bims-longev Biomed News
on Longevity
Issue of 2023–04–30
thirteen papers selected by
Andreea Nitescu
  1. In vivo partial reprogramming alters age-associated molecular changes during physiological aging in mice.
  2. Pleiotropic effects of mitochondria in aging.
  3. Alpha-ketoglutarate supplementation ameliorates ovarian reserve and oocyte quality decline with aging in mice.
  4. Endogenous retroviruses and aging.
  5. Interaction between KLOTHO-VS Heterozygosity and APOE ε4 Allele Predicts Rate of Cognitive Decline in Late-Onset Alzheimer's Disease.
  6. Recognizing the importance of ovarian aging research.
  7. Mendelian randomization of genetically independent aging phenotypes identifies LPA and VCAM1 as biological targets for human aging.
  8. Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial.
  9. Identification of dual-purpose therapeutic targets implicated in aging and glioblastoma multiforme using PandaOmics - an AI-enabled biological target discovery platform.
  10. Exercise Programs Combined with Diet Supplementation Improve Body Composition and Physical Function in Older Adults with Sarcopenia: A Systematic Review.
  11. Is metformin neuroprotective against diabetes mellitus-induced neurodegeneration? An updated graphical review of molecular basis.
  12. NAD+ boosting brings tears to aging eyes.
  13. Nature's longevity marvels.
  1. Nat Aging. 2022 Mar;2(3): 243-253
    In vivo partial reprogramming alters age-associated molecular changes during physiological aging in mice.
    Kristen C Browder, Pradeep Reddy, Mako Yamamoto, Amin Haghani, Isabel Guillen Guillen, Sanjeeb Sahu, Chao Wang, Yosu Luque, Javier Prieto, Lei Shi, Kensaku Shojima, Tomoaki Hishida, Zijuan Lai, Qingling Li, Feroza K Choudhury, Weng R Wong, Yuxin Liang, Dewakar Sangaraju, Wendy Sandoval, Concepcion Rodriguez Esteban, Estrella Nuñez Delicado, Pedro Guillen Garcia, Michal Pawlak, Jason A Vander Heiden, Steve Horvath, Heinrich Jasper, Juan Carlos Izpisua Belmonte.
      Partial reprogramming by expression of reprogramming factors (Oct4, Sox2, Klf4 and c-Myc) for short periods of time restores a youthful epigenetic signature to aging cells and extends the life span of a premature aging mouse model. However, the effects of longer-term partial reprogramming in physiologically aging wild-type mice are unknown. Here, we performed various long-term partial reprogramming regimens, including different onset timings, during physiological aging. Long-term partial reprogramming lead to rejuvenating effects in different tissues, such as the kidney and skin, and at the organismal level; duration of the treatment determined the extent of the beneficial effects. The rejuvenating effects were associated with a reversion of the epigenetic clock and metabolic and transcriptomic changes, including reduced expression of genes involved in the inflammation, senescence and stress response pathways. Overall, our observations indicate that partial reprogramming protocols can be designed to be safe and effective in preventing age-related physiological changes. We further conclude that longer-term partial reprogramming regimens are more effective in delaying aging phenotypes than short-term reprogramming.
    DOI:  https://doi.org/10.1038/s43587-022-00183-2
  2. Nat Aging. 2022 Mar;2(3): 199-213
    Pleiotropic effects of mitochondria in aging.
    Tanes Lima, Terytty Yang Li, Adrienne Mottis, Johan Auwerx.
      Aging is typified by a progressive decline in mitochondrial activity and stress resilience. Here, we review how mitochondrial stress pathways have pleiotropic effects on cellular and systemic homeostasis, which can comprise protective or detrimental responses during aging. We describe recent evidence arguing that defects in these conserved adaptive pathways contribute to aging and age-related diseases. Signaling pathways regulating the mitochondrial unfolded protein response, mitochondrial membrane dynamics, and mitophagy are discussed, emphasizing how their failure contributes to heteroplasmy and de-regulation of key metabolites. Our current understanding of how these processes are controlled and interconnected explains how mitochondria can widely impact fundamental aspects of aging.
