bims-longev 2023-03-26 papers

bims-longev

Biomed News

on Longevity

Issue of 2023–03–26
eleven papers selected by
Andreea Nitescu

Towards AI-driven longevity research: An overview.
Exploring the secrets of super-aging: a UK Biobank study on brain health and cognitive function.
Age-Associated Abnormalities of Water Homeostasis.
Alpha-ketoglutarate as a potent regulator for lifespan and healthspan: Evidences and perspectives.
Sex differences in adult lifespan and aging rate across mammals: a test of the 'Mother Curse hypothesis'.
Thyroid and Aging.
Potential reversal of biological age in women following an 8-week methylation-supportive diet and lifestyle program: a case series.
Research progress of circular RNA molecules in aging and age-related diseases.
Vanillic acid improves stress resistance and substantially extends lifespan in Caenorhabditis elegans.
Growth Hormone and Aging.
The Efficacy of Sodium-Glucose Cotransporter-2 Inhibitors in Improving Morbidity and Mortality of Heart Failure: A Systematic Review.

Front Aging. 2023 ;4 1057204

Towards AI-driven longevity research: An overview.

Nicola Marino, Guido Putignano, Simone Cappilli, Emmanuele Chersoni, Antonella Santuccione, Giuliana Calabrese, Evelyne Bischof, Quentin Vanhaelen, Alex Zhavoronkov, Bryan Scarano, Alessandro D Mazzotta, Enrico Santus.

  While in the past technology has mostly been utilized to store information about the structural configuration of proteins and molecules for research and medical purposes, Artificial Intelligence is nowadays able to learn from the existing data how to predict and model properties and interactions, revealing important knowledge about complex biological processes, such as aging. Modern technologies, moreover, can rely on a broader set of information, including those derived from the next-generation sequencing (e.g., proteomics, lipidomics, and other omics), to understand the interactions between human body and the external environment. This is especially relevant as external factors have been shown to have a key role in aging. As the field of computational systems biology keeps improving and new biomarkers of aging are being developed, artificial intelligence promises to become a major ally of aging research.

Keywords:  artificial intelligence; biomarkers; deep aging clock; feature selection; longevity medicine; machine learning

DOI:  https://doi.org/10.3389/fragi.2023.1057204
Geroscience. 2023 Mar 22.

Exploring the secrets of super-aging: a UK Biobank study on brain health and cognitive function.

Brandon S Klinedinst, Mihir K Kharate, Parvin Mohammadiarvejeh, Mohammad Fili, Amy Pollpeter, Brittany A Larsen, Shannin Moody, Qian Wang, Karin Allenspach, Jonathan P Mochel, Auriel A Willette.

  Communities across the globe are faced with a rapidly aging society, where age is the main risk factor for cognitive decline and development of Alzheimer's and related diseases. Despite extensive research, there have been no successful treatments yet. A rare group of individuals called "super-agers" have been noted to thrive with their exceptional ability to maintain a healthy brain and normal cognitive function even in old age. Studying their traits, lifestyles, and environments may provide valuable insight. This study used a data-driven approach to identify potential super-agers among 7121 UK Biobank participants and found that these individuals have the highest total brain volume, best cognitive performance, and lowest functional connectivity. The researchers suggest a novel hypothesis that these super-agers possess enhanced neural processing efficiency that increases with age and introduce a definition of the "neural efficiency index." Furthermore, several other types of aging were identified and significant structural-functional differences were observed between them, highlighting the benefit of research efforts in personalized medicine and precision nutrition.

Keywords:  Cognitive reserve; Healthy brain aging; Longitudinal study; Neural efficiency; Neurodegeneration; Neuroimaging

DOI:  https://doi.org/10.1007/s11357-023-00765-x
Endocrinol Metab Clin North Am. 2023 06;pii: S0889-8529(22)00109-8. [Epub ahead of print]52(2): 277-293

Age-Associated Abnormalities of Water Homeostasis.

Laura E Cowen, Steven P Hodak, Joseph G Verbalis.

