bims-longev Biomed News
on Longevity
Issue of 2023–04–23
eight papers selected by
Andreea Nitescu
  1. The Fountain of Youth: Gut Microbiome and Its Role in Healthy Aging.
  2. Fountain of youth-Targeting autophagy in aging.
  3. Multi-omic underpinnings of epigenetic aging and human longevity.
  4. High-Intensity interval training reduces transcriptomic age: A randomized controlled trial.
  5. Chow diet in mouse aging studies: nothing regular about it.
  6. The emerging role of lysine succinylation in ovarian aging.
  7. The hunger games as the key to happily ever after?
  8. Handgrip strength is positively associated with successful aging in older adults: A national cross-sectional study in China.
  1. Holist Nurs Pract. 2023 May-Jun 01;37(3):37(3): 172-173
    The Fountain of Youth: Gut Microbiome and Its Role in Healthy Aging.
    Stephanie Maxine Ross.
      
    DOI:  https://doi.org/10.1097/HNP.0000000000000585
  2. Front Aging Neurosci. 2023 ;15 1125739
    Fountain of youth-Targeting autophagy in aging.
    Lea Danics, Anna Anoir Abbas, Balázs Kis, Karolina Pircs.
      As our society ages inexorably, geroscience and research focusing on healthy aging is becoming increasingly urgent. Macroautophagy (referred to as autophagy), a highly conserved process of cellular clearance and rejuvenation has attracted much attention due to its universal role in organismal life and death. Growing evidence points to autophagy process as being one of the key players in the determination of lifespan and health. Autophagy inducing interventions show significant improvement in organismal lifespan demonstrated in several experimental models. In line with this, preclinical models of age-related neurodegenerative diseases demonstrate pathology modulating effect of autophagy induction, implicating its potential to treat such disorders. In humans this specific process seems to be more complex. Recent clinical trials of drugs targeting autophagy point out some beneficial effects for clinical use, although with limited effectiveness, while others fail to show any significant improvement. We propose that using more human-relevant preclinical models for testing drug efficacy would significantly improve clinical trial outcomes. Lastly, the review discusses the available cellular reprogramming techniques used to model neuronal autophagy and neurodegeneration while exploring the existing evidence of autophagy's role in aging and pathogenesis in human-derived in vitro models such as embryonic stem cells (ESCs), induced pluripotent stem cell derived neurons (iPSC-neurons) or induced neurons (iNs).
    Keywords:  aging; autophagy; autophagy-modifying drugs; clinical trial; direct reprogramming; disease modeling; neurodegenerative diseases; rejuvenation
    DOI:  https://doi.org/10.3389/fnagi.2023.1125739
  3. Nat Commun. 2023 04 19. 14(1): 2236
    Multi-omic underpinnings of epigenetic aging and human longevity.
    Lucas A Mavromatis, Daniel B Rosoff, Andrew S Bell, Jeesun Jung, Josephin Wagner, Falk W Lohoff.
      Biological aging is accompanied by increasing morbidity, mortality, and healthcare costs; however, its molecular mechanisms are poorly understood. Here, we use multi-omic methods to integrate genomic, transcriptomic, and metabolomic data and identify biological associations with four measures of epigenetic age acceleration and a human longevity phenotype comprising healthspan, lifespan, and exceptional longevity (multivariate longevity). Using transcriptomic imputation, fine-mapping, and conditional analysis, we identify 22 high confidence associations with epigenetic age acceleration and seven with multivariate longevity. FLOT1, KPNA4, and TMX2 are novel, high confidence genes associated with epigenetic age acceleration. In parallel, cis-instrument Mendelian randomization of the druggable genome associates TPMT and NHLRC1 with epigenetic aging, supporting transcriptomic imputation findings. Metabolomics Mendelian randomization identifies a negative effect of non-high-density lipoprotein cholesterol and associated lipoproteins on multivariate longevity, but not epigenetic age acceleration. Finally, cell-type enrichment analysis implicates immune cells and precursors in epigenetic age acceleration and, more modestly, multivariate longevity. Follow-up Mendelian randomization of immune cell traits suggests lymphocyte subpopulations and lymphocytic surface molecules affect multivariate longevity and epigenetic age acceleration. Our results highlight druggable targets and biological pathways involved in aging and facilitate multi-omic comparisons of epigenetic clocks and human longevity.
