Lifeboat Foundation

By Sher Bahadur Poudel & Shoshana Yakar et al.

Several mouse lines with congenital growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis disruption have shown improved health and extended lifespan. The current study investigated how inactivating this axis, specifically during aging, impacts the healthspan. We used a tamoxifen-inducible global GH receptor (GHR) knockout mouse model starting at 12 months and followed the mice until 24 months of age (iGHRKO_12–24 mice). We found sex-and tissue-specific effects, with some being pro-aging and others anti-aging. Measuring an array of cytokines in serum revealed that inactivation of the GH/IGF-1 axis at 12 months did not affect systemic inflammation during aging. On the other hand, hypothalamic inflammation was significantly reduced in iGHRKO_12–24 mice, evidenced by GFAP⁺ (glial fibrillary acidic protein, a marker of astrocytes) and Iba-1⁺ (a marker for microglia). Liver RNAseq analysis indicated feminization of the male transcriptome, with significant changes in the expression of monooxygenase, sulfotransferase, and solute-carrier-transporter gene clusters. Finally, we found impaired bone morphology, more pronounced in male iGHRKO_12–24 mice and correlated with GH/IGF-1 inactivation onset age. We conclude that inhibiting the GH/IGF-1 axis during aging only partially preserves the beneficial healthspan effects observed with congenital GH deficiency.

Inactivating the GH axis during aging has sex-and tissue-specific effects on healthspan. Deleting the GH receptor (GHR) in the entire body at 12 months of age led to feminizing the male liver transcriptome, significantly altering the expression of p450 and sulfotransferase gene clusters. While GHR deletion during aging did not impact systemic inflammation, it was linked to reduced hypothalamic inflammation. Additionally, we observed impaired bone morphology, particularly in male mice, which correlated with the age at which GH/IGF-1 inactivation began. Our findings suggest that inhibiting the GH axis during aging only partially maintains the beneficial healthspan effects seen with congenital GH deficiency.

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Inhibiting TLR7, an immune signaling protein, may help preserve the protective layer surrounding nerve fibers in the brain during both Alzheimer’s disease and ordinary aging, suggests a study led by researchers at Weill Cornell Medicine. The research is published in the journal Science.

Most nerve fibers in vertebrates are encased in sheaths made largely of myelin, a protein that protects the fibers and greatly enhances the efficiency of their signal conduction. The destruction of myelin sheaths—demyelination—can occur in the context of brain inflammation and can lead to cognitive, movement and other neurological problems. The phenomenon is seen in multiple sclerosis (MS), Alzheimer’s, Parkinson’s and other neurological conditions, as well as in ordinary aging.

Demyelination-linked disorders often show sex differences, and in the study, the researchers looked for underlying mechanisms of demyelination that might help explain these differences. Their experiments in mouse models of Alzheimer’s uncovered TLR7 as a driver of inflammatory demyelination especially in males, but also showed that removing or inhibiting this immune protein can protect against demyelination in both males and females.

We further investigated whether these associations were driven by caffeine by performing two meta-analyses on the PREDICT1 and PREDICT3 22UKA samples for which the intake of decaffeinated and caffeinated coffee was available. Partial correlations between SGB-ranked abundances and decaffeinated versus caffeinated coffee were run independently (excluding individuals who drank exclusively caffeinated or decaffeinated coffee, respectively). In addition, partial correlations were also adjusted for the other type of coffee consumed by the individuals in case their record reported both kinds. We identified 150 correlations, which remained highly significant after controlling for the decaffeinated coffee intake (q 0.001, n_participants = 12,089; Extended Data Fig. 4c and Supplementary Table 8). This indicated a substantial independence on caffeine of the observed impact on the microbiome. Next, we analysed the decaffeinated coffee association with the microbiome in individuals consuming decaffeinated coffee and adjusting by caffeinated coffee as well as by sex, age and BMI. In this reduced set of samples (n_participants = 6,089) we identified 22 correlations at q 0.001 and 66 at q 0.1 (Supplementary Table 9). The top three correlations identified were L. asaccharolyticus (ρ = 0.27 (0.21–0.33), q 10⁻¹⁰), the Lachnospiraceae SGB4777 (ρ = 0.18 (0.16–0.21), q 10⁻¹⁰), and M. coli (SGB29305, ρ = 0.17 (0.13–0.2), q 10⁻¹⁰; Fig. 2b).

