Potential Noninvasive Biomarkers to Assess the Aging Process

Longevity medicine: upskilling the physicians of tomorrow

The aging population worldwide is expanding at an increasing rate. By 2050, approximately a quarter of the world population will consist of the elderly. To slow down the aging process, exploration of aging biomarkers and the search for novel antiaging targets have attracted much interest. Nonetheless, because aging research is costly and time-consuming and the aging process is complicated, aging research is considered one of the most difficult biological fields. Here, providing a broader definition of aging biomarkers, we review cutting-edge research on aging biomarkers at the molecular, cellular, and organismal levels, thus shedding light on the relations between aging and telomeres, longevity proteins, a senescence-associated secretory phenotype, the gut microbiota and metabolic patterns. Furthermore, we evaluate the suitability of these aging biomarkers for the development of novel antiaging targets on the basis of the most recent research on this topic. We also discuss the possible implications and some controversies regarding these biomarkers for therapeutic interventions in aging and age-related disease processes. We have attempted to cover all of the latest research on aging biomarkers in our review but there are countless studies on aging biomarkers, and the topic of aging interventions will continue to deepen even further. We hope that our review can serve as a reference for better characterization of aging and as inspiration for the screening of antiaging drugs as well as give some clues to further research into aging biomarkers and antiaging targets.

Striving towards excellence in research on biomarkers.

Aging is a natural process defined by the gradual, time-dependent decline of biological and behavioural functions, for which individuals of the same chronological age show variability. The capacity of biological systems to continuously adjust for optimal functioning despite ever changing environments is essential for healthy aging, and variability in these adaptive homeostatic mechanisms may reflect such heterogeneity in the aging process. With an ever-increasing aging population, interest in biomarkers of aging is growing. Although no universally accepted definition of biomarkers of healthy aging exists, mediators of homeostasis are consistently used as measures of the aging process. As important sex differences are known to underlie many of these systems, it is imperative to consider that this may reflect, to some extent, the sex differences observed in aging and age-related disease states. This chapter aims to outline sex differences in key homeostatic domains thought to be associated with the pathophysiology of aging, often proposed as biomarkers of aging and age-related disease states. This includes considering sex-based differences and hormonal status with regards to the gonadal and adrenal endocrine systems and immune function.

As the overall life expectancy and aging of society increase, the number of diseases, disabilities and mortality increases, which creates a serious medical and social problem. Therefore, the search for effective and safe for the body ways to reduce biological age and slow down the aging process. Physical activity can compensate for the effects of aging on self-efficacy. Massage in its effect on the body is close to physical activity, improves well-being, blood circulation, metabolism, lymph outflow and tissue drainage. It is an more effective and practically safe method of therapy than drugs. Massage has significant preventive potential and is one of the promising non-drug means of reducing biological age and prevention of premature aging. The purpose of the work. Evaluate the effectiveness of using different types of massage to reduce biological age in relatively healthy people from 30 to 69 years. Research methods. The study involved 78 people (67 women and 11 men), who were divided into three groups. A course of massage of 10 procedures every other day of the neck area and thoracic back was performed in order to prevent premature aging and reduce biological age. Cryomassage was performed with the help of cryopackets, and vacuum massage was performed on a Cerri device (Italy). The control group included patients who did not receive massage. Before and after therapy, a number of indicators were determined – biomarkers of aging and biological age. Results of work. Cryomassage and vacuum massage have been shown to effectively improve a number of biomarkers of aging: lower systolic, diastolic and pulse blood pressure, increase lung vital capacity and expiratory respiration time, improve balance, improve self-esteem and improve self-esteem. Conclusions. Both types of neck massage contribute to the reduction of biological age and prevention of premature aging in the studied patients, in contrast to the control group.

While all organisms age, our understanding of how aging occurs varies among species. The aging process in perennial plants is not well-defined, yet can have implications on production and yield of valuable fruit and nut crops. Almond exhibits an age-related disorder known as non-infectious bud failure (BF) that affects vegetative bud development, indirectly affecting kernel yield. This species and disorder present an opportunity to address aging in a commercially relevant and vegetatively propagated perennial crop. The hypothesis tested in this study was that relative telomere length and/or telomerase reverse transcriptase (TERT) expression can serve as biomarkers of aging in almond. Relative telomere lengths and expression of TERT, a subunit of the enzyme telomerase, were measured via qPCR methods using bud and leaf samples collected from distinct age cohorts over a two-year period. Results from this work show a marginal but significant association between both relative telomere length and TERT expression, and age, suggesting that as almonds age, telomeres shorten and TERT expression decreases. This work provides information on potential biomarkers of perennial plant aging, contributing to our knowledge of this process. In addition, these results provide opportunities to address BF in almond breeding and nursery propagation.

