Editor-in-Chief︱Sizhen Wang
Singapore-led
collaboration develops novel method to accurately measure key marker of
biological ageingA
new approach that ‘baits’ the caps or telomeres protecting the ends of
chromosomes could provide information on how rapidly we are ageing and what we
need to do to slow it down.SINGAPORE,
16 February 2023 – Telomeres—the caps at the ends of chromosomes that protect
our genetic materials from the brunt of cellular wear and tear—are known to
shorten and fray over time. Lifestyle, diet and stress can exacerbate this
process, leading to early loss of telomere protection and increasing the
chances of early ageing and lifestyle diseases, such as cancer and heart
diseases.To
date, approaches for measuring biological ageing based on telomere length have
been limited as they can only ascertain average telomere lengths within a pool
of DNA fragments, or are time-consuming and require highly-skilled specialists.
Being able to accurately and efficiently measure the length of an individual’s
telomeres could open the doors to developing lifestyle interventions that slow
ageing and prevent disease.Publishing
in the journal Nature Communications, scientists at Duke-NUS Medical School, National
Heart Centre Singapore (NHCS) and colleagues in Singapore, China and the USA
have recently devised a way to rapidly and precisely measure the length of a
single telomere.Associate
Professor Li Shang, senior author of the study from Duke-NUS Cancer & Stem
Cell Biology Programme, explained, “We applied a novel approach that uses DNA
sequences—we call them ‘telobaits’—to latch onto the ends of telomeres in large
pools of DNA fragments, like fishing in pond. Then, with specific scissor-like
enzymes, we snip the telomeres out of the pools.“Using
high-throughput genetic sequencing technology, we were able to read the DNA
‘letters’ that comprised each individual telomere, allowing us to very
precisely measure their lengths.”The
team successfully validated this approach when they tested it using human cell
lines and patient cells. Interestingly, the sequencing results revealed that
the genetic sequences within certain parts of the telomeres, known as telomeric
variant sequences, were distinct to each individual person.“Based
on this insight, a future area of study for us is the possible use of telomeric
variant sequences as a means of biological identification, which could
potentially prove useful for expanding the field of forensic science,” said
Assoc Prof Li. The team believes this new approach could be used as a
predictive biomarker for human ageing and disease at the individual level, as
well as for population-level studies on the impacts of lifestyle, diet and the
environment on human health.Senior
co-author of the study, Assoc Prof Angela Koh, who is Senior Consultant with
the Department of Cardiology at NHCS and Associate Professor with the
SingHealth Duke-NUSCardiovascular Sciences Academic Clinical Programme,
remarked, “This method for telomere length measurement is an important advance
in the field of ageing research. From the clinical perspective, we view this as
a very promising method for understanding clinical diseases associated with
ageing such as cardiovascular disease. Our partnership signifies what can be achieved
by clinician-and-biomedical scientists to bring complex lab methods towards
simpler, quantifiable methods that may be used in broader clinical labs in the
future.”The
study was a collaboration led by Duke-NUS and NHCS with partners in Singapore,
namely the Cancer Science Institute of Singapore and Yong Loo Lin School of
Medicine, National University of Singapore; A*STAR’s Genome Institute of
Singapore and Institute of Molecular and Cell Biology; National Cancer Centre
Singapore; Singapore General Hospital; and the SingHealth Duke-NUS Institute of
Precision Medicine; as well as Kumamoto University (Japan), Guangzhou Medical
University (China), The Chinese University of Hong Kong-Shenzhen (China),
Shanghai University (China), and the University of California, Davis (USA).Reference:Tham, CY., Poon, L., Yan, T. et al. High-throughput telomere length measurement
at nucleotide resolution using the PacBio high fidelity sequencing platform.Nat Commun 14, 281 (2023). https://doi.org/10.1038/s41467-023-35823-7About
Duke-NUS Medical SchoolDuke-NUS
is Singapore’s flagship graduate entry medical school, established in 2005 with
a strategic, government-led partnership between two world-class institutions:
Duke University School of Medicine and the National University of Singapore
(NUS). Through an innovative curriculum, students at Duke-NUS are nurtured to
become multi-faceted ‘Clinicians Plus’ poised to steer the healthcare and
biomedical ecosystem in Singapore and beyond. A leader in ground-breaking
research and translational innovation, Duke-NUS has gained international renown
through its five signature research programmes and 10 centres. The enduring
impact of its discoveries is amplified by its successful Academic Medicine
partnership with Singapore Health Services (SingHealth), Singapore’s largest
healthcare group. This strategic alliance has spawned 15 Academic Clinical
Programmes, which harness multi-disciplinary research and education to transform
medicine and improve lives.
For
more information, please visit www.duke-nus.edu.sgAbout
National Heart Centre SingaporeThe
National Heart Centre Singapore (NHCS) is a 185-bed national and regional
referral centre for cardiovascular diseases. NHCS provides a one-stop comprehensive
cardiac care ranging from preventive, diagnostic, therapeutic to rehabilitative
services. It is also the only heart and lung transplantation centre in
Singapore.
Each
year, NHCS handles over 120,000 outpatient consultations, 9,000 interventional andsurgical
procedures and 10,000 inpatients. Its clinical outcomes for heart attack
treatment, balloon
angioplasty with stenting and coronary bypass surgery have been shown to be equivalent
to international benchmarks.Established
in 1998, NHCS is the pioneer in cardiovascular care in Singapore.For
more information, please visit www.nhcs.com.sg.
作者：李赏
（照片提供自：李赏课题组）
作者简介（上下滑动阅读）李赏教授, 杜克—国大医学研究生院肿瘤和干细胞系副教授. 李赏教授在北京医科大学(现为北京大学医学院)获得医学学士学位. 他在德克萨斯州大学圣安东尼奥分校李文华教授(台湾科学院院士)实验室获得分子医学博士学位. 他随后在加州大学旧金山分校伊丽莎白.布莱克本实验室做博士后研究. 伊丽莎白.布莱克本是2009年诺贝尓生理和医学奖获得者. 李赏教授在2010年加入杜克—国大医学研究生院. 他的室验室主要研究端粒酶在人类肿瘤细胞和干细胞的调控, 以及发展新的计术来应用于抗肿瘤和抗衰老的治疗. 李赏教授也是CRISPR中心主任. 该中心为杜克—国大医学研究生院和国立肿瘤中心提供服务. 李赏教授已发表超过50篇论文和文章, 包括: Nature, Science, Cell, Molecular Cell, Nature Cell Biology, Cancer Discovery, Nature Comm. 等期刊 (h-index=28, i10-index=38)
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