Epidemiological and clinical studies suggest that elevated leukocyte count within the normal range can predict cardiovascular and total mortality in older adults. These findings are remarkable because this simple and common laboratory test is included in routine medical check-ups. It is well known that chronic systemic inflammation (inflammaging) is one of the hallmarks of aging and an important component of obesity-associated insulin resistance that can lead to type 2 diabetes and other health problems in both overweight individuals and elderly people. To understand the molecular mechanisms linking increased systemic inflammation with aging-associated diseases and elevated leukocyte counts in the elderly is to unravel the multiplicity of molecular factors and mechanisms involved in chronic low-grade systemic inflammation, the gradual accumulation of random molecular damage, age-related diseases, and the process of leukopoiesis. There are several possible mechanisms through which chronic low-grade systemic inflammation is associated with both higher leukocyte count and a greater risk of aging-associated conditions in older adults. For example, the IL-6 centric model predicts that this biomediator is involved in chronic systemic inflammation and leukopoiesis, thereby suggesting that elevated leukocyte count is a signal of poor health in older adults. Alternatively, an increase in neutrophil and monocyte counts can be a direct cause of cardiovascular events in the elderly. Interestingly, some authors assert that the predictive ability of elevated leukocyte counts with regard to cardiovascular and allcause mortality among older adults surpass the predictive value of total cholesterol. This review reports the recent findings on the links between elevated but normal leukocyte counts and the increased risks of all-cause, cardiovascular, and cancer mortality. The possible molecular mechanisms linking higher but normal leukocyte counts with increased risk of aging-associated diseases in the elderly are discussed here.
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 intractable 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 textbooks, 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.
Early epidemiological studies demonstrated that short stature is associated with cardiovascular disease (CVD), diabetes, lower energy intake or food deprivation during growth, poor health, and increased all-cause mortality. Nevertheless, the links between adult height and longevity become tenuous if certain confounders (e.g. BMI, SES, educational attainment, etc.) are allowed for. Furthermore, numerous studies have found that like excess weight, tallness is costly in terms of longevity in late ontogeny, and shorter people tend to outlive their taller peers, especially if they are slim and maintain a healthy diet and lifestyle. Therefore, there is currently a lack of agreement in the literature as to whether and how body height and lifespan are linked. The objective of this study was to explore the relationship between adult stature and longevity on the basis of a large sample from a population-based cohort study. Data on declared height and exact dates of birth and death were available from 480,493 men and 364,666 women who died in the years 2004-2008 in Poland. To control for secular changes, the sample was divided into fifteen birth cohorts and each group was subsequently split into five height categories using pentiles, separately for both sexes. The analysis has revealed an inverse relationship between height and lifespan in men and women. However, after controlling for secular changes in height, the relationship turned out to be very weak and linear in men, and inverted U-shaped in women. In general, taller individuals had lower age at death compared to shorter ones, and this relationship was more pronounced and consistent in men. To sum up, these findings do not comport with the traditional belief that taller individuals live longer. The role of several possible biological mechanisms pertinent to enhanced longevity in smaller individuals was emphasized, and these biological factors were discussed.
Ageing is one of the most complex and difficult problems for humans to face and for science to solve. Although human senescence was viewed as a passive and uncontrollable process of deterioration over time with little or no genetic regulation, the concept that ageing is caused by both genetic and environmental factors is now generally accepted, even though it remains difficult to distinguish between ageing sensu stricto and the effects of age-related diseases. Empirical data show that mechanisms of ageing are highly conserved during evolution. Moreover, it has been established that there are specific molecular ‘instructions’ for ageing, which suggests that a better understanding of the molecular biology of ageing will open new possibilities regarding future interventions. The complexity of ageing diminishes the possibility that any general theory will completely explain this metaphenomenon. Likewise, it is highly unlikely that any medication can stop or reverse human senescence. Nevertheless, ageing as a dynamic and malleable metaphenomenon can be modulated by a variety of influences. The concept of the shrinkage of the homeo-dynamic space with age, i.e. homeostenosis, is especially interesting and intriguing as it shows that novel therapeutic approaches and rational strategies can help delay the onset of the ageing-associated pathologies by enhancing the homeodynamic capabilities of the body. The aim of this article is to present current data from evolutionary and molecular gerontology and discuss them within the ambit of this review which is devoted to the dynamic, emergent and plastic nature of human ageing and implications for future interventions.
Understanding the proximate and ultimate causes of ageing is one of the key challenges in current biology and medicine. These problems are so important that they are sometimes referred to as the Holy Grail of biology and the Great Conundrum in biogerontology. From an evolutionary perspective, ageing is due to a failure of selection that is caused either by declining strength of selection after the onset of sexual reproduction (Medawar’s theory and Charlesworth’s model) or pleiotropic constraints (Williams’ theory). According to the disposable soma theory, which was proposed by Kirkwood and Holliday, ageing is driven by the accumulation of damage during life and failures of defensive and repair mechanisms as the more an animal expends on sexual reproduction, the less it can expend on bodily maintenance, and vice versa. Although these standard models rule out the possibility that ageing is programmed, there is no consensus about the nature of ageing within the life history in current biogerontology. Interestingly, empirical studies show that there are molecular instructions for ageing and evolutionarily conserved mechanisms for ageing, which seems inconsistent with the idea that ageing is a matter of neglect or a consequence of a failure of selection due to pleiotropic constraints. Here, selected arguments for programmed (i.e. either determined and adaptive or prearranged but non-adaptive) and non-programmed ageing are discussed. Recent advances in biogerontology that cast new light on these problems are outlined here in the context of the idea that the pace of ageing can act as an adaptation in nature, even though ageing is non-programmed and non-adaptive.
