bims-longev 2023-03-19 papers

bims-longev

Biomed News

on Longevity

Issue of 2023‒03‒19
eleven papers selected by
Andreea Nitescu

Four anti-aging drugs and calorie-restricted diet produce parallel effects in fat, brain, muscle, macrophages, and plasma of young mice.
The role of dietary strategies in the modulation of hallmarks of aging.
Markers of aging: Unsupervised integrated analyses of the human plasma proteome.
Revisiting adipose thermogenesis for delaying aging and age-related diseases: Opportunities and challenges.
Gut Microbiota and Its Role in Anti-aging Phenomenon: Evidence-Based Review.
To sleep or not to sleep - Effects on memory in normal aging and disease.
Cut Calories, Lengthen Life Span? Randomized Trial Uncovers Evidence That Calorie Restriction Might Slow Aging, but Questions Remain.
Long-Term Human Spaceflight and Inflammaging: Does it promote aging?
Exploring the role of mitochondria transfer/transplant and their long-non-coding RNAs in regenerative therapies for skin aging.
Mediterranean diet, mental health, cognitive status, quality of life, and successful aging in southern Italian older adults.
Single-nucleus profiling unveils a geroprotective role of the FOXO3 in primate skeletal muscle aging.

Geroscience. 2023 Mar 15.

Four anti-aging drugs and calorie-restricted diet produce parallel effects in fat, brain, muscle, macrophages, and plasma of young mice.

Xinna Li, Madaline McPherson, Mary Hager, Michael Lee, Peter Chang, Richard A Miller.

  Average and maximal lifespan can be increased in mice, in one or both sexes, by four drugs: rapamycin, acarbose, 17a-estradiol, and canagliflozin. We show here that these four drugs, as well as a calorie-restricted diet, can induce a common set of changes in fat, macrophages, plasma, muscle, and brain when evaluated in young adults at 12 months of age. These shared traits include an increase in uncoupling protein UCP1 in brown fat and in subcutaneous and intra-abdominal white fat, a decline in proinflammatory M1 macrophages and corresponding increase in anti-inflammatory M2 macrophages, an increase in muscle fibronectin type III domain containing 5 (FNDC5) and its cleavage product irisin, and higher levels of doublecortin (DCX) and brain-derived neurotrophic factor (BDNF) in brain. Each of these proteins is thought to play a role in one or more age-related diseases, including metabolic, inflammatory, and neurodegenerative diseases. We have previously shown that the same suite of changes is seen in each of four varieties of slow-aging single-gene mutant mice. We propose that these changes may be a part of a shared common pathway that is seen in slow-aging mice whether the delayed aging is due to a mutation, a low-calorie diet, or a drug.

Keywords:  Brain-derived neurotrophic factor (BDNF); Doublecortin (DCX); Fibronectin type III domain containing 5 (FNDC5); Inflammatory; Neurodegenerative; Slow-aging mice; Uncoupling protein UCP1

DOI:  https://doi.org/10.1007/s11357-023-00770-0
Ageing Res Rev. 2023 Mar 09. pii: S1568-1637(23)00067-3. [Epub ahead of print] 101908

The role of dietary strategies in the modulation of hallmarks of aging.

Natasha A Grande de França, Yves Rolland, Sophie Guyonnet, Philipe de Souto Barreto.

  The hallmarks of aging constitute an interconnected network of basic mechanisms that modulate aging and can be modulated by lifestyle factors, including dietary strategies. This narrative review aimed to summarize the evidence on promoting dietary restriction or adherence to specific dietary patterns on cellular hallmarks of aging. Studies with preclinical models or humans were considered. Dietary restriction (DR), usually operationalized as a reduction in caloric intake, is the main strategy applied to study the axis diet-hallmarks of aging. DR has been shown to modulate mainly genomic instability, loss of proteostasis, deregulating nutrient sensing, cellular senescence, and altered intercellular communication. Much less evidence exists on the role of dietary patterns, with most of the studies evaluating the Mediterranean Diet and other similar plant-based diets, and the ketogenic diet. Potential benefits are described in genomic instability, epigenetic alterations, loss of proteostasis, mitochondrial dysfunction, and altered intercellular communication. Given the predominant place of food in human life, it is imperative to determine the impact of nutritional strategies on the modulation of lifespan and health span, considering applicability, long-term adherence, and side effects.

