We are currently facing particular challenges related to demographic change. People are living very long lives and average life expectancy has increased considerably since the mid-20th century. Predictions are that citizens over 65 will increase from 18% of the population today to 28% in 2060. In addition, citizens over 80 years of age will increase from 5% to 12% during the same period, becoming as numerous as the young population in 2016 [1]. 

However, the increase in life expectancy has led to a decline in quality of life in the later years of life, i.e. a decrease in the period of life free of serious chronic diseases and disabilities [1; 2]. This suggests a situation characterised by an increase in age-related disability and dependency, which will have an impact not only on the well-being and quality of life of those affected, but also on the sustainability of health systems [3]. 

This scenario constitutes the real challenge: unlocking the biological secrets of ageing in order to better understand this process, which will allow the development of appropriate interventions to increase not only life expectancy but also disease-free life expectancy and decrease the medical, economic and social problems associated with older people. 

The aging process 

Aging is a very complex process and there are many definitions to describe it depending on the field. From a biological point of view, "aging is a progressive sequence of generalised, more or less common age-related changes observed in each individual of a given species" [4]. It is characterised by four postulates [5; 6]. It is universal: it must occur in all individuals of a species; intrinsic: endogenous factors cause it, although exogenous factors may modulate it; progressive: changes must occur progressively over the life span, from early adulthood to old age; and deleterious: it has negative consequences for the individual. 

Aging is not a disease: it is a physiological process that differs from disease in that disease is selective (not universal), intrinsic and extrinsic (not just intrinsic), discontinuous (not progressive) and reversible. 

Aging begins early in life, after the development of the organism. It implies that, over many years, it can be influenced by many exogenous factors (accelerators or decelerators of the rate of ageing). It can be different in different individuals, giving rise to the distinctive heterogeneity of aging. Not all individuals age at the same rate, nor do all organs of the same individual. The complexity of the aging process is the reason for the great challenge of unlocking its biological secrets. 

Aging theories 

Because aging is multifactorial, many theories attempt to explain the underlying fundamental biological processes. In 1990, Medvedev stated that there are more than 300 theories of aging and the number continues to grow [7]. This is the natural consequence of the rapid progress in our understanding of biological phenomena and the application of many new approaches and methods to gerontological research. Almost every major discovery in cell and molecular biology has generated a new family of theories of aging or new advanced versions of older theories [8]. The expectation that a truly unified or single-cause theory of ageing will emerge is unrealistic. And it is generally accepted that all the pieces of the old puzzle are not yet available [9]. However, we believe that it is possible to offer preliminary solutions to this problem by integrating several complementary classical and modern theories that offer logical explanations for the changes occurring at fundamental levels of biological organisation [6]. In fact, several authors have proposed a unified theory of aging [10; 11]. 

Thus, we can state that there are many theories to explain the phenomenon of aging, and even today the main causes of aging are not known for sure. 

Aging biomarkers 

An aging biomarker is a biological parameter of an organism that, either alone or in combination, in the absence of disease, is a better predictor of biological age and functional capacity at advanced age than chronological age [12]. The requirements for a biomarker of aging are to change progressively with age, to refer to parameters relevant to health and longevity, to be minimally invasive, to be relatively easy to determine and to be reproducible. 

Most biomarkers of aging are developed from theories of aging. In fact, most of them are related to aging-related processes and pathways. As Lopez-Otin et al. pointed out some years ago [13], parameters related to the nine hallmarks of aging should be good candidates for biomarkers of aging, if they meet the above-mentioned requirements. These parameters are genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis (and autophagy), altered nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell depletion and altered intercellular communication. In addition, oxidative stress-related parameters have also been proposed as good candidates, as they fulfil all the requirements to be biomarkers of aging [14; 15]. Other good candidates are those parameters related to the so-called inflammation process and the function of the immune system. These are known to decrease with age, and have been proposed by many scientists as possible aging biomarkers [16-18]. 

Although many processes underlying aging are known, and there are many proposed biomarkers of aging related to these processes, there are no completely reliable biomarkers of aging. Probably the best approach to a reliable biomarker of aging is one that is based on a set of several markers. For example, the "epigenetic clock" based on a dataset of DNA methylation data has allowed accurate estimates of the age of any tissue throughout the life cycle [19]. In fact, reprogramming the epigenetic clock resets the ageing clock and the organism rejuvenates [20]. 

Certainly, a challenge is to develop reliable biomarkers of aging because it allows a better understanding of the aging process and, at the same time, enables the development of appropriate interventions to delay aging and promote successful aging. 

Final remarks 

We are currently facing particular challenges related to the pursuit of healthy aging. However, the increase in life expectancy has led to a decrease in the quality of life in these later stages. This scenario constitutes the real challenge: unlocking the biological secrets of aging in order to better understand this process, which will allow the development of appropriate interventions to not only add years to life, but also life to years and to reduce the medical, economic and social problems associated with the elderly. 

In-depth understanding of the basic mechanisms involved in aging helps to better understand the aging process. Molecular mechanisms of aging play an integral and interdisciplinary role in modern science and include significant advances in areas including, among others, biomarkers of aging, senescence, proteostasis, autophagy, chromosomal alterations, dysregulation of the redox system, alterations in nutrient sensing, genetic and epigenetic changes, mitochondrial energy collapse, alterations in intercellular communication, dysregulation of stem cell function and alterations in extracellular vesicles. 

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