Aging, Lifespan & Longevity

Somatic deficiency causes reproductive parasitism in a fungus.

Nat Commun. 2021 02 04;12(1):783

Authors: Grum-Grzhimaylo AA, Bastiaans E, van den Heuvel J, Berenguer Millanes C, Debets AJM, Aanen DK

Abstract
Some multicellular organisms can fuse because mergers potentially provide mutual benefits. However, experimental evolution in the fungus Neurospora crassa has demonstrated that free fusion of mycelia favours cheater lineages, but the mechanism and evolutionary dynamics of this exploitation are unknown. Here we show, paradoxically, that all convergently evolved cheater lineages have similar fusion deficiencies. These mutants are unable to initiate fusion but retain access to wild-type mycelia that fuse with them. This asymmetry reduces cheater-mutant contributions to somatic substrate-bound hyphal networks, but increases representation of their nuclei in the aerial reproductive hyphae. Cheaters only benefit when relatively rare and likely impose genetic load reminiscent of germline senescence. We show that the consequences of somatic fusion can be unequally distributed among fusion partners, with the passive non-fusing partner profiting more. We discuss how our findings may relate to the extensive variation in fusion frequency of fungi found in nature.

PMID: 33542245 [PubMed - indexed for MEDLINE]

Cell-density independent increased lymphocyte production and loss rates post-autologous HSCT.

Elife. 2021 Feb 04;10:

Authors: Baliu Piqué M, van Hoeven V, Drylewicz J, van der Wagen LE, Janssen A, Otto SA, van Zelm MC, de Boer RJ, Kuball JJ, Borghans JA, Tesselaar K

Abstract
Lymphocyte numbers need to be quite tightly regulated. It is generally assumed that lymphocyte production and lifespan increase homeostatically when lymphocyte numbers are low, and vice versa return to normal once cell numbers have normalized. This widely-accepted concept is largely based on experiments in mice, but is hardly investigated in vivo in humans. Here we quantified lymphocyte production and loss rates in vivo in patients 0.5-1 year after their autologous hematopoietic stem cell transplantation (autoHSCT). We indeed found that the production rates of most T-cell and B-cell subsets in autoHSCT-patients were 2 to 8-times higher than in healthy controls, but went hand in hand with a 3 to 9-fold increase in cell loss rates. Both rates also did not normalize when cell numbers did. This shows that increased lymphocyte production and loss rates occur even long after autoHSCT and can persist in the face of apparently normal cell numbers.

PMID: 33538246 [PubMed - as supplied by publisher]

ATF3 drives senescence by reconstructing accessible chromatin profiles.

Aging Cell. 2021 Feb 04;:e13315

Authors: Zhang C, Zhang X, Huang L, Guan Y, Huang X, Tian XL, Zhang L, Tao W

Abstract
Chromatin organization and transcriptional profiles undergo tremendous reordering during senescence. However, uncovering the regulatory mechanisms between chromatin reconstruction and gene expression in senescence has been elusive. Here, we depicted the landscapes of both chromatin accessibility and gene expression to reveal gene regulatory networks in human umbilical vein endothelial cell (HUVEC) senescence and found that chromatin accessibilities are redistributed during senescence. Particularly, the intergenic chromatin was massively shifted with the increased accessibility regions (IARs) or decreased accessibility regions (DARs), which were mainly enhancer elements. We defined AP-1 transcription factor family as being responsible for driving chromatin accessibility reconstruction in IARs, where low DNA methylation improved binding affinity of AP-1 and further increased the chromatin accessibility. Among AP-1 transcription factors, we confirmed ATF3 was critical to reconstruct chromatin accessibility to promote cellular senescence. Our results described a dynamic landscape of chromatin accessibility whose remodeling contributes to the senescence program, we identified that AP-1 was capable of reorganizing the chromatin accessibility profile to regulate senescence.

PMID: 33539668 [PubMed - as supplied by publisher]

Deterioration of Nuclear morphology and architecture: A hallmark of senescence and aging.

Ageing Res Rev. 2021 Feb 01;:101264

Authors: Pathak RU, Soujanya M, Mishra RK

Abstract
The metazoan nucleus is a highly structured organelle containing several well-defined sub-organelles. It is the largest organelle inside a cell taking up from one tenth to half of entire cell volume. This makes it one of the easiest organelles to identify and study under the microscope. Abnormalities in the nuclear morphology and architecture are commonly observed in an aged and senescent cell. For example, the nuclei enlarge, loose their shape, appear lobulated, harbour nuclear membrane invaginations, carry enlarged/fragmented nucleolus, loose heterochromatin, etc. In this review we discuss about the age-related changes in nuclear features and elaborate upon the molecular reasons driving the change. Many of these changes can be easily imaged under a microscope and analysed in silico. Thus, computational image analysis of nuclear features appears to be a promising tool to evaluate physiological age of a cell and offers to be a legitimate biomarker. It can be used to examine progression of age-related diseases and evaluate therapies.