    DOI:  https://doi.org/10.1038/s43587-022-00191-2
  3. Mol Cell Endocrinol. 2023 Apr 23. pii: S0303-7207(23)00086-2. [Epub ahead of print] 111935
    Alpha-ketoglutarate supplementation ameliorates ovarian reserve and oocyte quality decline with aging in mice.
    Huan Wang, Jianmin Xu, Hui Li, Wenhui Chen, Xinxin Zeng, Yingpu Sun, Qingling Yang.
      Assisted reproductive technology is widely accepted as an effective treatment to improve female fertility, but the decline of aging oocyte quality remains an important factor in the decrease of female fecundity. However, the effective strategies for improving oocyte aging are still not well understood. In the study, we demonstrated that ROS content and abnormal spindle proportion were increased and mitochondrial membrane potential was decreased in aging oocytes. However, supplementation of α-ketoglutarate (α-KG), an immediate metabolite in the tricarboxylic acid cycle (TCA), for 4 months to aging mice, significantly increased the ovarian reserve showed by more follicle numbers observed. In addition, the oocyte quality was significantly improved, as demonstrated by reduced fragmentation rate and decreased reactive oxygen species (ROS) levels, in addition to a lower rate of abnormal spindle assembly, thereby improving the mitochondrial membrane potential. Consistent with the in vivo data, α-KG administration also improved the post-ovulated aging oocyte quality and early embryonic development by improving mitochondrial functions and reducing ROS accumulation and abnormal spindle assembly. Our data revealed that α-KG supplementation might be an effective strategy to improve the quality of aging oocytes in vivo or in vitro.
    Keywords:  Oocyte aging; Ovarian aging; Oxidative stress; α-ketoglutarate
    DOI:  https://doi.org/10.1016/j.mce.2023.111935
  4. Nat Aging. 2023 Feb;3(2): 145
    Endogenous retroviruses and aging.
    Sebastien Thuault.
      
    DOI:  https://doi.org/10.1038/s43587-023-00377-2
  5. Genes (Basel). 2023 Apr 15. pii: 917. [Epub ahead of print]14(4):
    Interaction between KLOTHO-VS Heterozygosity and APOE ε4 Allele Predicts Rate of Cognitive Decline in Late-Onset Alzheimer's Disease.
    Xi Richard Chen, Yongzhao Shao, Martin J Sadowski, On Behalf Of The Alzheimer's Disease Neuroimaging Initiative.
      KLOTHO-VS heterozygosity (KL-VShet+) promotes longevity and protects against cognitive decline in aging. To determine whether KL-VShet+ mitigates Alzheimer's disease (AD) progression, we used longitudinal linear-mixed models to compare the rate of change in multiple cognitive measures in AD patients stratified by APOE ε4 carrier status. We aggregated data on 665 participants (208 KL-VShet-/ε4-, 307 KL-VShet-/ε4+, 66 KL-VShet+/ε4-, and 84 KL-VShet+/ε4+) from two prospective cohorts, the National Alzheimer's Coordinating Center and the Alzheimer's Disease Neuroimaging Initiative. All participants were initially diagnosed with mild cognitive impairment, later developed AD dementia during the study, and had at least three subsequent visits. KL-VShet+ conferred slower cognitive decline in ε4 non-carriers (+0.287 MMSE points/year, p = 0.001; -0.104 CDR-SB points/year, p = 0.026; -0.042 ADCOMS points/year, p < 0.001) but not in ε4 carriers who generally had faster rates of decline than non-carriers. Stratified analyses showed that the protective effect of KL-VShet+ was particularly prominent in male participants, those who were older than the median baseline age of 76 years, or those who had an education level of at least 16 years. For the first time, our study provides evidence that KL-VShet+ status has a protective effect on AD progression and interacts with the ε4 allele.
    Keywords:  APOE; Alzheimer’s disease; KLOTHO; aging; cognitive decline
    DOI:  https://doi.org/10.3390/genes14040917
  6. Nat Aging. 2022 Dec;2(12): 1071-1072
    Recognizing the importance of ovarian aging research.
      
    DOI:  https://doi.org/10.1038/s43587-022-00339-0
  7. Nat Aging. 2022 Jan;2(1): 19-30
    Mendelian randomization of genetically independent aging phenotypes identifies LPA and VCAM1 as biological targets for human aging.