Ageing is distinct from a disease. Sound arguments have been adduced to explain that senescence cannot be understood as a pathological process. Nevertheless, this distinction is believed to be artificial (Holliday 1995), and other eminent researchers argue that the senescence-pathology dichotomy is also misleading. Recently, it has been suggested that ageing should be classified as a complex pathological syndrome or a ‘pre-disease’ that is treatable. Proponents of this new paradigm argue that: (i) modern evolutionary theory predicts that ‘although organismal senescence is not an adaptation, it is genetically programmed’, (ii) ‘insofar as it is genetically determined, organismal senescence is a form of genetic disease’ (Janac et al. 2017) and (iii) ‘ageing is something very much like a genetic disease: it is a set of pathologies resulting from the action of pleiotropic gene mutations’ (Gems 2015). Also new generations of researchers, free of these traditional shackles, come with the belief that it is time to classify ageing as a disease, as the distinction between normal dysfunction and abnormal dysfunction is not completely clear and should be abandoned. Although they marshal their arguments in a convincing manner, persuasive counterarguments can be mounted. Here, the senescence-pathology dichotomy is critically discussed. A deeper analysis of this subject reveals the underlying problem of undefined terminology in science.
There is a lack of agreement in the literature as to whether adult height depends on month of birth and whether height affects lifespan. Additionally, the relationship between stature and longevity involves conflicting findings and the results remain mixed due to several confounders, such as: year of birth, somatotype, relative body weight, genetic inheritance, diet, diseases, etc. Here, we hypothesize that the season of birth effect can also be involved in shaping the mysterious link between body height and longevity. To assess the links between month of birth, adult height, and longevity in the Polish population, data on 848,860 individuals, of whom 483,512 were men (57%) and 365,348 were women (43%), born in the years 1896-1988 and died in the years 2004-2008, were collected from the ‘PESEL’ database and signalments in the censuses obtained from identity card offices throughout Poland. ANOVA and the LSD test were performed. A significant relationship between month of birth and lifespan was found. Individuals born in autumn and winter months lived significantly longer than those who were born in the middle of the year (May). The amplitudes of lifespan were 16 months in men and 14 months in women. As expected, subjects of both sexes born in autumn and winter months were significantly shorter than their peers born around the middle of the year. In conclusion, the results of the study not only corroborate the theory of seasonal programming of longevity and support the idea that some undetermined factors from early stages of ontogeny and associated with season of birth have long-term effects on phenotype in later life in terms of adult height and longevity, but also bear out the hypothesis that month of birth can be another important confounding factor with respect to the relationship between adult height and longevity.
The connection between the rate of height loss in older people and their general health status has been well documented in the medical literature. Our study was aimed at furthering the characterization of this interrelationship in the context of health indices and mortality in a hospitalized population of Polish adults. Data were collated from a literature review and from a longitudinal study of aging carried out in the Polish population which followed 142 physically healthy inmates, including 68 men and 74 women, for at least 25 years from the age of 45 onwards. Moreover, cross-sectional data were available from 225 inmates, including 113 men and 112 women. These subjects were confined at the same hospital. ANOVA, t-test, and regression analysis were employed. The results indicate that the onset of height loss emerges in the fourth and five decade of life and there is a gradual acceleration of reduction of height at later stages of ontogeny in both sexes. Postmenopausal women experience a more rapid loss of height compared with men. The individuals who had higher rate of loss of height (≥3 cm/decade) tend to be at greater risk of cardiovascular events and all-cause mortality. In conclusion, our findings suggest that a systematic assessment of the rate of loss of height can be useful for clinicians caring for elderly people because of its prognostic value in terms of morbidity and mortality.
Longitudinal studies of aging concerning individuals with comparable lifestyle, diet, health profile, socioeconomic status, and income remain extraordinarily rare. The purposes of our ongoing project are as follows: (i) to collect extensive data on biological and medical aspects of aging in the Polish population, (ii) to determine factors affecting the rate and course of aging, (iii) to understand how aging unfolds as a dynamic and malleable process in ontogeny, and (iv) to find novel predictors of longevity. Our investigation followed 142 physically healthy asylum inmates, including 68 males and 74 females, for at least 25 years from the age of 45 years onward. Cross-sectional assessment involved 225 inmates, including 113 males and 112 females. All the patients lived for a very long time under similar and good environmental conditions at the hospital in Cibórz, Lubuskie Province. They maintained virtually the same daily schedule and lifestyle. The rate and direction of changes with age in selected anthropometric and physiological traits were determined using ANOVA, t-test, and regression analysis. There were sex differences in the rate and pattern of age-related changes in certain characteristics such as relative weight, red blood cell count, monocyte count, thymol turbidity value, systolic blood pressure, and body temperature. Body weight, the body mass index (BMI), and total bilirubin level increased with advancing age, while body height decreased with age in both sexes. In conclusion, the aging process was associated with many regressive alterations in biological traits in both sexes but the rate and pattern of these changes depended on biological factors such as age and sex. There were only few characteristics which did not change significantly during the period under study. On the basis of comparison between the pattern of longitudinal changes with aging and the pattern of cross-sectional changes with age in the analyzed traits, we were able to predict which pattern of changes is associated with longer lifespan.
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