  Deficits in renal function, thirst, and responses to osmotic and volume stimulation have been repeatedly demonstrated in older populations. The lessons learned over the past six decades serve to emphasize the fragile nature of water balance characteristic of aging. Older individuals are at increased risk for disturbances of water homeostasis due to both intrinsic disease and iatrogenic causes. These disturbances have real-life clinical implications in terms of neurocognitive effects, falls, hospital readmission and need for long-term care, incidence of bone fracture, osteoporosis, and mortality.

Keywords:  Aging; Arginine vasopressin; Diabetes insipidus; Hypernatremia; Hyponatremia; Osmolality; SIAD; Thirst

DOI:  https://doi.org/10.1016/j.ecl.2022.11.002
Exp Gerontol. 2023 Mar 20. pii: S0531-5565(23)00075-X. [Epub ahead of print]175 112154

Alpha-ketoglutarate as a potent regulator for lifespan and healthspan: Evidences and perspectives.

Saghi Hakimi Naeini, Laleh Mavaddatiyan, Zahra Rashid Kalkhoran, Soroush Taherkhani, Mahmood Talkhabi.

  Aging is a natural process that determined by a functional decline in cells and tissues as organisms are growing old, resulting in an increase at risk of disease and death. To this end, many efforts have been made to control aging and increase lifespan and healthspan. These efforts have led to the discovery of several anti-aging drugs and compounds such as rapamycin and metformin. Recently, alpha-ketoglutarate (AKG) has been introduced as a potential anti-aging metabolite that can control several functions in organisms, thereby increases longevity and improves healthspan. Unlike other synthetic anti-aging drugs, AKG is one of the metabolites of the tricarboxylic acid (TCA) cycle, also known as the Krebs cycle, and synthesized in the body. It plays a crucial role in the cell energy metabolism, amino acid/protein synthesis, epigenetic regulation, stemness and differentiation, fertility and reproductive health, and cancer cell behaviors. AKG exerts its effects through different mechanisms such as inhibiting mTOR and ATP-synthase, modulating DNA and histone demethylation and reducing ROS formation. Herein, we summarize the recent findings of AKG-related lifespan and healthspan studies and discuss AKG associated cell and molecular mechanisms involved in increasing longevity, improving reproduction, and modulating stem cells and cancer cells behavior. We also discuss the promises and limitations of AKG for delaying aging and other potential applications.

Keywords:  ATP synthesis; Aging; Alpha-ketoglutarate; DNA methylation; Healthspan; Lifespan; mTOR

DOI:  https://doi.org/10.1016/j.exger.2023.112154
Mech Ageing Dev. 2023 Mar 20. pii: S0047-6374(23)00025-8. [Epub ahead of print] 111799

Sex differences in adult lifespan and aging rate across mammals: a test of the 'Mother Curse hypothesis'.

Hugo Cayuela, Jean-Michel Gaillard, Cristina Vieira, Victor Ronget, Jérôme M W Gippet, Thamar Conde Garcia, Gabriel A B Marais, Jean-François Lemaître.

  In many animal species, including humans, males have shorter lifespan and show faster survival aging than females. This differential increase in mortality between sexes could result from the accumulation of deleterious mutations in the mitochondrial genome of males due to the maternal mode of mtDNA inheritance. To date, empirical evidence supporting the existence of this mechanism - called the Mother Curse hypothesis - remains largely limited to a few study cases in humans and Drosophila. In this study, we tested whether the Mother Curse hypothesis accounts for sex differences in lifespan and aging rate across 128 populations of mammals (60 and 68 populations studied in wild and captive conditions, respectively) encompassing 104 species. We found that adult lifespan decreases with increasing mtDNA neutral substitution rate in both sexes in a similar way in the wild - but not in captivity. Moreover, the aging rate marginally increased with neutral substitution rate in males and females in the wild. Overall, these results indicate that the Mother Curse hypothesis is not supported across mammals. We further discuss the implication of these findings for our understanding of the evolution of sex differences in mortality and aging.