As expected, several coffee-associated SGBs were also L. asaccharolyticus co-abundant SGBs, possibly indicating similar independent stimulatory effects of coffee rather than ecological relations (Extended Data Fig. 5 and Supplementary Table 10). The top-five SGBs associated with L. asaccharolyticus abundance were, however, not among the strongest associations with coffee. In particular, the two SGBs with the strongest co-abundance pattern with L. asaccharolyticus were Dysosmobacter welbionis (SGB15078) and the Clostridiales bacterium SGB15143 (ρ = 0.57 and 0.51, respectively, q 1 × 10⁻¹⁰; Extended Data Fig. 5), which were both only weakly associated with total coffee (ρ ≤ 0.05; Supplementary Table 7). Overall, these results indicate that a panel of species, and in particular L. asaccharolyticus is robustly associated with total and decaffeinated coffee consumption, suggesting that the association is not purely due to caffeine.

Among the top coffee-associated SGBs, L. asaccharolyticus showed the highest and the most uniform prevalence across all the cohorts (93.5%; Fig. 2c). In the ‘never’ group from the USA, its prevalence was uniformly high (average prevalence of 87.8 ± 2%) across nine different regions (samples from PREDICT2 and PREDICT3 US22A, n = 9,210). Over and above this, however, it was uniformly increased in all regions when considering coffee consumption; it increased from 87.8% to 95.6% in moderate drinkers and from 95.6% to 97.7% in high drinkers (Fig. 2d and Supplementary Table 11). Degree of urbanization (rural versus urban living context) was not associated with L. asaccharolyticus in the microbiome (Extended Data Fig. 6 and Supplementary Table 12). Overall, the median abundance of L. asaccharolyticus ranged from 4.5-to 8-fold higher in the high compared with the never group (in the PREDICT3 US22A and MBS–MLVS cohorts), and 3.4-to 6.4-fold higher in the moderate versus the never group (in the PREDICT2 and MBS–MLVS cohorts; Supplementary Table 13). By contrast, the highest median fold change between moderate and high drinkers was only 1.4 and did not reach statistical significance in three out of five cohorts (Fig. 3a and Supplementary Table 14).

This age-related deterioration affects both innate and adaptive immunity, compromising immune function and leading to chronic inflammation that accelerates aging. Immunosenescence is characterized by alterations in immune cell populations and impaired functionality, resulting in increased susceptibility to infections, diminished vaccine efficacy, and higher prevalence of age-related diseases. Chronic low-grade inflammation further exacerbates these issues, contributing to a decline in overall health and resilience. This review delves into the characteristics of immunosenescence and examines the various intrinsic and extrinsic factors contributing to immune aging and how the hallmarks of aging and cell fates can play a crucial role in this process. Additionally, it discusses the impact of sex, age, social determinants, and gut microbiota health on immune aging, illustrating the complex interplay of these factors in altering immune function. Furthermore, the concept of immune resilience is explored, focusing on the metrics for assessing immune health and identifying strategies to enhance immune function. These strategies include lifestyle interventions such as diet, regular physical activity, stress management, and the use of gerotherapeutics and other approaches. Understanding and mitigating the effects of immunosenescence are crucial for developing interventions that support robust immune responses in aged individuals.

