete formation (Bocklandt 2011; Skulachev and Skulachev 2017). et al. 2011; Horvath 2013; Kinzina et al. In this article, arguments in favour of the 2019). Furthermore, senescent cells ac- opposite viewpoint are presented. cumulate in the body throughout ontog- eny and they can contribute to organis- Ageing, lifespan and longevity mal senescence (Franceschi and Campisi 2014; Sikora et al. 2018). On the other Biological ageing can be defined as an hand, meaningful impacts of cellular se- ‘intrinsic and inevitable degradation of nescence are primarily later in life, i.e. bio logical function that accumulates over after ELS. Moreover, critical arguments time at every level of biological organi- have posited that growth, development sation from molecules to populations’ and maturation cannot be understood (Carnes 2011) or a ‘progressive loss of as ageing (Kaczmarek and Szwed 1997; function and fitness, which occurs during Rattan 2006; Carnes 2011; Chmielews- the extended period of survival beyond ki 2017; Kaczmarek and Wolański 2018; the essential lifespan (ELS)’. Lifespan is Arking 2019). defined as an individual’s observed dura- Thus, making a distinction between tion of life. Life expectancy at birth (e0) is developmental changes, which are pro- a key term that denotes the average num- grammed and adaptive, and age-chang- ber of years newborns may be expected es, which are non-programmed and to live under the death rates that prevail non-adaptive, would further our under- at different ages in a given population. standing of ageing dynamics. In 1959, Life expectancy is an important measure Strehler proposed five criteria, i.e. cumu- From gerontology to geroscience: a synopsis on ageing 421 lative, universal, progressive, intrinsic use the term homeodynamics (Lloyd et al. and deleterious (CUPID) changes, that 2001). It is important to note that terms must all be satisfied in order to assign like ‘dynamic homeostasis’ are errone- a given change in biological structure or ous as they imply that there is also ‘static function to senescence (Carnes 2011; homeostasis’, while homeostasis (in all Arking 2019). Nevertheless, it is of note biological systems) is understood as the that physiological decline commences dynamic interplay between external influ- early in human ontogeny. Therefore, it ences that may contribute in altering an is reasonable to predict that the accumu- organism’s internal environment and the lation of molecular damage starts early internal control mechanisms that oppose (Kinzina et al. 2019; Cohen et al. 2020b). such changes. Thus, adding the adjective Ageing is heterochron, meaning that dif- ‘dynamic’ to the term that refers to a dy- ferent biological systems begin to age at namic process makes little sense (Cohen different times. The ageing process also 2016). bears similarities with heterotrop, as age changes in different biological systems Healthy ageing: from disease- may follow different patterns. For ex- ample, the skin, vasculature and kidneys oriented to health-oriented begin to age relatively early, whereas approaches physiological brain ageing occurs at later stages of ontogeny. In fact, older adults Biological ageing occurs in spite of com- experience ageing at different rates, and plex processes and mechanisms for so- even in the same person different organs matic maintenance, repair and defence age at varying rates. (Rattan 2013). Since all molecular pro- cesses in biological systems are regulated Understanding ageing: the by genes and gene products, discovering ‘genes for ageing’, i.e. gerontogenes sensu concept of homeodynamics stricto, has been a popular theme in ger- ontology. To date, hundreds of putative Unlike non-living objects, living organ- gerontogenes have been identified. Nev- isms are able to respond, to counteract ertheless, it has been established that and to adapt to the internal and exter- gerontogenes sensu stricto do not exist, nal factors. The internal conditions of and there is no genetic programme spe- biological systems are not permanently cifically to cause ageing (Kirkwood 2005; fixed and they are not ‘at equilibrium’. Kowald and Kirkwood 2016). If ageing The notion of ‘stability through constan- were genetically programmed, or at least cy’ does not sufficiently take into ac- quasi-programmed, it could be treat- count the dynamic nature of information ed like a disease (Skulachev 2011; Bla- and interaction networks that underlie gosklonny 2018). Instead, ageing is an the inherent complexity of biological emergent metaphenomenon. Although systems. Given that living organisms are ‘ageing as a disease’ label can attract dynamic entities in constant flux, it can the attention of investors, it totally dis- be argued that the biological term homeo- regards the accumulated research in the stasis is problematic (Witkowski 2009). field. Numerous sound arguments have Therefore, it would be more judicious to been advanced against the idea
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