    DOI:  https://doi.org/10.1038/s41467-023-37729-w
  4. Aging Cell. 2023 Apr 20. e13841
    High-Intensity interval training reduces transcriptomic age: A randomized controlled trial.
    Trevor Lohman, Gurinder Bains, Steve Cole, Lida Gharibvand, Lee Berk, Everett Lohman.
      While the relationship between exercise and life span is well-documented, little is known about the effects of specific exercise protocols on modern measures of biological age. Transcriptomic age (TA) predictors provide an opportunity to test the effects of high-intensity interval training (HIIT) on biological age utilizing whole-genome expression data. A single-site, single-blinded, randomized controlled clinical trial design was utilized. Thirty sedentary participants (aged 40-65) were assigned to either a HIIT group or a no-exercise control group. After collecting baseline measures, HIIT participants performed three 10 × 1 HIIT sessions per week for 4 weeks. Each session lasted 23 min, and total exercise duration was 276 min over the course of the 1-month exercise protocol. TA, PSS-10 score, PSQI score, PHQ-9 score, and various measures of body composition were all measured at baseline and again following the conclusion of exercise/control protocols. Transcriptomic age reduction of 3.59 years was observed in the exercise group while a 3.29-years increase was observed in the control group. Also, PHQ-9, PSQI, BMI, body fat mass, and visceral fat measures were all improved in the exercise group. A hypothesis-generation gene expression analysis suggested exercise may modify autophagy, mTOR, AMPK, PI3K, neurotrophin signaling, insulin signaling, and other age-related pathways. A low dose of HIIT can reduce an mRNA-based measure of biological age in sedentary adults between the ages of 40 and 65 years old. Other changes in gene expression were relatively modest, which may indicate a focal effect of exercise on age-related biological processes.
    Keywords:  aging; autophagy; biological age; body composition; gene expression; high-intensity interval training; longevity; transcriptome
    DOI:  https://doi.org/10.1111/acel.13841
  5. Geroscience. 2023 Apr 20.
    Chow diet in mouse aging studies: nothing regular about it.
    Jennifer Lee, Chloe Purello, Sarah L Booth, Brian Bennett, Christopher D Wiley, Ron Korstanje.
      Chow diet is used in the majority of rodent studies and, although assumed to be standardized for dietary source and nutritional contents, it varies widely across commercial formulations. Similarly, current approaches to study aging in rodents involve a single-diet formulation across the lifespan and overlook age-specific nutritional requirements, which may have long-term effects on aging processes. Together, these nutrition-based disparities represent major gaps in geroscience research, affecting the interpretation and reproducibility of the studies. This perspective aims to raise awareness on the importance of rodent diet formulation and proposes that geroscientists include detailed descriptions of all experimental diets and feeding protocols. Detailed reporting of diets will enhance rigor and reproducibility of aging rodent studies and lead to more translational outcomes in geroscience research.
    Keywords:  Aging; Chow diet; Dietary source
    DOI:  https://doi.org/10.1007/s11357-023-00775-9
  6. Reprod Biol Endocrinol. 2023 Apr 20. 21(1): 38
    The emerging role of lysine succinylation in ovarian aging.
    Meiling Le, Jia Li, Dalei Zhang, Yuan Yuan, Chong Zhou, Jinxia He, Jian Huang, Liaoliao Hu, Tao Luo, Liping Zheng.
       BACKGROUND: Ovarian aging is a process of decline in its reserve leading to ovary dysfunction and even reduced health quality in offspring. However, aging-related molecular pathways in the ovary remain obscure. Lysine succinylation (Ksuc), a newly post-translational modification (PTM), has been found to be broadly conserved in both eukaryotic and prokaryotic cells, and associated with multiple pathophysiological processes. There are no relevant reports revealing a link between the molecular mechanisms of ovarian aging and Ksuc.
    METHODS: The level of Ksuc in ovaries of aged and premature ovarian insufficiency (POI) mice were detected by immunoblotting and immunohistochemical. To further explore the role of Ksuc in ovarian aging, using in vitro mouse ovary tissue culture and an in vivo mouse model with changed Ksuc level.