    Biobank Japan Project
      Length and quality of life are important to us all, yet identification of promising drug targets for human aging using genetics has had limited success. In the present study, we combine six European-ancestry genome-wide association studies of human aging traits-healthspan, father and mother lifespan, exceptional longevity, frailty index and self-rated health-in a principal component framework that maximizes their shared genetic architecture. The first principal component (aging-GIP1) captures both length of life and indices of mental and physical wellbeing. We identify 27 genomic regions associated with aging-GIP1, and provide additional, independent evidence for an effect on human aging for loci near HTT and MAML3 using a study of Finnish and Japanese survival. Using proteome-wide, two-sample, Mendelian randomization and colocalization, we provide robust evidence for a detrimental effect of blood levels of apolipoprotein(a) and vascular cell adhesion molecule 1 on aging-GIP1. Together, our results demonstrate that combining multiple aging traits using genetic principal components enhances the power to detect biological targets for human aging.
    DOI:  https://doi.org/10.1038/s43587-021-00159-8
  8. Nat Aging. 2023 Mar;3(3): 248-257
    Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial.
    R Waziry, C P Ryan, D L Corcoran, K M Huffman, M S Kobor, M Kothari, G H Graf, V B Kraus, W E Kraus, D T S Lin, C F Pieper, M E Ramaker, M Bhapkar, S K Das, L Ferrucci, W J Hastings, M Kebbe, D C Parker, S B Racette, I Shalev, B Schilling, D W Belsky.
      The geroscience hypothesis proposes that therapy to slow or reverse molecular changes that occur with aging can delay or prevent multiple chronic diseases and extend healthy lifespan1-3. Caloric restriction (CR), defined as lessening caloric intake without depriving essential nutrients4, results in changes in molecular processes that have been associated with aging, including DNA methylation (DNAm)5-7, and is established to increase healthy lifespan in multiple species8,9. Here we report the results of a post hoc analysis of the influence of CR on DNAm measures of aging in blood samples from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial, a randomized controlled trial in which n = 220 adults without obesity were randomized to 25% CR or ad libitum control diet for 2 yr (ref. 10). We found that CALERIE intervention slowed the pace of aging, as measured by the DunedinPACE DNAm algorithm, but did not lead to significant changes in biological age estimates measured by various DNAm clocks including PhenoAge and GrimAge. Treatment effect sizes were small. Nevertheless, modest slowing of the pace of aging can have profound effects on population health11-13. The finding that CR modified DunedinPACE in a randomized controlled trial supports the geroscience hypothesis, building on evidence from small and uncontrolled studies14-16 and contrasting with reports that biological aging may not be modifiable17. Ultimately, a conclusive test of the geroscience hypothesis will require trials with long-term follow-up to establish effects of intervention on primary healthy-aging endpoints, including incidence of chronic disease and mortality18-20.
    DOI:  https://doi.org/10.1038/s43587-022-00357-y
  9. Aging (Albany NY). 2023 Apr 26. 15
    Identification of dual-purpose therapeutic targets implicated in aging and glioblastoma multiforme using PandaOmics - an AI-enabled biological target discovery platform.
    Andrea Olsen, Zachary Harpaz, Christopher Ren, Anastasia Shneyderman, Alexander Veviorskiy, Maria Dralkina, Simon Konnov, Olga Shcheglova, Frank W Pun, Geoffrey Ho Duen Leung, Hoi Wing Leung, Ivan V Ozerov, Alex Aliper, Mikhail Korzinkin, Alex Zhavoronkov.
      Glioblastoma Multiforme (GBM) is the most aggressive and most common primary malignant brain tumor. The age of GBM patients is considered as one of the disease's negative prognostic factors and the mean age of diagnosis is 62 years. A promising approach to preventing both GBM and aging is to identify new potential therapeutic targets that are associated with both conditions as concurrent drivers. In this work, we present a multi-angled approach of identifying targets, which takes into account not only the disease-related genes but also the ones important in aging. For this purpose, we developed three strategies of target identification using the results of correlation analysis augmented with survival data, differences in expression levels and previously published information of aging-related genes. Several studies have recently validated the robustness and applicability of AI-driven computational methods for target identification in both cancer and aging-related diseases. Therefore, we leveraged the AI predictive power of the PandaOmics TargetID engine in order to rank the resulting target hypotheses and prioritize the most promising therapeutic gene targets. We propose cyclic nucleotide gated channel subunit alpha 3 (CNGA3), glutamate dehydrogenase 1 (GLUD1) and sirtuin 1 (SIRT1) as potential novel dual-purpose therapeutic targets to treat aging and GBM.