Keywords:  caloric restriction; dietary patterns; fasting; food intake; hallmarks of aging

DOI:  https://doi.org/10.1016/j.arr.2023.101908
Front Aging. 2023 ;4 1112109

Markers of aging: Unsupervised integrated analyses of the human plasma proteome.

L Coenen, B Lehallier, H E de Vries, J Middeldorp.

  Aging associates with an increased susceptibility for disease and decreased quality of life. To date, processes underlying aging are still not well understood, leading to limited interventions with unknown mechanisms to promote healthy aging. Previous research suggests that changes in the blood proteome are reflective of age-associated phenotypes such as frailty. Moreover, experimentally induced changes in the blood proteome composition can accelerate or decelerate underlying aging processes. The aim of this study is to identify a set of proteins in the human plasma associated with aging by integration of the data of four independent, large-scaled datasets using the aptamer-based SomaScan platform on the human aging plasma proteome. Using this approach, we identified a set of 273 plasma proteins significantly associated with aging (aging proteins, APs) across these cohorts consisting of healthy individuals and individuals with comorbidities and highlight their biological functions. We validated the age-associated effects in an independent study using a centenarian population, showing highly concordant effects. Our results suggest that APs are more associated to diseases than other plasma proteins. Plasma levels of APs can predict chronological age, and a reduced selection of 15 APs can still predict individuals' age accurately, highlighting their potential as biomarkers of aging processes. Furthermore, we show that individuals presenting accelerated or decelerated aging based on their plasma proteome, respectively have a more aged or younger systemic environment. These results provide novel insights in the understanding of the aging process and its underlying mechanisms and highlight potential modulators contributing to healthy aging.

Keywords:  SomaScan; aging; blood; disease; health; plasma; proteomics

DOI:  https://doi.org/10.3389/fragi.2023.1112109
Ageing Res Rev. 2023 Mar 15. pii: S1568-1637(23)00071-5. [Epub ahead of print]87 101912

Revisiting adipose thermogenesis for delaying aging and age-related diseases: Opportunities and challenges.

Stefano Tarantini, Madhan Subramanian, Joshua T Butcher, Andriy Yabluchanskiy, Xinna Li, Richard A Miller, Priya Balasubramanian.

  Adipose tissue undergoes significant changes in structure, composition, and function with age including altered adipokine secretion, decreased adipogenesis, altered immune cell profile and increased inflammation. Considering the role of adipose tissue in whole-body energy homeostasis, age-related dysfunction in adipose metabolism could potentially contribute to an increased risk for metabolic diseases and accelerate the onset of other age-related diseases. Increasing cellular energy expenditure in adipose tissue, also referred to as thermogenesis, has emerged as a promising strategy to improve adipose metabolism and treat obesity-related metabolic disorders. However, translating this strategy to the aged population comes with several challenges such as decreased thermogenic response and the paucity of safe pharmacological agents to activate thermogenesis. This mini-review aims to discuss the current body of knowledge on aging and thermogenesis and highlight the unexplored opportunities (cellular mechanisms and secreted factors) to target thermogenic mechanisms for delaying aging and age-related diseases. Finally, we also discuss the emerging role of thermogenic adipocytes in healthspan and lifespan extension.

Keywords:  Adipose metabolism; Aging; Beta-3 adrenergic agonists; Futile metabolic cycling; Healthspan; Thermogenesis; Uncoupling protein 1

DOI:  https://doi.org/10.1016/j.arr.2023.101912
Appl Biochem Biotechnol. 2023 Mar 17.

Gut Microbiota and Its Role in Anti-aging Phenomenon: Evidence-Based Review.

Ruishan Li, Rupak Roy.

  The gut microbiota widely varies from individual to individual, but the variation shows stability over a period of time. The presence of abundant bacterial taxa is a common structure that determines the microbiota of human being. The presence of this microbiota greatly varies from geographic location, sex, food habits and age. Microbiota existing within the gut plays a significant role in nutrient absorption, development of immunity, curing of diseases and various developmental phases. With change in age, chronology diversification and variation of gut microbiota are observed within human being. But it has been observed that with the enhancement of age the richness of the microbial diversity has shown a sharp decline. The enhancement of age also results in the drift of the characteristic of the microbes associated with the microbiota from commensals to pathogenic. Various studies have shown that age associated gut-dysbiosis may result in decrease in tlongevity along with unhealthy aging. The host signalling pathways regulate the presence of the gut microbiota and their longevity. The presence of various nutrients regulates the presence of various microbial species. Innate immunity can be triggered due to the mechanism of gut dysbiosis resulting in the development of various age-related pathological syndromes and early aging. The gut microbiota possesses the ability to communicate with the host system with the help of various types of biomolecules, epigenetic mechanisms and various types of signalling-independent pathways. Drift in this mechanism of communication may affect the life span along with the health of the host. Thus, this review would focus on the use of gut-microbiota in anti-aging and healthy conditions of the host system.

