Medical Bulletin 21/October/2025

Metabolic syndrome is a cluster of conditions including high blood pressure, high blood sugar, excess abdominal fat, and abnormal cholesterol or triglyceride levels that increase the risk of heart disease, stroke, and diabetes. The team reviewed multiple global studies to assess the association between this syndrome and the incidence of five major gynaecological cancers: ovarian, endometrial, cervical, vaginal, and vulvar cancer.

Lead author Dr Susan Idicula-Thomas from NIRRCH explained, “The pathophysiology from the research papers reviewed established a clear link.” The data showed that women with metabolic syndrome had a 26% higher risk of cervical cancer and a 45% higher risk of endometrial cancer over time, compared to those without the syndrome. Co-author Denny John from MS Ramaiah University, Bengaluru, added that women with metabolic syndrome have "three times the odds of developing ovarian cancer compared to those who do not have it."

While the study is based on a global review and couldn’t include any Indian studies due to limitations in inclusion criteria and data quality, the authors emphasized the high prevalence of metabolic syndrome in India affecting nearly 30% of the population, with higher rates in women (35%) than in men (26%).

“Metabolic syndrome is an epidemic in both urban and rural populations. The cancer rate is also increasing,” Dr Idicula-Thomas noted. “If these conditions are linked as our review has shown, the fact that metabolic syndrome is preventable in many cases means primary prevention will help prevent both.”

Reference: Kundu I, John D, Ansari I, Pavithran K, Idicula-Thomas S. Risk of gynaecologic cancers in women with metabolic syndrome: A systematic review & meta-analysis. Indian J Med Res. 2025 Aug;162:197-210.

Why Women Face Higher Risk of Alzheimer’s and Multiple Sclerosis

A recent study published in Science Translational Medicine, has identified a gene on the X chromosome that drives inflammation in the female brain potentially explaining why women are disproportionately affected by neurological conditions such as Alzheimer’s disease and multiple sclerosis (MS).

Researchers from UCLA Health Sciences used a mouse model of multiple sclerosis to study a gene called Kdm6a, located on the X chromosome. Females, who carry two X chromosomes compared to one in males, receive a “double dose” of the gene’s inflammatory effect in brain immune cells known as microglia. This heightened inflammation is known to contribute to aging, Alzheimer’s disease, and MS.

First author Dr. Yuichiro Itoh of the Voskuhl Lab deactivated Kdm6a in microglia cells. This genetic "knockout" caused the inflammatory molecules to shift into a resting state, significantly improving MS-like symptoms in female mice. The team also tested a pharmacological “knockdown” using metformin, a diabetes drug under investigation for anti-aging properties. Again, the treatment significantly reduced inflammation in females but had little effect on males.

“This is consistent with there being 'more to block' in females due to having two copies of the X-linked gene,” said Dr. Rhonda Voskuhl, lead author and director of the Multiple Sclerosis Program at UCLA Health, noting that these differences could impact how women respond to treatments like metformin.

The study also offers a compelling explanation for brain fog in menopausal women, linking the loss of estrogen, an anti-inflammatory hormone, to increased activity of the proinflammatory X-linked gene. According to Voskuhl, targeting brain-specific estrogens may help restore the balance and protect women’s brains during aging.

Reference: Itoh, Y., et al. (2025). Deletion of the X-chromosomal gene Kdm6a in microglia of female mice ameliorates neuroinflammation and restores translatome profiles. Science Translational Medicine. doi.org/10.1126/scitranslmed.adq3401

Long-term Exercise Keeps Immune System Younger and Sharper: Study Finds

A new study published in Scientific Reports reveals that long-term endurance training not only benefits cardiovascular health and muscle strength but also significantly enhances immune function in older adults. The study found that older individuals with a long history of endurance exercise had more adaptable and metabolically efficient immune cells, specifically natural killer (NK) cells, compared to their sedentary peers.

NK cells are a type of white blood cell essential for early immune defense, responsible for eliminating infected and abnormal cells. The researchers studied nine participants with an average age of 64, divided into trained and untrained groups. Those with over 20 years of endurance training showed NK cells that were less inflammatory, more energy-efficient, and more resilient to immune challenges.

To understand how exercise impacts immune function, the team also tested NK cell responses to inflammatory triggers and pharmacological agents such as propranolol and rapamycin. Despite the inhibition of key immune signaling pathways, NK cells from trained individuals maintained function, while those from untrained individuals showed cellular exhaustion.

"Decades of physical activity seem to 'train' the immune system to avoid exaggerated inflammatory responses," said Dr. Luciele Minuzzi of Justus Liebig University Giessen. These findings support the role of exercise in healthy aging, offering critical insight into preventing inflammation-related diseases through long-term physical activity.

Reference: Luciele Guerra Minuzzi, Helena Batatinha, Christopher Weyh, Vidya Srokshna Balasubramanian Lakshmi, Carmen Fiuza-Luces, Beatriz G. Gálvez, Alejandro Lucia, Ana Maria Teixeira, Natascha Sommer, José Cesar Rosa-Neto, Fabio Santos Lira, Karsten Krüger. Natural killer cells from endurance-trained older adults show improved functional and metabolic responses to adrenergic blockade and mTOR inhibition. Scientific Reports, 2025; 15 (1) DOI: 10.1038/s41598-025-06057-y