Keywords:  longevity; mitochondria; mutation; senescence; sex

DOI:  https://doi.org/10.1016/j.mad.2023.111799
Endocrinol Metab Clin North Am. 2023 06;pii: S0889-8529(22)00104-9. [Epub ahead of print]52(2): 229-243

Thyroid and Aging.

Jennifer S R Mammen.

  Older adults are more vulnerable to the negative effects of excess thyroid hormone and may even be protected by lower levels of thyroid hormone. The diagnosis and management of thyroid disease in older adults needs to account for aging-related changes in function and resilliance.

Keywords:  HPT axis; Hyperthyroidism; Hypothyroidism; Thyroid homeostasis; Thyroid hormone therapy; Thyrotoxicosis

DOI:  https://doi.org/10.1016/j.ecl.2022.10.008
Aging (Albany NY). 2023 03 22. 15

Potential reversal of biological age in women following an 8-week methylation-supportive diet and lifestyle program: a case series.

Kara N Fitzgerald, Tish Campbell, Suzanne Makarem, Romilly Hodges.

  Here we report on a case series of six women who completed a methylation-supportive diet and lifestyle program designed to impact DNA methylation and measures of biological aging. The intervention consisted of an 8-week program that included diet, sleep, exercise and relaxation guidance, supplemental probiotics and phytonutrients and nutritional coaching. DNA methylation and biological age analysis (Horvath DNAmAge clock (2013), normalized using the SeSAMe pipeline [a]) was conducted on blood samples at baseline and at the end of the 8-week period. Five of the six participants exhibited a biological age reduction of between 1.22 and 11.01 years from their baseline biological age. There was a statistically significant (p=.039) difference in the participants' mean biological age before (55.83 years) and after (51.23 years) the 8-week diet and lifestyle intervention, with an average decrease of 4.60 years. The average chronological age at the start of the program was 57.9 years and all but one participant had a biological age younger than their chronological age at the start of the program, suggesting that biological age changes were unrelated to disease improvement and instead might be attributed to underlying aging mechanisms.

Keywords:  DNA methylation; aging; biological clock; epigenetic; lifestyle

DOI:  https://doi.org/10.18632/aging.204602
Ageing Res Rev. 2023 Mar 17. pii: S1568-1637(23)00072-7. [Epub ahead of print]87 101913

Research progress of circular RNA molecules in aging and age-related diseases.

Zhidan Zhang, Yuling Huang, AYao Guo, Lina Yang.

  Circular RNAs (circRNAs) are a class of single-chain endogenous closed circular RNAs that do not have a poly(A) tail at the 3' end and a cap structure at the 5' end and are connected end-to-end by covalent bonds. CircRNAs, which are pervasive, diverse, stable, and conversed, have functions in transcriptional control and protein translation and play vital roles in modulating cell senescence, individual aging, as well as the occurrence and development of age-related diseases. Studies in recent years were reviewed from aspects including the biosynthesis mechanisms, classification, expression, biomedical functions, associations with aging and age-related diseases, and potential clinical applications of circRNAs. It will provide the theoretic basis for exploring the molecular biological mechanisms of aging, using circRNA as the therapeutic target to delay aging, and finding therapeutic strategies to prevent and treat age-related diseases.

Keywords:  Age-related diseases; Aging; Biomedical functions; Characteristics; CircRNAs

DOI:  https://doi.org/10.1016/j.arr.2023.101913
J Gerontol A Biol Sci Med Sci. 2023 Mar 21. pii: glad086. [Epub ahead of print]

Vanillic acid improves stress resistance and substantially extends lifespan in Caenorhabditis elegans.

Ixchel Osorio-Paz, Xareni Valle-Jiménez, Regina Brunauer, Silvestre Alavez.