Keywords:  Anti-aging; Cell-to-cell communication; Microbes; Microbiota

DOI:  https://doi.org/10.1007/s12010-023-04423-y
Aging Brain. 2023 ;3 100068

To sleep or not to sleep - Effects on memory in normal aging and disease.

Daniel Kroeger, Ramalingam Vetrivelan.

  Sleep behavior undergoes significant changes across the lifespan, and aging is associated with marked alterations in sleep amounts and quality. The primary sleep changes in healthy older adults include a shift in sleep timing, reduced slow-wave sleep, and impaired sleep maintenance. However, neurodegenerative and psychiatric disorders are more common among the elderly, which further worsen their sleep health. Irrespective of the cause, insufficient sleep adversely affects various bodily functions including energy metabolism, mood, and cognition. In this review, we will focus on the cognitive changes associated with inadequate sleep during normal aging and the underlying neural mechanisms.

Keywords:  Alzheimer's disease; Glymphatic system; Hypothalamus; Sleep-wake circuits; Slow-wave oscillations

DOI:  https://doi.org/10.1016/j.nbas.2023.100068
JAMA. 2023 Mar 15.

Cut Calories, Lengthen Life Span? Randomized Trial Uncovers Evidence That Calorie Restriction Might Slow Aging, but Questions Remain.

Rita Rubin.

DOI: https://doi.org/10.1001/jama.2023.2437
Ageing Res Rev. 2023 Mar 12. pii: S1568-1637(23)00068-5. [Epub ahead of print] 101909

Long-Term Human Spaceflight and Inflammaging: Does it promote aging?

Miriam Capri, Maria Conte, Erika Ciurca, Chiara Pirazzini, Paolo Garagnani, Aurelia Santoro, Federica Longo, Stefano Salvioli, Patrick Lau, Ralf Moeller, Jens Jordan, Thomas Illig, Maria-Moreno Villanueva, Markus Gruber, Alexander Bürkle, Claudio Franceschi, Jörn Rittweger.

  Spaceflight and its associated stressors, such as microgravity, radiation exposure, confinement, circadian derailment and disruptive workloads represent an unprecedented type of exposome that is entirely novel from an evolutionary stand point. Within this perspective, we aimed to review the effects of prolonged spaceflight on immune-neuroendocrine systems, brain and brain-gut axis, cardiovascular system and musculoskeletal apparatus, highlighting in particular the similarities with an accelerated aging process. In particular, spaceflight-induced muscle atrophy/sarcopenia and bone loss, vascular and metabolic changes, hyper and hypo reaction of innate and adaptive immune system appear to be modifications shared with the aging process. Most of these modifications are mediated by molecular events that include oxidative and mitochondrial stress, autophagy, DNA damage repair and telomere length alteration, among others, which directly or indirectly converge on the activation of an inflammatory response. According to the inflammaging theory of aging, such an inflammatory response could be a driver of an acceleration of the normal, physiological rate of aging and it is likely that all the systemic modifications in turn lead to an increase of inflammaging in a sort of vicious cycle. The most updated countermeasures to fight these modifications will be also discussed in the light of their possible application not only for astronauts' benefit, but also for older adults on the ground.

Keywords:  NF- κB; aging; exposome; human spaceflight; inflammaging

DOI:  https://doi.org/10.1016/j.arr.2023.101909
Mitochondrion. 2023 Mar 13. pii: S1567-7249(23)00029-6. [Epub ahead of print]

Exploring the role of mitochondria transfer/transplant and their long-non-coding RNAs in regenerative therapies for skin aging.

Sebastian Peñaherrera, Cristina Ruiz, Verónica Castañeda, Kathryn Livingston, Diego Barba, Verónica A Burzio, Andrés Caicedo, Keshav K Singh.

