Adversity in early life – whether preterm birth or socioeconomic disadvantage in childhood – accelerates aging, according to two recent studies, but underlying mechanisms remain unclear, and methods of investigation continue to evolve.
While one study used an established epigenetic clock to measure biological age among adults with extremely low birth weight, the other showcased a relatively new tool to measure pace of biological aging in disadvantaged children, suggesting that the metric may one day serve as a real-time measure of interventional efficacy.
These findings build upon previous studies that have demonstrated a correlation between biological age, also known as methylation age, and an increased risk of health problems later in life, according to Daniel A. Notterman, MD, professor of molecular biology at Princeton (N.J.) University.
“Finding that a person’s methylation age is greater than their chronological age has been taken as evidence of increased ‘biological age’ and perhaps a tendency to greater future morbidity,” Dr. Notterman wrote in a Pediatrics editorial. “Indeed, methylation age is advanced in association with a number of childhood and midlife adversities as well as morbidities such as atherosclerosis, cancer, and obesity.”
Extremely low birth weight associated with faster aging in men
For some individuals, accelerated biological aging begins at birth, or even in utero, according to Ryan J. Van Lieshout, MD, PhD, Canada Research Chair in the Perinatal Programming of Mental Disorders and the Albert Einstein/Irving Zucker Chair in Neuroscience at McMaster University, Hamilton, Ont., and colleagues.
The investigators conducted a study involving 45 extremely low birth weight (ELBW) survivors and 49 individuals born at normal birth weight. All participants were drawn from a longitudinal study conducted between 1977 and 1982 that assessed advances in neonatal intensive care. Controls were recruited at 8 years of age and matched with ELBW survivors based on family socioeconomic status, sex, and age. Follow-up continued through adulthood, allowing for the present trial to compare data from ages 8, 30, and 35.
Using samples of buccal epithelial cells, the investigators measured biological age with the Horvath epigenetic clock, the most commonly used tool of its kind, which measures cytosine-5 methylation at 353 cytosine-phosphate-guanine sites. Results were adjusted for a variety of covariates, such as smoking status, body mass index, number of chronic health conditions, and others.
Between groups, ELBW survivors trended toward older biological age, compared with adults born at normal birth weight (29.0 vs. 27.9 years), a difference that was not statistically significant. Further analysis, however, showed a significant sex-based difference between groups: Male survivors of ELBW, in adulthood, were almost 5 years biologically older than men born at normal birth weight (31.4 vs. 26.9 years; P = .01).
“[W]e provide preliminary evidence of a new link between ELBW and accelerated biological aging among men,” the investigators concluded.
In an accompanying editorial, Pam Factor-Litvak, PhD, vice chair of epidemiology at Columbia University, New York, wrote, “The findings are intriguing and open many questions for further study.”
Dr. Factor-Litvak noted that it remains unclear whether differences in biological aging were present at birth.
“[D]ifferences would provide evidence that accelerated aging begins during the in utero period, perhaps because of maternal undernutrition, stress, or another exposure,” Dr. Factor-Litvak wrote. “[R]eductions in chronic stress levels, which may begin for neonates with ELBW in utero and in the first hours of life, may provide an opportunity for interventions,” she added.
According to Calvin J. Hobel, MD, professor of pediatrics at Cedars-Sinai and professor of obstetrics and gynecology at University of California, Los Angeles, who has been studying preterm birth for more than 40 years, interventions may need to begin even earlier.
Dr. Calvin J. Hobel
“The only way to prevent preterm birth is to do it before women get pregnant,” Dr. Hobel said in an interview. “The reason for preterm birth and poor fetal growth is the fact that the mother has early cardiovascular disease – unrecognized.”
Compared with women who give birth to full-term infants, women who give birth to preterm infants typically have increased blood pressure, Dr. Hobel said. Although these elevations in blood pressure are generally asymptomatic and not high enough to be classified as hypertensive, they impact umbilical artery vascular resistance starting at 28 weeks of gestation.
“In utero, [preterm infants] are programmed for increased vascular resistance and increased risk of cardiovascular disease,” Dr. Hobel said.
Regarding the effects of ELBW in men versus women, Dr. Hobel suggested that dissimilar neuroendocrine systems between sexes may protect females from adverse outcomes, although exact mechanisms remain elusive.