Telomere length analysis from minimally‐invasively collected samples: Methods development and meta‐analysis of the validity of different sampling techniques

Abstract

Objectives Telomeres are the protective caps of chromosomes. They shorten with cell replication, age, and possibly environmental stimuli (eg, infection and stress). Short telomere length (TL) predicts subsequent worse health. Although venous whole blood (VWB) is most commonly used for TL measurement, other, more minimally invasive, sampling techniques are becoming increasingly common due to their field‐friendliness, allowing for feasible measurement in low‐resource contexts. We conducted statistical validation work for measuring TL in dried blood spots (DBS) and incorporated our results into a meta‐analysis evaluating minimally invasive sampling techniques to measure TL. Methods We isolated DNA extracts from DBS using a modified extraction protocol and tested how they endured different shipping conditions and long‐term cryostorage. We then included our in‐house DBS TL validation statistics (correlation values with VWB TL and age) in a series of meta‐analyses of results from 24 other studies that published similar associations for values between TL measured in DBS, saliva, and buccal cells. Results Our modified DBS extraction technique produced DNA yields that were roughly twice as large as previously recorded. Partially extracted DBS DNA was stable for 7 days at room temperature, and still provided reliable TL measurements, as determined by external validation statistics. In our meta‐analysis, DBS TL had the highest external validity, followed by saliva, and then buccal cells—possibly reflecting similarities/differences in cellular composition vs VWB. Conclusions DBS DNA is the best proxy for VWB from the three minimally‐invasively specimen types evaluated and can be used to expand TL research to diverse settings and populations.

Applying minimally invasive biomarkers of chronic stress across complex ecological contexts

“…Some researchers have described evidence of stress‐related acceleration in processes associated with aging at the chromosomal and epigenetic level. For example, methods are now available for reliable extraction from DBS of DNA suitable for measuring telomere length (Rej et al, 2021 ). Telomeres shorten with age, leading to elevated risk of poor health, but there also is evidence that they shorten more rapidly in light of chronic stress; for example, among African American adults in Florida experiencing greater racial discrimination (Rej et al, 2020 ).…”

“…Exploring all possible methods and their contingencies is far beyond the scope of any single article, although excellent resources are available (e.g., Brewis et al, 2021 ; Ice & James, 2007 ). Some promising new methods are included here only by brief reference, such as the conserved transcriptional response to adversity (Cole, 2019 ; Snodgrass et al, 2018 ), telomere length (Rej et al, 2021 ; Rej et al, 2020 ), and epigenetic aging (Gettler et al, 2020 ; Palma‐Gudiel et al, 2020 ). Our focus will be on a subset of methods that are (1) currently accessible to the broadest possible range of human biologists working in a variety of field contexts; (2) minimally invasive; and (3) sufficiently well‐established to provide for a discussion of strengths, weaknesses, and ecological contingencies when working across diverse human populations.…”

Coming up short: Comparing venous blood, dried blood spots & saliva samples for measuring telomere length in health equity research

“…This can pose a major logistical problem for observational studies of population health and aging inequity, which require diverse samples that include the most marginalized members of society [21]. Increasingly, investigators examining TL in large, population-based studies have turned to measurement of telomere length in DNA derived from saliva or buccal swabs [22][23][24][25][26] and some researchers have begun to include telomere data drawn from finger-prick dried blood spots (DBS) [27][28][29]. These approaches are seen as minimally invasive, scalable, and less expensive alternatives to venous blood that could be used widely in social epidemiologic and population health studies, including in hard-to-reach populations.…”

Current and future applications of biomarkers in samples collected through minimally invasive methods for cancer medicine and population‐based research

“…Furthermore, the impact of infectious processes on the false-positive rates of many cancer biomarker diagnostics can be investigated by measuring these biomarkers in minimally invasively collected sample types. Validated venous blood biomarkers can also potentially be adapted for use in minimally invasively collected sample types like DBS, which has been extensively used with immune, hormonal, and other biomarkers of physiology and health (Eick et al, 2016(Eick et al, , 2017(Eick et al, , 2019(Eick et al, , 2020McDade et al, 2007McDade et al, , 2012McDade & Shell-Duncan, 2002;Rej et al, 2021). However, more basic research is needed to develop cancer biomarkers that can be measured in minimally invasively collected sample types and to ascertain which technological platform can be used for optimal quantitation and cost-effectiveness.…”

“…Medical research has thoroughly examined many molecules that are suitable for the detection of cancer at a population level, despite presently being of limited use in clinical settings due to more stringent requirements for sensitivity and specificity. Uniting oncology with human biology, which is a leader in the development of minimally invasive techniques for population-based studies (Eick et al, 2016(Eick et al, , 2017(Eick et al, , 2019(Eick et al, , 2020Gildner, 2021;McDade, 2014;McDade et al, 2007McDade et al, , 2020Rej et al, 2021;Valeggia, 2007), provides an opportunity to apply well-researched methods to a field that has recognized the need for greater biomarker sampling and less invasive techniques.…”