Exploring geriatricians' perspectives on aging biomarkers: A reflexive thematic analysis.

Strategy for identifying biomarkers of aging in long-lived species.

Chronic inflammation is a major biological mechanism underpinning biological ageing process and age-related diseases. Inflammation is also the key response of host defense against pathogens and tissue injury. Current opinion sustains that during evolution the host defense and ageing process have become linked together. Thus, the large array of defense factors and mechanisms linked to the NF-κB system seem to be involved in ageing process. This concept leads us in proposing inductors of NF-κB signaling pathway as potential ageing biomarkers. On the other hand, ageing biomarkers, represented by biological indicators and selected through apposite criteria, should help to characterize biological age and, since 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. In this report, some inflammatory biomarkers will be discussed for a better understanding of the concept of biological ageing, providing ideas on eventual working hypothesis about potential targets for the development of new therapeutic strategies and improving, as consequence, the quality of life of elderly population.

The aging process is a complex and dynamic phenomenon influenced by genetic, environmental, and biochemical factors. One of the key contributors to aging and age-related diseases is oxidative stress, resulting from an imbalance between the generation of reactive oxygen species (ROS) and the efficiency of antioxidant defense systems. In this review, we introduce the concept of the oxidative stress complexity—a network encompassing ROS-generating systems, enzymatic and non-enzymatic antioxidants, and genetic determinants that collectively shape redox homeostasis. Emerging research highlights the significant influence of genetic variability on the activity and expression of selected and most examined antioxidant enzymes, including superoxide dismutase (SOD), paraoxonase 1 (PON1), catalase (CAT), and glutathione peroxidase (GPX), thereby modulating individual susceptibility to oxidative damage, disease onset, and the pace of aging. Particular attention is paid to the interplay among oxidative stress, chronic inflammation, and metabolic dysfunction in the pathogenesis of various age-related disorders. By integrating findings from molecular studies, clinical research, and population genetics, we discuss the diagnostic and prognostic potential of antioxidant enzymes as biomarkers of aging and explore strategies for redox-modulating interventions. Understanding these interrelations is essential for identifying biomarkers of biological aging and developing personalized strategies aimed at promoting healthy aging and reducing the risk of chronic disease.

The question of why we age and finally die has been a central subject in the life, medical, and health sciences. Many aging theories have proposed biomarkers that are related to aging. However, they do not have sufficient power to predict the aging process and longevity. We here propose a new biomarker of human aging based on the mass‐specific basal metabolic rate (msBMR). It is well known by the Harris–Benedict equation that the msBMR declines with age but varies among individual persons. We tried to renormalize the msBMR by primarily incorporating the body mass index into this equation. The renormalized msBMR (RmsBMR) which was derived in one cohort of American men (n = 25,425) was identified as one of the best biomarkers of aging, because it could well reproduce the observed respective American, Italian, and Japanese data on the mortality rate and survival curve. A recently observed plateau of the mortality rate in centenarians corresponded to the lowest value (threshold) of the RmsBMR, which stands for the final stage of human life. A universal decline of the RmsBMR with age was associated with the mitochondrial number decay, which was caused by a slight fluctuation of the dynamic fusion/fission system. This decay form was observed by the measurement in mice. Finally, the present approach explained the reason why the BMR in mammals is regulated by the empirical algometric scaling law.

Allogeneic Hematopoietic Cell Transplantation Causes Accelerated Aging Both of the Hematopoietic and Somatic Systems

