People age at a similar chronological rate, but differ in their physical and cognitive rates of aging. The decline in functional capacity that can be separated from chronological age is known as biological age, and is influenced by the interaction of our genes and environment.
What’s responsible for these divergent aging trajectories? One theory, known as the epigenetic theory of aging, posits that aging is an unintended consequence of our biological development and maintenance programs, which give rise to distinct cellular changes or “molecular footprints.”[1] One of the most prominent age-related processes is known as DNA methylation (DNAm). DNAm involves the addition of a methyl (CH3) group to DNA at a location called a CpG site. DNAm causes changes in gene transcription and gene expression.
“Biological clocks” (also known as epigenetic clocks) precisely measure the levels of DNAm across various cells, tissues, and organs. Because they have been trained and tested on large datasets, biological clocks can not only accurately predict chronological age, but also biological age and other outcomes of interest, including the risk for age-related diseases, cancer, and all-cause mortality.[2][3][4] In many instances, epigenetic age predicts morbidity and mortality outcomes better than chronological age or traditional risk factors.
Perhaps the biggest value of biological clocks is not in their ability to correctly predict someone’s chronological age, but in what they can inform us about healthy biological aging. The discrepancy between a person’s biological age, as measured using epigenetic clocks, and their chronological age captures whether they’re aging faster or slower than normal. This is known as “age acceleration.” Someone with an epigenetic age older than their chronological age is said to have a positive age acceleration, while someone whose epigenetic age is younger than their chronological age has a negative age acceleration; the latter is desirable.
Epigenetic age and age acceleration can help predict a person’s lifetime health risks, such as their risk of developing certain cancers or their probability of becoming a centenarian (i.e., living to be 100 years old). Relatedly, certain diseases are associated with increased epigenetic age and positive age acceleration, like Down syndrome and Parkinson’s disease.[1] Furthermore, biological clocks are sensitive to lifestyle interventions. For example, the intake of fish, fruit, and vegetables is associated with negative age acceleration, while high levels of inflammation, blood glucose, blood pressure, and obesity are linked to positive age acceleration.[5] This makes biological clocks attractive tools for assessing the effects of healthy lifestyle interventions in randomized controlled trials.
While numerous clocks have been developed, some of the major commonly used ones include the Horvath age acceleration clock, the Hannum age acceleration clock, Levine’s “PhenoAge” clock, Lu’s “GrimAge” clock, Weidner’s age clock, and Zhang’s mortality clock.[5]
While the area of biological clocks is not without controversy, the field is rapidly evolving. Soon enough, you may be celebrating your biological age on your birthday.
References
- ^Steve Horvath, Kenneth RajDNA methylation-based biomarkers and the epigenetic clock theory of ageingNat Rev Genet.(2018 Jun)
- ^Morgan E Levine, Ake T Lu, Austin Quach, Brian H Chen, Themistocles L Assimes, Stefania Bandinelli, Lifang Hou, Andrea A Baccarelli, James D Stewart, Yun Li, Eric A Whitsel, James G Wilson, Alex P Reiner, Abraham Aviv, Kurt Lohman, Yongmei Liu, Luigi Ferrucci, Steve HorvathAn epigenetic biomarker of aging for lifespan and healthspanAging (Albany NY).(2018 Apr 18)
- ^Zheng Y, Joyce BT, Colicino E, Liu L, Zhang W, Dai Q, Shrubsole MJ, Kibbe WA, Gao T, Zhang Z, Jafari N, Vokonas P, Schwartz J, Baccarelli AA, Hou LBlood Epigenetic Age may Predict Cancer Incidence and Mortality.EBioMedicine.(2016-Mar)
- ^Brian H Chen, Riccardo E Marioni, Elena Colicino, Marjolein J Peters, Cavin K Ward-Caviness, Pei-Chien Tsai, Nicholas S Roetker, Allan C Just, Ellen W Demerath, Weihua Guan, Jan Bressler, Myriam Fornage, Stephanie Studenski, Amy R Vandiver, Ann Zenobia Moore, Toshiko Tanaka, Douglas P Kiel, Liming Liang, Pantel Vokonas, Joel Schwartz, Kathryn L Lunetta, Joanne M Murabito, Stefania Bandinelli, Dena G Hernandez, David Melzer, Michael Nalls, Luke C Pilling, Timothy R Price, Andrew B Singleton, Christian Gieger, Rolf Holle, Anja Kretschmer, Florian Kronenberg, Sonja Kunze, Jakob Linseisen, Christine Meisinger, Wolfgang Rathmann, Melanie Waldenberger, Peter M Visscher, Sonia Shah, Naomi R Wray, Allan F McRae, Oscar H Franco, Albert Hofman, André G Uitterlinden, Devin Absher, Themistocles Assimes, Morgan E Levine, Ake T Lu, Philip S Tsao, Lifang Hou, JoAnn E Manson, Cara L Carty, Andrea Z LaCroix, Alexander P Reiner, Tim D Spector, Andrew P Feinberg, Daniel Levy, Andrea Baccarelli, Joyce vaDNA methylation-based measures of biological age: meta-analysis predicting time to deathAging (Albany NY).(2016 Sep 28)
- ^Ryan CP"Epigenetic clocks": Theory and applications in human biology.Am J Hum Biol.(2021-May)