Letter to the Editor

Improvement of biological age by physical activity

Telomerase is a reverse transcriptase that consists of the telomerase reverse transcriptase (TERT) protein and the telomerase RNA component TERC which also harbors the template region for telomere synthesis. In its canonical function the enzyme adds single-stranded telomeric hexanucleotides de novo to the ends of linear chromosomes, telomeres, in telomerase-positive cells such as germline, stem- and cancer cells. This potential biochemical activity of telomerase can be measured with the help of a telomerase repeat amplification protocol (TRAP) which often includes a PCR amplification due to the low abundance of telomerase in most cells and tissues.

The current chapter describes various TRAP methods to detect telomerase activity (TA) using gel-based methods, its advantages and deficits, how to perform an ELISA-based TRAP assay and how best to interpret its results. Since development of the TRAP assay in 1994, there have been numerous modifications and adaptations of the method from real-time PCR analysis, isothermal amplification and nanotechnology to CRISPR/Cas-based methods which will be briefly mentioned. However, it is not possible to cover all different TRAP methods and thus there is no comprehensiveness claimed by this chapter. Instead, the author describes various aspects of using TRAP assays including required controls, sample preparation, etc. in order to avoid pitfalls and set-backs in applying this rather complex and demanding technique. The TRAP assay is particularly important to support clinical diagnosis of cancer, analyze tumor therapy as well as to evaluate various approaches to inhibit TA as a form of anti-cancer therapy.

We conducted a systematic review and meta-analysis to assess the effects of lifestyle intervention on telomere length (TL).

Four databases were searched for studies reporting TL in leukocytes, before and after a lifestyle intervention. We computed random-effects meta-analysis on TL within intervention and control group after versus before intervention, and on changes in TL between groups. Sensitivity analyses and Meta-regression were conducted.

We included 20 studies in the systematic review (2995 participants, mean 50.3 years old, 77% women, 2045 following an intervention and 950 controls) and 19 in the meta-analysis. TL were similar at baseline between intervention and control groups. The physical activity ± diet group had an increase in TL (Effect size 0.17, 95%CI 0.03–0.31, p = 0.020) using changes within the intervention group, whereas TL shortened in the control group (−0.32, −0.61 to −0.02, p = 0.037). TL was longer in the physical activity ± diet intervention group (0.24, 0.08–0.40, p = 0.004) compared to controls after the intervention. Sensitivity analysis gave similar results. Meta-regressions demonstrated that combining strength and endurance exercise increased TL more than endurance alone or strength alone.

A lifestyle intervention with physical activity ± diet can increase telomere length, independently of population characteristics or baseline TL.

To systematically investigate the relationship between objective measures of physical capacity (e.g., cardio-respiratory fitness or daily step count) and biological age, measured in different ways.

PubMed; SCOPUS - Elsevier API; and Web of Science - ISI 1984-present, as well as contextual search engines used to identify additional relevant publications.

Cross-sectional and longitudinal studies that assessed the association between objectively measured physical capacity and biological aging in adult individuals (age>18).

Analysis of 28 studies demonstrated that physical capacity is positively associated with biological aging; the most dominant measures of physical capacity are muscular strength or gait speed. The majority of the studies estimated biological aging by a single methodology – either Leukocyte Telomere Length or DNA methylation levels.

This systematic review of the objective physical capacity measures used to estimate aging finds that the current literature is limited insofar as it overlooks the potential contribution of many feasible markers. We recommend measuring physical capacity in the context of aging using a wide range of modifiable behavioral markers, beyond simple muscle strength or simple gait speed. Forming a feasible and diversified method for estimating physical capacity through which it will also be possible to estimate biological aging in wide population studies is essential for the development of interventions that may alleviate the burden of age-related disease.

Telomeres are higher order structures that cap and protect chromosome ends. Telomeric DNA naturally shortens during somatic cell division and as a result of oxidative stress. Excessive shortening disrupts the integrity of the telomere, causing cellular senescence, one of the hallmarks of organismal ageing. The accumulation of senescent cells with ageing contributes to the loss of tissue homeostasis and the development of age-related pathologies. Hence, counteracting telomere shortening may be one relevant approach to develop strategies for healthier ageing. In this review I present the case for the existence of a link between oxidative stress, accelerated telomere shortening and cellular senescence. I also examine findings from human observational studies exploring associations between telomere length and oxidative stress-related parameters. Finally, I discuss results from randomised control trials testing the impact of non-pharmacological lifestyle interventions on the maintenance of telomere length, considering the potential mechanisms that might be involved.

Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are overrepresented in elderly patients. This provides specific challenges for the treatment, as the start of dialysis in vulnerable elderly patients may be associated with a rapid decline in functional performance. However, prognosis in elderly patients with ESRD is quite variable and related to the presence of comorbidity and geriatric impairments. The decision to start dialysis in elderly patients should always be based on shared decision making, which may be aided by the use of prediction models which should however not be used to withhold dialysis treatment. The treatment of ESRD in elderly patients should be based on a multidimensional treatment plan with a role for active rehabilitation.

Moreover, there also appears to be a reciprocal relationship between aging and CKD, as the presence of geriatric complications is also high in younger patients with ESRD. This has led to the hypothesis of a premature aging process associated with CKD, resulting in different phenotypes such as premature vascular aging, muscle wasting, bone disease, cognitive dysfunction and frailty. Prevention and treatment of this phenotype is based on optimal treatment of CKD, associated comorbidities, and lifestyle factors by established treatments. For the future, interventions, which are developed to combat the aging process in general, might also have relevance for the treatment of patients with CKD, but their role should always be investigated in adequately powered clinical trials, as results obtained in experimental trials may not be directly translatable to the clinical situation of elderly patients. In the meantime, physical exercise is a very important intervention, by improving both physical capacity and functional performance, as well as by a direct effect on the aging process.