The immune system plays a crucial role in protecting our bodies from harmful pathogens. It is divided into two segments: innate immunity and adaptive immunity. The innate immune system acts as an immediate but non-specific first responder to defend against pathogens, composed of phagocytic and natural killer cells. Besides innate immune cells, another important component of the innate system includes physical barriers like skin and mucous membranes. Meanwhile, adaptive immunity is more specialized and requires time to mount a high-affinity and specific response, relying on anticipatory receptors that recognize pathogen-specific antigens. The adaptive immune response is centered around B and T lymphocytes, which are produced in the bone marrow and thymus, respectively (Farber, 2020; Lam et al., 2024). With age, the ability of our immune system to mount productive and timely responses to pathogens diminishes.

A study found that male worms’ brains can activate conflicting memories, but behavior is driven by the more beneficial one. This research sheds light on how brains prioritize information, offering insights into conditions like PTSD.

A new study by UCL researchers reveals that two conflicting memories can simultaneously be activated in a worm’s brain, even though only one memory directly influences the animal’s behavior.

In the paper published in Current Biology, the researchers showed how an animal’s sex drive can at times outweigh the need to eat when determining behavior, as they investigated what happens when a worm smells an odor that has been linked to both good experiences (mating) and bad experiences (starvation).

A series of studies on humans and mice examined sex differences in reactions to anesthetics, revealing that female brains are more resistant to the hypnotic effects of these drugs. Testosterone administration increased sensitivity to anesthetics in mice, while castration enhanced anesthetic resistance. In humans, females regained consciousness and recovered cognitive function faster than males after identical exposure to anesthetics. The study was published in Neuroscience.

General anesthetics are drugs that induce a reversible loss of consciousness, primarily used during surgical procedures to block pain and prevent awareness. They are essential in medicine because they enable complex surgeries that would otherwise be intolerable due to pain, allowing patients to undergo invasive procedures safely and comfortably.

The history of general anesthesia dates back to the 19th century, with the first successful public demonstration by Dr. William Morton in 1846. Before anesthetics, surgery was excruciating and dangerous, often performed only in dire cases due to the severe pain and risks. Over time, safer and more effective agents, such as chloroform and eventually modern inhaled and intravenous anesthetics, were developed. Today, general anesthesia is administered by specialized professionals called anesthesiologists, who monitor and adjust the dosage to ensure patient safety.

Male and female mice use different brain circuits to process threats, revealing sex-specific neural pathways despite similar behaviors. These findings suggest the need for sex-inclusive neuroscience research to improve understanding and treatments.

With their slender tails, human sperm propel themselves through viscous fluids, seemingly in defiance of Newton’s third law of motion, according to a recent study that characterizes the motion of these sex cells and single-celled algae.

Kenta Ishimoto, a mathematical scientist at Kyoto University, and colleagues investigated these non-reciprocal interactions in sperm and other microscopic biological swimmers, to figure out how they slither through substances that should, in theory, resist their movement.

When Newton conceived his now-famed laws of motion in 1686, he sought to explain the relationship between a physical object and the forces acting upon it with a few neat principles that, it turns out, don’t necessarily apply to microscopic cells wriggling through sticky fluids.

At the recent annual International AIDS Conference, a startling presentation about the newest wonder drug in HIV prevention brought a raucous standing ovation.

But some of us in the public health community are now starting to wonder what all the cheering was about. Although the scientific results were impeccable, the process for translating those results into action for young women in Africa has been left to our imaginations. And if history is any guide, this could be a nightmare.

When the results first came out, Gilead, the manufacturer of lenacapavir, stated it was too early to discuss licensing and offering vague plans about its production and availability in Africa. Just recently, a second study among men who have sex with men and predominantly conducted in the Northern Hemisphere showed similarly promising results. While Gilead now says they have sufficient data to move ahead with licensing and manufacturing worldwide, they have offered no timeline to do so. Urgency to report trial results has not been mirrored by the urgency to provide access. Unanswered questions remain about why another study was needed to move ahead with approvals for use in African women, and if and when lenacapavir will be made available at an affordable price in the African region.

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