Contemporary views on human aging and longevity

Abstract

Aging is currently stimulating intense interest of both researchers and the general public. In developed countries, the average life expectancy has increased by roughly 30 years within the last century, and human senescence has been delayed by around a decade. Although aging is arguably the most familiar aspect of human biology, its proximate and ultimate causes have not been elucidated fully and understood yet. Nowadays there are two main approaches to the ultimate causes of aging. These are deterministic and stochastic models. The proximate theories constitute a distinct group of explanations. They focus on mechanistic causes of aging. In this view, there is no reason to believe that there is only one biological mechanism responsible for aging. The aging process is highly complex and results from an accumulation of random molecular damage. Currently, the disposable soma theory (DST), proposed by Thomas Kirkwood, is the most influential and coherent line of reasoning in biogerontology. This model does not postulate any particular mechanism underpinning somatic defense. Therefore, it is compatible with various models, including mechanistic and evolutionary explanations. Recently, however, an interesting theory of hyper-function of mTOR as a more direct cause of aging has been formulated by Mikhail Blagosklonny, offering an entirely different approach to numerous problems and paradoxes in current biogerontology. In this view, aging is quasi-programmed, which means that it is an aimless continuation of developmental growth. This mTOR-centric model allows the prediction of completely new relationships. The aim of this article is to present and compare the views of both parties in the dispute, based on the results of some recent experimental studies, and the contemporary knowledge of selected major aspects of human aging and longevity

The relationship between adult stature and longevity: tall men are unlikely to outlive their short peers – evidence from a study of all adult deaths in Poland in the years 2004–2008

“…Like the processes of graying hair and wrinkle formation, lifespan does not measure the rate of aging (Kowald 2002;Heward 2010). The rates and measures of survival, such as all-cause mortality, life expectancy, and longevity, do not correspond to each other and provide different information (Chmielewski et al 2016a). Likewise, healthspan does not correspond to lifespan.…”

“…It has previously been established that body height is a good and reliable proxy for health status at both progressive and regressive stages of ontogeny, and tallness is believed to be associated with better health, higher SES, reduced all-cause mortality, and longer life expectancy (Waaler 1984;Nyström Peck and Vågerö 1987;Holl et al 1991;Allebeck and Bergh 1992;Elo and Preston 1992;Herbert et al 1993;Power and Matthews 1997;Silventoinen et al 1999;Cavelaars et al 2000;Jousilahti et al 2000;Lawlor et al 2002;2004;Engeland et al 2003;Kemkes-Grottenthaler 2005;Song and Sung 2008;Austad 2010;Kirkwood 2010;Özaltin 2012;Chmielewski et al 2015a;2015b;2016a;2016b;Perkins et al 2016). The better health status, nutrition, environmental conditions, medical care, and prophylaxis during the progressive development, the taller the individuals are in a given population.…”

Association of serum bilirubin with longevity: Evidence from a retrospective longitudinal study and cross-sectional data

“…the mechanisms associated with gender gap in longevity such as the genetic and molecular benefits from the homogametic state, higher levels of estrogens, lower levels of testosterone, the cessation of reproduction, etc.). Therefore, the beneficial effects of elevated STB levels on long-term survival are more pronounced and perspicuous in older men since their survival is more dependent on such a single factor compared to women whose longer lifespan is ensured by other adaptive mechanisms linked to the gender gap in longevity, including the molecular mechanisms of ROS production and scavenging, the insulin/IGF-1 signaling pathway, hyperfunction of mTOR, the hormonal milieu, telomere length and attrition, and other processes that are responsible for longer life expectancy in women (for a review, see Rincon et al 2005;Jiang et al 2007;Kirkwood 2010;Borysławski and Chmielewski 2012;Chmielewski 2012;2017;Regan and Partridge 2013;Chmielewski and Borysławski 2016;Chmielewski et al 2016b).…”

The dynamic nature of ageing: novel findings, therapeutic avenues and medical interventions

“…It has been hypothesised that mTOR is a key sensor of various cellular signals, including energy level, oxygen, nutrients, stress and growth and a central hub of nutrient signalling and cell growth, which plays an active role in development and ageing and might contribute to age-related diseases (Kennedy and Lamming 2016;Campisi et al 2019;Kim and Guan 2019). In late ontogeny, mTOR becomes 'hyperactive', which might contribute to ageing (Blagosklonny 2008; Chmielewski et al 2016a). It is believed that also other factors that lead to an upregulation of protein translation and increased reactive oxygen species (ROS) production can contribute to ageing sensu lato (Zimniak 2012).…”

“…Ageing is arguably one of the most complex and difficult problems for humans to face and for science to solve (Kirkwood and Franceschi 1992; Kaczmarek and Szwed 1997;Chmielewski et al 2016a;Cohen 2016;Muntané et al 2018;Chmielewski 2019aChmielewski , 2019b. At the same time, ageing is a fascinating phenomenon that has captivated philosophers and researchers for centuries (da Costa et al 2016).…”