Aging and age-related diseases are influenced by reproductive timing. A new study published at eLife reveals that girls who undergo puberty (start menstruation) before 11 or women who give birth before 21 have double the risk of developing type 2 diabetes, heart failure, obesity, and a quadruple risk of severe metabolic disorders.
eLifeThe study also shows that delayed puberty and childbirth are genetically linked to longer lifespan, lower frailty, slower epigenetic aging, and reduced risks of age-related diseases like type 2 diabetes and Alzheimer's disease.
"This research underscores the importance for healthcare providers to consider a woman's menstrual and reproductive history beyond OB/GYN care," says Buck professor Pankaj Kapahi, Ph.D., senior author of the study. "These factors can significantly influence various age-related diseases and should factor into overall health assessments."
The research is based on analyzing nearly 200,000 women from UK Biobank to confirm genetic associations.
"We discovered 126 genetic markers impacting how early puberty and childbirth affect aging," stated postdoctoral fellow Yifan Xiang, MD. "Many of these are related to well-known longevity pathways such as IGF-1, growth hormone, AMPK, and mTOR signaling."
Evolution's natural selection often emphasizes traits beneficial for early reproduction but may have negative effects later in life, according to the antagonistic pleiotropy theory of aging.
Kapahi notes: "Our findings provide substantial human evidence supporting this theory. We show genetic factors favoring early reproduction carry costs like accelerated aging and disease."
The research emphasizes that Body Mass Index (BMI) is crucial in influencing metabolic diseases related to reproductive events.
"Better nutrient absorption benefits offspring but can increase obesity and diabetes risks with abundant nutrients," Kapahi states. "Understanding these long-term impacts can help develop personalized health strategies, including lifestyle modifications, metabolic screenings, and tailored dietary recommendations."
Kapahi highlights that taking into account reproductive timing is particularly relevant today as research shows US girls are starting puberty about three months earlier per decade since the 1970s, potentially due to obesity.
He also mentions that current research guidelines suggest using both sexes in preclinical research but recognizes there's still a need to address traditional models relying on virgin female mice, which might not accurately reflect human aging scenarios.
"If early reproduction is shaped by evolution at the cost of aging, how can we use this knowledge to extend healthspan?" Kapahi asks. "Understanding these genetic tradeoffs empowers us to make educated choices about health."
The study also identifies several genetic pathways that could be targeted for optimizing health of both mothers and offspring.
Other Buck researchers involved include: Vineeta Tanwar, Parminder Singh, and Lizellen LaFollette.