    RESULTS: Increased Ksuc in ovaries of aged and POI mice and distribution of Ksuc in various types of mice ovarian cells and the high level of Ksuc in granulosa cells (GCs) were revealed. Histological assessments and hormone levels analyses showed that the high Ksuc level down-regulated the ovarian index and the anti-Müllerian hormone (AMH) and estrogen levels, and increased follicular atresia. Moreover, in the high Ksuc groups, the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) intensities and the expression of Cleaved-caspase-3 increased and the expression of B-cell lymphoma-2 (Bcl-2) decreased together with positively-expressed P21, an aging-related marker. These results suggest that ovarian aging is likely associated with alteration in Ksuc.
    CONCLUSION: The present study has identified Ksuc in mouse ovary and found that high Ksuc level most likely contributes to ovarian aging which is expected further investigation to provide new information for delaying physiological ovarian aging and treating pathological ovarian aging.
    DOI:  https://doi.org/10.1186/s12958-023-01088-4
  7. J Gerontol A Biol Sci Med Sci. 2023 Apr 20. pii: glad100. [Epub ahead of print]
    The hunger games as the key to happily ever after?
    Jacques A Deere, Clarice Xu, Celestine Adelmant, Aziz Aboobaker, Roberto Salguero-Gómez.
      The world's human population is reaching record longevities. Consequently, our societies are experiencing the impacts of prolonged longevity, such as increased retirement age. A major hypothesised influence on ageing patterns is resource limitation, formalised under calorie restriction (CR) theory. This theory predicts extended organismal longevity due to reduced calorie intake without malnutrition. However, several challenges face current CR research and, although several attempts have been made to overcome these challenges, there is still a lack of holistic understanding of how CR shapes organismal vitality. Here, we conduct a literature review of 224 CR peer-reviewed publications to summarise the state-of-the-art in the field. Using this summary, we highlight challenges of CR research in our understanding of its impacts on longevity. We demonstrate that experimental research is biased towards short-lived species (98.2% of studies examine species with <5 years of mean life expectancy) and lacks realism in key areas, such as stochastic environments or interactions with other environmental drivers (e.g., temperature). We argue that only by considering a range of short- and long-lived species and taking more realistic approaches, can CR impacts on longevity be examined and validated in natural settings. We conclude by proposing experimental designs and study species that will allow the discipline to gain much-needed understanding of how restricting caloric intake affects long-lived species in realistic settings. Through incorporating more experimental realism, we anticipate crucial insights that will ultimately shape the myriad of socio-bio-economic impacts of senescence in humans and other species across the Tree of Life.
    Keywords:  Life history; longevity; senescence; stochastic environments
    DOI:  https://doi.org/10.1093/gerona/glad100
  8. J Affect Disord. 2023 Apr 19. pii: S0165-0327(23)00500-1. [Epub ahead of print]
    Handgrip strength is positively associated with successful aging in older adults: A national cross-sectional study in China.
    Xiaoguang Zhao, Siyuan Chen, Nan Liu, Fei Hu, Jiabin Yu.
       OBJECTIVES: Muscle strength gradually decreases with advancing age. This study aimed to explore the relationship between handgrip strength and successful aging and its specific dimensions in older adults using a nationally representative sample.
    METHODS: A total of 5269 adults aged 60 and older were included in this study. Handgrip strength was measured using a dynamometer and was organized into quartiles by sex. Successful aging was defined by Rowe and Kahn's conceptual model including the following five dimensions: (a) no major diseases; (b) freedom from disability; (c) high cognitive function; (d) good psychological status; and (e) active social engagement in life. Logistic regression models were used to examine the association between handgrip strength and successful aging and its specific dimensions.
    RESULTS: The prevalence of successful aging was found to be 35.1 % in Chinese older adults. Compared to older adults with handgrip strength in the first quartile, those with handgrip strength in the second quartile, third quartile, and fourth quartile had a higher probability of successful aging (adjusted odds ratio (OR): 1.40 (95 % CI: 1.16, 1.69) to 2.06 (95 % CI: 1.70, 2.50)). We further found that the association between handgrip strength and successful aging was related to different ages.
    CONCLUSION: This study suggested that there is a close association between handgrip strength and successful aging. Older adults who have greater handgrip strength can successfully deal with the challenges of aging. For older people, keeping a high level of muscle strength in late life may be helpful to the constant successful aging.
    Keywords:  Aging; China, elderly; Muscle strength; Successful
    DOI:  https://doi.org/10.1016/j.jad.2023.04.041
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