Tyrannosaur ageing

Rate of ageing in tyrannosaurs was calculated from parameters of Weibull functions fitted to survival curves based on the estimated ages at death of fossilized remains. Although tyrannosaurs are more closely related to birds than to mammals, they apparently aged at rates similar to mammals of comparable size. Rate of growth in body mass of tyrannosaurs was similar to that of large mammals, and their rates of ageing were consistent with the estimated extrinsic mortality, which is strongly correlated with the rate of ageing across birds and mammals. Thus, tyrannosaurs appear to have had life histories resembling present-day large terrestrial mammals. Rate of ageing in warm-blooded vertebrates appears to be adjusted in response to extrinsic mortality and potential lifespan, independently of both physiological and developmental rates. However, individuals in species with the slowest rates of ageing suffer the highest proportion of ageing-related mortality, hence potentially strong selection to further postpone senescence. Thus, the longest observed lifespans in birds, tyrannosaurs and mammals might be close to the maximum possible.     

Theories of ageing

Ageing is a universal, intrinsic, progressive and deleterious process. Understanding it is of major interest to scientist, physicians as well as to the general population. Critical to this understanding is to formulate comprehensive theories of aging with high predictive and explanatory power. More than 300 theories have been postulated and are reviewed here. The free radical theory of ageing is one of the most prominent and well studied. It was further developed by one of us (JM) in what has become known as the mitochondrial theory of ageing. These theories provide new experimental approaches to further develop our understanding of the phenomenon of ageing.     

Intrauterine programming of ageing

Ageing is an unavoidable corollary to being alive; the most intuitive interpretation of ageing being that it is the consequence of progressive body degeneration. In agreement with this, current models propose that ageing occurs through a stepwise accumulation of DNA damage, which ultimately limits the regenerative capacity of tissues. On the other hand, there is increasing evidence that fetal distress can influence the development of disease in adult life, a phenomenon known as ‘intrauterine programming’. The extent to which an intrauterine exposure to DNA damage can compromise lifespan remains unclear. My group has recently generated a murine model of a human syndrome linked to defective DNA repair and observed that these animals age prematurely, but the accumulation of DNA damage is restricted mostly to the embryonic period. Here, I discuss the implications of this finding and propose that ageing can be influenced by fetal distress.     

Chronodisruption and ageing

Modern life leads to a more active nocturnal lifestyle, reduced sleep hours and sometimes abrupt shifts across time zones (such as jet lag and shift work) that generate chronodisruption (CD) which can result in premature ageing. CD is defined as a significant disturbance of the internal temporal order of biochemical, physiological and behavioural circadian rhythms. Epidemiological studies show that CD induced by shift work, chronic jet lag, social jet lag and excessive exposure of bright light at night is associated with an increased incidence of metabolic syndrome, cardiovascular disease, cognitive and affective impairment, sleep disorders, some cancers and premature ageing. CD may be the result of disturbances in different components of the circadian system (central pacemaker and peripheral oscillators, inputs to central clock, mainly due to visual deficiencies, and output signals from the pacemaker and oscillators). Exposure to different synchronizers (light, meal times, physical and social activities) with a regular pattern results in a chronoenhacement that can prevent age-related CD.     

Endocrine regulation of ageing

Over the past 15 years it has become clear that mutations in genes that regulate endocrine signalling pathways can prolong lifespan. Lifespan can be increased by altered endocrine signalling in a group of cells or a single tissue, which indicates that crosstalk between tissues functions to coordinate ageing of the organism. These endocrine pathways might serve as targets for the manipulation of the ageing process and prevention of age-related diseases.     

Potential biomarkers of ageing

Life span in individual humans is very heterogeneous.Thus, the ageing rate, measured as the decline of functional capacity and stress resistance, is different in every individual. There have been attempts made to analyse this individual age, the so-called biological age, in comparison to chronological age. Biomarkers of ageing should help to characterise this biological age and, as age is a major risk factor in many degenerative diseases,could be subsequently used to identify individuals at high risk of developing age-associated diseases or disabilities.Markers based on oxidative stress, protein glycation,inflammation, cellular senescence and hormonal deregulation are discussed.     

Pathophysiology of ageing.

Ageing is characterized by a gradual decline in organ functional reserves which reduces the ability to maintain homeostasis under conditions of stress. Introduction of cell culture and molecular biology techniques has provided new experimental tools for the analysis of ageing at the molecular level. During ageing progressive degeneration of cells and loss of regenerative capacity are enhanced and with time the alterations caused by them ultimately lead to death. In this paper the current knowledge of the mechanisms of ageing is summarized.     

Glyoxalase in ageing

The glyoxalase system has been studied since 1913. The biochemical function of this enzymatic system is the metabolism of reactive dicarbonyl metabolites, glyoxal and methylglyoxal, to less reactive products. In the last decade research has shown that methylglyoxal is the precursor of quantitatively important damage to the proteome and genome, forming mainly hydroimidazolone and imidazopurinone adducts in protein and DNA respectively. The aim of this article is to review the evidence of the involvement of the glyoxalase system in ageing and role of glyoxalase in future research into healthy ageing-mainly in mammalian systems for insights into consequences and interventions in human health. Protein and DNA damage by glyoxalase system substrates is linked to dysfunction of proteins susceptible to dicarbonyl modification-the dicarbonyl proteome, and DNA instability and mutation. A component of the glyoxalase system, glyoxalase 1, is a gene with expression influential on lifespan-increasing longevity being associated with increased expression of glyoxalase 1. The glyoxalase 1 gene is also a site of copy number variation in both transcribed and non-transcribed regions giving rise to population variation of expression. The glyoxalase system and Glo1 expression particularly is therefore likely linked to healthy ageing.     

Immunological markers of ageing

Ageing is a process involving morphological and physiological modifications that gradually appear with time and lead to death. Given the heterogeneous nature of the process among individuals and among the different organs, tissues, and systems in the same individual, the concept of has been developed. The search for parameters that enable us to evaluate biological age--and therefore longevity--and the analysis of the efficacy of strategies to retard the ageing process are the objectives of gerontology. At present, one of the most important theories of ageing is the theory. Given that immune cell function is an excellent marker of health, we review the concepts that enable different functional and oxidative stress parameters in immune cells to be identified as markers of biological age and longevity. None of these parameters is universally accepted as a biomarker of ageing, although they are becoming increasingly important.     

The ageing surgeon

Why do some surgeons retire (or not), and perhaps more importantly, when should some surgeons retire? Interviews were conducted with 21 senior plastic surgeons to determine why plastic surgeons choose not to retire. In an effort to answer the second question (When should surgeons retire?), an analogy is constructed between surgeons and commercial airline pilots.