It is a challenging task to verify and quantify potential biomarkers expressed at elevated levels in sera from cancer patients. An immunoaffinity-mass spectrometry-based approach has been developed using antibodies to enrich proteins of interest from sera followed by mass spectrometry-based quantification. Antibodies specific to the protein of interest were immobilized to hydrazide resin via the carbohydrate moiety on the Fc region of the antibody. Captured proteins were eluted, reduced, alkylated, and digested with trypsin. Peptides were analyzed by LC coupled with multiple reaction monitoring approach, and quantification was achieved by the addition of stable isotope-labeled (heavy) standard peptides. Using this methodology, we were able to achieve a linear response from 15 to 250 ng/ml for carcinoembryonic antigen (CEA), a known tumor biomarker. Moreover we observed elevated levels of CEA in sera samples from lung cancer patients that to our knowledge is the first time that circulating CEA has been detected by mass spectrometry-based analysis. This approach was further applied to potential protein biomarkers discovered from tumor cell lines and tumor tissues. A linear response was obtained from a multiplex spiking experiment in normal human sera for secretory leukocyte peptidase inhibitor (4-500 ng/ml), tissue factor pathway inhibitor (TFPI) (42-1000 ng/ml), tissue factor pathway inhibitor 2 (TFPI2) (2-250 ng/ml), and metalloproteinase inhibitor 1 (TIMP1) (430-1000 ng/ml). A replicate experiment for a single concentration value yielded a relative coefficient of variation better than 11% for TFPI, secretory leukocyte peptidase inhibitor, and TFPI2. The expression level of the proteins in lung cancer patient sera was assayed by an immunoaffinity-multiple reaction monitoring method, and the results were comparable with those obtained from ELISA. This immunoaffinity-mass spectrometry-based quantification approach thus provides a specific and accurate assay for verifying the expression of potential biomarkers in patient serum samples especially for those proteins for which the necessary reagents for ELISA development are unavailable.

The analytical review is devoted to the methodology for quantifying age-related changes, namely, the determination of biological age (BA). In contrast to the chronological age (CA), which is the same for all people born at the same time, BA can vary significantly and characterizes the rate of aging. Diagnostics of accelerated aging is of great clinical importance, as it allows predicting the development of age-related pathology. In addition, the BA calculation is used to assess various effects on the body, including geroprotectors. To calculate BA, a set of biomarkers of aging (BMA) is used. The most accurate method for determining BA is by measuring the methylation of certain genes (Horvath clock). However, this method is not available for clinical practice yet. Therefore, the development of BA models based on clinical BMS remains relevant. In addition, there is a need to assess the degree of age-related changes at the level of individual functional systems of the body (functional age). The list of BMA available for use in clinical practice is given in this review. The requirements are given that allow using the indicator of age-related changes as BMA. The main methods for calculating BV are multiple linear regression (MLR), principal component analysis (PCA), Klemera and Doubal method (KDM), and neural network analysis. The criteria for assessing the quality of the BA model are described in this review. The MLR method, due to its simplicity, is most often used in clinical practice, however, it has a significant drawback, namely, the systematic error in calculating age, which is most pronounced in the extreme age groups. The article provides a method for correcting this error developed by the authors. The methodology of using MLR to obtain a formula for determining BA from a dataset BMA is described in detail. The theoretical foundations of the use of neural network algorithms for assessing the rate of aging are presented. The use of neural networks for assessing BA has shown their high efficiency by all criteria, in particular, the absence of a systematic error inherent in MLR-based methods. Keywords: biological age, biomarkers of aging, calculation methods.

Nonenzymatic Post-Translational Modification Derived Products: New Biomarkers of Protein AgingDuring their biological life, proteins are exposed in a cumulative way to irreversible nonenzymatic post-translational modifications that are responsible for their molecular aging and generate specific by-products called »post-translational modification derived products« (PTMDPs). PTMDPs are involved in the pathogenesis of various diseases such as diabetes mellitus, renal insufficiency and atherosclerosis, and are potential biomarkers in clinical practice. Nonenzymatic glycation refers to the spontaneous binding of glucose and reducing sugars to free amino groups and is amplified by oxidative processes (referred to as »glycoxidation«). It generates many reactive by-products such as aldehydes and leads to the formation of »advanced glycation end products« (AGEs). AGEs accumulatein vivo, alter tissue organization and activate membrane receptors such as RAGE, which triggers inflammatory responses. Carbamylation is due to the binding of isocyanic acid, formedin vivoeither by spontaneous dissociation of urea or by action of myeloperoxidase on thiocyanate, and generates homocitrulline from lysine groups. Carbamylation leads to alteration of the structural and biological properties of proteins, and favors inflammation and atherosclerosis. PTMDPs may be assayed by different methods, among others LC-MS/MS or immuno assays, constitute a promising field of investigation in basic research and are potential major biomarkers in laboratory medicine.