  Aging is the root cause of several pathologies like neurological and cardiovascular diseases. Identifying compounds that improve healthspan and extend lifespan, called geroprotectors, could be crucial to preventing or at least delaying the onset of age-related diseases. In this regard, the nematode Caenorhabditis elegans (C. elegans) is emerging as an easy, efficient, low-cost model system to screen natural products and identify novel geroprotectors. Phenolic acids can be found in a wide range of natural products that are part of the human diet. Vanillic acid is a phenolic acid that has previously been attributed with antioxidant, anti-inflammatory, and neuroprotective features. To determine whether these beneficial health effects amount to an extension of healthspan and lifespan, in this work, we thoroughly explore the effect of vanillic acid on C. elegans stress resistance and lifespan. We found that vanillic acid increases thermotolerance (19.4%), reduces protein aggregation (between 30 and 40%), improves motility, and extends lifespan by almost 50%, an extent hardly ever achieved with a natural compound. The increased thermotolerance induced by vanillic acid is independent of the insulin/IGF-1 signaling pathway but requires HSF-1 and is associated with increased HSP-4 and hsp-16.2 expression. These results provide new insight into understanding the therapeutical properties of vanillic acid and warrant further investigation of vanillic acid as a novel geroprotector.

Keywords:  Phenolic acids; geroprotectors; longevity; stress resistance; worm models of disease

DOI:  https://doi.org/10.1093/gerona/glad086
Endocrinol Metab Clin North Am. 2023 06;pii: S0889-8529(22)00097-4. [Epub ahead of print]52(2): 245-257

Growth Hormone and Aging.

Camille Hage, Roberto Salvatori.

  Growth hormone (GH) secretion declines with aging (somatopause). One of the most controversial issues in aging is GH treatment of older adults without evidence of pituitary pathology. Although some clinicians have proposed reversing the GH decline in the older population, most information comes from not placebo-controlled studies. Although most animal studies reported an association between decreased GH levels (or GH resistance) and increased lifespan, human models have shown contradictory reports on the consequences of GH deficiency (GHD) on longevity. Currently, GH treatment in adults is only indicated for individuals with childhood-onset GHD transitioning to adulthood or new-onset GHD due to hypothalamic or pituitary pathologic processes.

Keywords:  GH deficiency; GH resistance; Growth hormone; Human aging; Somatopause

DOI:  https://doi.org/10.1016/j.ecl.2022.10.003
Cureus. 2023 Feb;15(2): e34942

The Efficacy of Sodium-Glucose Cotransporter-2 Inhibitors in Improving Morbidity and Mortality of Heart Failure: A Systematic Review.

Suvedha Thiagaraj, Twisha S Shukla, Sai Dheeraj Gutlapalli, Hadi Farhat, Huma Irfan, Kanmani Muthiah, Namratha Pallipamu, Sogand Taheri, Safeera Khan.

  Cardiovascular disease (CVD) is the leading cause of mortality in patients with type 2 diabetes mellitus (DM) worldwide. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) were initially developed for treating patients with type 2 DM. The four major drugs developed are canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin. Apart from treating DM, these drugs have shown to have a beneficial effect on lowering cardiovascular death and lowering hospital admission, and have beneficial renal outcomes. Recently, several large-scale randomized controlled trials (RCTs) were done to assess the benefit of these drugs, mainly in patients with CVD, irrespective of their diabetic status. This systematic review examined seven large-scale randomized controlled trials that focused mainly on CVD in patients with type 2 DM and if it showed any improvement. We properly screened the RCTs if they demonstrated cardiovascular outcomes after taking the SGLT2i or a placebo drug. The seven studies combined had a total sample population of 55,433, and the mean follow-up time was about four years. The participants included in this study had various basal metabolic indices, ages, glomerular filtration rates, and diabetic status characteristics. Although these patients were quite different, after the administration of SGLT2i, the studies showed a beneficial effect in reducing CVD mortality and morbidity in patients with type 2 DM.

Keywords:  canagliflozin; cardiovascular disease; coronary artery disease; dapagliflozin; diastolic heart failure; empagliflozin; myocardial infarction; sglt2 inhibitor; systolic heart failure

DOI:  https://doi.org/10.7759/cureus.34942