An extract of Rosaceae, Solanaceae and Zingiberaceae increases health span and mobility in Caenorhabditis elegans

Background Members of the Rosaceae, Solanaceae and Zingiberaceae families which include fruits such as cherries, tomatoes and ginger are known to have health promoting effects. There is growing interest in consuming these “functional foods” as a means to increase health and healthy ageing. However, many studies explore the effect of these foods in isolation, not as a blend of multiple functional foods. Methods In this study, an extract containing the dried berries, fruits, and roots of members of these families was prepared, which we called Bioact®180. The nematode Caenorhabditis elegans was used to evaluate the effects of Bioact®180 on lifespan and health endpoints, including muscle and mitochondria structure and locomotion. Results Exposure to the 1000 µg/mL of Bioact®180 extract, containing 4% total phenols, were healthier, as observed by an increase in mean lifespan with and small but significant increase in maximal lifespan. Nematodes exposed to Bioact®180 displayed better mobility in mid-life stages as well as enhanced mitochondrial morphology, which was more comparable to younger animals, suggesting that these worms are protected to some degree from sarcopenia. Conclusions Together, our findings reveal that Bioact®180, a blend of fruits and roots from Rosaceae, Solanaceae and Zingiberaceae family members has anti-aging effects. Bioact®180 promotes health and lifespan extension in C. elegans, corresponding to functional improvements in mobility.

Metabolism, Microbiota-Host Interactions, Aging and Stress Response: Diagnostic and Therapeutic Applications of the Physiological Fitness Landscape

Using methods first developed in the physical sciences and adapting them to medicine and physiology, as is proposed here regarding the Physiological Fitness Landscape, can be a powerful tool in the management of disease and in the maintenance of long health span.

Translational Geroscience: Human Models of Healthy Aging and Longevity

While insulin like growth factor-1 (IGF-1) is a well-established modulator of aging and longevity in model organisms, its role in humans is less well understood. Previous ambiguities in part have been attributed to cohort characteristics and unawareness of interactions between age and IGF-1. Centenarians have emerged as an ideal model of healthy aging because they delay the onset of age-related diseases and often remain disease free for the duration of their lifespan. In cohorts of centenarians and generally healthy older adults, we demonstrated that reduced IGF-1 is associated with extended lifespan and health-span. Additionally, we confirmed that IGF-1 interacts with age to modify risk in a manner consistent with antagonistic pleiotropy: younger individuals with high IGF-1 are protected from dementia, vascular disease, diabetes, cancer, and osteoporosis, while older individuals do not exhibit IGF-1-associated protection from disease. These findings offer evidence for IGF-1 modulating health-span and lifespan in humans.

The Rise and the Death of Senescent Cells: From Mechanisms to Interventions

Aging is at the root of age-related diseases and therapies targeting basic age-associated mechanisms have the potential to extend healthy lifespan. A common feature of older organisms is the accumulation of senescent cells – cells that have irreversibly lost the capacity to undergo replication. Senescent cells are characterized by an irreversible cell cycle arrest and by the Senescence-Associated Secretory Phenotype (SASP), which include many tissue remodeling and pro-inflammatory factors. Senescent cells are intermittently present during embryogenesis and in young organisms. On the contrary senescent cells accumulate and persist in aging tissues. Significantly, these persistent senescent cells can drive low-grade chronic inflammation, and their genetic or pharmacological elimination is sufficient to delay a number of diseases and to improve health span. Here, I will discuss the mechanisms by which senescent cells can promote tissue aging and dysfunction and the potential of targeting senescent cells to delay human aging.

Ageing and rejuvenation models reveal changes in key microbial communities associated with healthy ageing

Background The gut microbiota is associated with diverse age-related disorders. Several rejuvenation methods, such as probiotic administration and faecal microbiota transplantation, have been applied to alter the gut microbiome and promote healthy ageing. Nevertheless, prolongation of the health span of aged mice by remodelling the gut microbiome remains challenging. Results Here, we report the changes in gut microbial communities and their functions in mouse models during ageing and three rejuvenation procedures including co-housing, serum-injection and parabiosis. Our results showed that the compositional structure and gene abundance of the intestinal microbiota changed dynamically during the ageing process. Through the three rejuvenation procedures, we observed that the microbial community and intestinal immunity of aged mice were comparable to those of young mice. The results of metagenomic data analysis underscore the importance of the high abundance of Akkermansia and the butyrate biosynthesis pathway in the rejuvenated mouse group. Furthermore, oral administration of Akkermansia sufficiently ameliorated the senescence-related phenotype in the intestinal systems in aged mice and extended the health span, as evidenced by the frailty index and restoration of muscle atrophy. Conclusions In conclusion, the changes in key microbial communities and their functions during ageing and three rejuvenation procedures, and the increase in the healthy lifespan of aged mice by oral administration of Akkermansia. Our results provide a rationale for developing therapeutic strategies to achieve healthy active ageing.