  Advancing age and environmental stressors lead to mitochondrial dysfunction in the skin, inducing premature aging, impaired regeneration, and greater risk of cancer. Cells rely on the communication between the mitochondria and the nucleus by tight regulation of long non-coding RNAs (lncRNAs) to avoid premature aging and maintain healthy skin. LncRNAs act as key regulators of cell proliferation, differentiation, survival, and maintenance of skin structure. However, research on how the lncRNAs are dysregulated during aging and due to stressors is needed to develop therapies to regenerate skin's function and structure. In this article, we discuss how age and environmental stressors may alter lncRNA homeodynamics, compromising cell survival and skin health, and how these factors may become inducers of skin aging. We describe skin cell types and how they depend on mitochondrial function and lncRNAs. We also provide a list of mitochondria localized and nuclear lncRNAs that can serve to better understand skin aging. Using bioinformatic prediction tools, we predict possible functions of lncRNAs based on their subcellular localization. We also search for experimentally determined protein interactions and the biological processes involved. Finally, we provide therapeutic strategies based on gene editing and mitochondria transfer/transplant (AMT/T) to restore lncRNA regulation and skin health. This article offers a unique perspective in understanding and defining the therapeutic potential of mitochondria localized lncRNAs (mt-lncRNAs) produced and AMT/T to treat skin aging and related diseases.

Keywords:  AMT/T; Skin; aging; artificial mitochondrial transfer / transplant; gene editing; lncRNAs; mitochondria

DOI:  https://doi.org/10.1016/j.mito.2023.02.012
Exp Gerontol. 2023 Mar 10. pii: S0531-5565(23)00064-5. [Epub ahead of print] 112143

Mediterranean diet, mental health, cognitive status, quality of life, and successful aging in southern Italian older adults.

Justyna Godos, Giuseppe Grosso, Raffaele Ferri, Filippo Caraci, Giuseppe Lanza, Wahidah H Al-Qahtani, Giuseppe Caruso, Sabrina Castellano.

  Healthy successful aging with preserved mental and cognitive health is expected to be one of the most important challenges of the growing old population globally. Studies investigating these multi-dimensional aspects of senescence are important to identify potential targets for early prevention. The aim of this study was to investigate the relation between adherence to the Mediterranean diet and mental and cognitive health, quality of life, and successful aging in middle-age and older adults living in Sicily, southern Italy. Data from a sample of 883 individuals was collected including information on food intake (through a 110-item food frequency questionnaire), sleep quality (through the Pittsburgh sleep quality index) depressive symptoms (through the Center for the Epidemiological Studies of Depression Short Form), quality of life (through the Manchester Short Assessment of Quality of Life), cognitive status (through the Short Portable Mental Status Questionnaire), and overall successful aging (through the Successful Aging Index). Multivariate logistic regression analyses were conducted to assess the association between adherence to the Mediterranean diet and the outcomes investigated. After adjustment for potential confounding factors, individuals in the highest quartile of adherence to the Mediterranean diet were less likely to have cognitive impairment (OR = 0.19, 95 % CI: 0.04, 0.86), depressive symptoms (OR = 0.19, 95 % CI: 0.08, 0.46) and more likely to have good quality of life (OR = 14.04, 95 % CI: 6.81, 28.93); significant results were also found for individuals in the third quartile of Mediterranean diet adherence and good sleep quality (OR = 1.65, 95 % CI: 1.03, 2.64). Moreover, individuals in the highest quartile of adherence were more likely to have a successful aging (OR = 1.65, 95 % CI: 1.01, 2.68). In conclusion, this study supports the hypothesis that adherence to the Mediterranean diet provides a positive trajectory toward a healthy successful aging, with major potential benefits toward mental and cognitive health.

Keywords:  Cognitive status; Depressive symptoms; Mediterranean diet; Quality of life; Sleep quality; Successful aging

DOI:  https://doi.org/10.1016/j.exger.2023.112143
Protein Cell. 2022 Nov 22. pii: pwac061. [Epub ahead of print]

Single-nucleus profiling unveils a geroprotective role of the FOXO3 in primate skeletal muscle aging.

Ying Jing, Yuesheng Zuo, Yang Yu, Liang Sun, Zhengrong Yu, Shuai Ma, Qian Zhao, Guoqiang Sun, Huifang Hu, Jingyi Li, Daoyuan Huang, Lixiao Liu, Jiaming Li, Zijuan Xin, Haoyan Huang, Juan Carlos Izpisua Belmonte, Weiqi Zhang, Si Wang, Jing Qu, Guang-Hui Liu.

  Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.

Keywords:  FOXO3; aging; primate; single-nucleus RNA sequencing; skeletal muscle

DOI:  https://doi.org/10.1093/procel/pwac061