    Keywords:  GBM; PandaOmics; aging; glioblastoma; target discovery
    DOI:  https://doi.org/10.18632/aging.204678
  10. Nutrients. 2023 Apr 21. pii: 1998. [Epub ahead of print]15(8):
    Exercise Programs Combined with Diet Supplementation Improve Body Composition and Physical Function in Older Adults with Sarcopenia: A Systematic Review.
    Marco Antonio Hernández-Lepe, Michelle Itzel Miranda-Gil, Edith Valbuena-Gregorio, Francisco Javier Olivas-Aguirre.
      Sarcopenia is a progressive and frequent syndrome among older adults highly related to physical inactivity and malnutrition. Nowadays, it is considered a pathology that triggers multiple health complications associated with the loss of muscle mass, strength, autonomy, and quality of life. The objective of the present systematic review was to evaluate the effect of exercise programs combined with dietary supplementation on body composition as the primary outcome. This systematic review was carried out in accordance with the elements considered for planning a systematic review by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and the search was performed in the Scopus, EBSCO, and PubMed databases for the last 10 years. A total of 16 studies met the inclusion criteria and were included in this systematic review. Regular resistance exercise together with daily essential amino acids or whey protein and vitamin D supplementation improve the maintenance or gains in appendiceal/skeletal muscle mass and total lean mass in sarcopenic older adults. The data suggest a synergistic effect not only on the primary outcome, but also on other variables such as strength, speed, stability, and other indicators of quality of life. This systematic review was registered in PROSPERO, ID: CRD42022344284.
    Keywords:  elderly; exercise; food supplementation; physical activity; protein; sarcopenia
    DOI:  https://doi.org/10.3390/nu15081998
  11. Pharmacol Rep. 2023 Apr 24.
    Is metformin neuroprotective against diabetes mellitus-induced neurodegeneration? An updated graphical review of molecular basis.
    Fatemeh Karami, Hamidreza Jamaati, Natalie Coleman-Fuller, Maryam Shokrian Zeini, A Wallace Hayes, Mina Gholami, Mahsa Salehirad, Mohammad Darabi, Majid Motaghinejad.
      Diabetes mellitus (DM) is a metabolic disease that activates several molecular pathways involved in neurodegenerative disorders. Metformin, an anti-hyperglycemic drug used for treating DM, has the potential to exert a significant neuroprotective role against the detrimental effects of DM. This review discusses recent clinical and laboratory studies investigating the neuroprotective properties of metformin against DM-induced neurodegeneration and the roles of various molecular pathways, including mitochondrial dysfunction, oxidative stress, inflammation, apoptosis, and its related cascades. A literature search was conducted from January 2000 to December 2022 using multiple databases including Web of Science, Wiley, Springer, PubMed, Elsevier Science Direct, Google Scholar, the Core Collection, Scopus, and the Cochrane Library to collect and evaluate peer-reviewed literature regarding the neuroprotective role of metformin against DM-induced neurodegenerative events. The literature search supports the conclusion that metformin is neuroprotective against DM-induced neuronal cell degeneration in both peripheral and central nervous systems, and this effect is likely mediated via modulation of oxidative stress, inflammation, and cell death pathways.
    Keywords:  Diabetes mellitus; Metformin; Neurodegeneration; Neuroprotection
    DOI:  https://doi.org/10.1007/s43440-023-00469-1
  12. Nat Aging. 2022 Feb;2(2): 97-99
    NAD+ boosting brings tears to aging eyes.
    Mitsukuni Yoshida, Rajendra S Apte.
      
    DOI:  https://doi.org/10.1038/s43587-022-00172-5
  13. Nat Aging. 2022 Jul;2(7): 564
    Nature's longevity marvels.
    Anna Kriebs.
      
    DOI:  https://doi.org/10.1038/s43587-022-00249-1
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