Sex-Specific Associations of Testosterone and Genetic Factors With Health Span

BackgroundPrevious studies have suggested associations between testosterone, genetic factors, and a series of complex diseases, but the associations with the lifespan phenotype, such as health span, remain unclear.MethodsIn this prospective cohort study, we analyzed 145,481 men and 147,733 women aged 38–73 years old from UK Biobank (UKB) to investigate the sex-specific associations of total testosterone (TT), free testosterone (FT), or polygenic risk score (PRS) with health span termination (HST) risk. At baseline, serum testosterone levels were measured. HST was defined by eight events strongly associated with longevity. PRS, an efficient tool combining the effect of common genetic variants to discriminate genetic risk of complex phenotypes, was constructed by 12 single-nucleotide polymorphisms related to health span from UKB (P ≤ 5.0 × 10−8). We used multivariable Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsWith a median follow-up time of 7.70 years, 26,748 (18.39%) men and 18,963 (12.84%) women had HST. TT was negatively associated with HST in men [HR per standard deviation (SD) increment of log-TT: 0.92, 95% CI: 0.88–0.97]. Inversely, both TT (HR per SD increment of log-TT: 1.05, 95% CI: 1.02–1.08) and FT (HR per SD increment of log-FT: 1.08, 95% CI: 1.05–1.11) presented an increased risk of HST in women. PRS was positively associated with HST risk (quintile 5 versus quintile 1, men, HR: 1.19, 95% CI: 1.15–1.24; women, HR: 1.21, 95% CI: 1.16–1.27). Moreover, men with high TT and low genetic risk showed the lowest HST risk (HR: 0.80, 95% CI: 0.73–0.88), whereas HST risk for women with both high TT and genetic risk increased obviously (HR: 1.32, 95% CI: 1.19–1.46). Similar joint effects were observed for FT in both genders.ConclusionsWe observed sex-specific associations that testosterone was negatively associated with HST risk in men and positively associated with HST risk in women. Genetic factors increased the HST risk, suggesting that participants with both high genetic risk and abnormal testosterone levels (high level in women or low level in men) should be the target for early intervention. Although our findings highlight the associations between testosterone and health span, further mechanistic studies and prospective trials are warranted to explore the causation behind.

Aging in the Digital Age: Using Technology to Increase the Reach of the Clinician Expert and Close the Gap Between Health Span and Life Span

Age-related cognitive impairment (ARCI) has a profound impact on individuals, families, health care systems, and societies at large. Evidence suggests that ARCI is the consequence of underlying brain pathology. Therefore, efforts to minimize the impact of ARCI and thus closing the gap between health span and life span, which has widened in recent years, requires early detection and timely deployment of targeted, personalized interventions. Access to clinical experts is limited and technology screening and assessment methods are thus appealing. However, as traditionally implemented patients were deprived of the benefit of personalized connection with a clinician, which is particularly critical for the prescription and to ensure the adherence to and ultimate success of therapeutic interventions. We present the concept of Intelligent Technology Therapy Assistant (ITA) as a scalable solution that increases the reach of clinical experts while sustaining the personal connection between each patient and their clinician. We illustrate ITA with the “Guttman Neuro Personal Trainer”®, a tele-rehabilitation platform that provides neuropsychological evaluation and care, and the Barcelona Brain Health Initiative (BBHI) multimodal intervention coaching app, a mobile-based platform that provides lifestyle coaching support in domains related to brain health. In addition, we discuss the translation of these models to a large-scale enterprise with Linus Health. To this end, we conclude with a discussion of challenges and opportunities to move the field forward.

Temporal Transcriptomics of Gut Escherichia coli in Caenorhabditis elegans Models of Aging

Previous research has reported effects of the microbiome on health span and life span of Caenorhabditis elegans , including interactions with evolutionarily conserved pathways in humans. We build on this literature by reporting the gene expression of Escherichia coli OP50 in wild-type (N2) and three long-lived mutants of C. elegans .