PMID: 33540043 [PubMed - as supplied by publisher]

Mitohormesis in Hypothalamic POMC Neurons Mediates Regular Exercise-Induced High-Turnover Metabolism.

Cell Metab. 2021 Feb 02;33(2):334-349.e6

Authors: Kang GM, Min SH, Lee CH, Kim JY, Lim HS, Choi MJ, Jung SB, Park JW, Kim S, Park CB, Dugu H, Choi JH, Jang WH, Park SE, Cho YM, Kim JG, Kim KG, Choi CS, Kim YB, Lee C, Shong M, Kim MS

Abstract
Low-grade mitochondrial stress can promote health and longevity, a phenomenon termed mitohormesis. Here, we demonstrate the opposing metabolic effects of low-level and high-level mitochondrial ribosomal (mitoribosomal) stress in hypothalamic proopiomelanocortin (POMC) neurons. POMC neuron-specific severe mitoribosomal stress due to Crif1 homodeficiency causes obesity in mice. By contrast, mild mitoribosomal stress caused by Crif1 heterodeficiency in POMC neurons leads to high-turnover metabolism and resistance to obesity. These metabolic benefits are mediated by enhanced thermogenesis and mitochondrial unfolded protein responses (UPRmt) in distal adipose tissues. In POMC neurons, partial Crif1 deficiency increases the expression of β-endorphin (β-END) and mitochondrial DNA-encoded peptide MOTS-c. Central administration of MOTS-c or β-END recapitulates the adipose phenotype of Crif1 heterodeficient mice, suggesting these factors as potential mediators. Consistently, regular running exercise at moderate intensity stimulates hypothalamic MOTS-c/β-END expression and induces adipose tissue UPRmt and thermogenesis. Our findings indicate that POMC neuronal mitohormesis may underlie exercise-induced high-turnover metabolism.

PMID: 33535098 [PubMed - as supplied by publisher]

Translational Control during Cellular Senescence.

Mol Cell Biol. 2021 01 25;41(2):

Authors: Payea MJ, Anerillas C, Tharakan R, Gorospe M

Abstract
Senescence is a state of long-term cell cycle arrest that arises in cells that have incurred sublethal damage. While senescent cells no longer replicate, they remain metabolically active and further develop unique and stable phenotypes that are not present in proliferating cells. On one hand, senescent cells increase in size, maintain an active mTORC1 complex, and produce and secrete a substantial amount of inflammatory proteins as part of the senescence-associated secretory phenotype (SASP). On the other hand, these progrowth phenotypes contrast with the p53-mediated growth arrest typical of senescent cells that is associated with nucleolar stress and an inhibition of rRNA processing and ribosome biogenesis. In sum, translation in senescent cells paradoxically comprises both a global repression of translation triggered by DNA damage and a select increase in the translation of specific proteins, including SASP factors.

PMID: 33077499 [PubMed - indexed for MEDLINE]

A small-molecule ICMT inhibitor delays senescence of Hutchinson-Gilford progeria syndrome cells.

Elife. 2021 Feb 02;10:

Authors: Chen X, Yao H, Kashif M, Revêchona G, Eriksson M, Hu J, Wang T, Liu Y, Tüksammel E, Strömblad S, Ahearn IM, Philips MR, Wiel C, Ibrahim MX, Bergo MO

Abstract
A farnesylated and methylated form of prelamin A called progerin causes Hutchinson-Gilford progeria syndrome (HGPS). Inhibiting progerin methylation by inactivating the isoprenylcysteine carboxylmethyltransferase (ICMT) gene stimulates proliferation of HGPS cells and improves survival of Zmpste24-deficient mice. However, we don't know whether Icmt inactivation improves phenotypes in an authentic HGPS mouse model. Moreover, it is unknown whether pharmacologic targeting of ICMT would be tolerated by cells and produce similar cellular effects as genetic inactivation. Here, we show that knockout of Icmt improves survival of HGPS mice and restores vascular smooth muscle cell numbers in the aorta. We also synthesized a potent ICMT inhibitor called C75 and found that it delays senescence and stimulates proliferation of late-passage HGPS cells and Zmpste24-deficient mouse fibroblasts. Importantly, C75 did not influence proliferation of wild-type human cells or Zmpste24-deficient mouse cells lacking Icmt, indicating drug specificity. These results raise hopes that ICMT inhibitors could be useful for treating children with HGPS.

PMID: 33526168 [PubMed - in process]

Gross ways to live long: Parasitic worms as an anti-inflammaging therapy?

Elife. 2021 Feb 02;10:

Authors: Zhang B, Gems D

Abstract
Evolutionary medicine argues that disease can arise because modern conditions do not match those in which we evolved. For example, a decline in exposure to commensal microbes and gastrointestinal helminths in developed countries has been linked to increased prevalence of allergic and autoimmune inflammatory disorders (the hygiene hypothesis). Accordingly, probiotic therapies that restore 'old friend' microbes and helminths have been explored as Darwinian treatments for these disorders. A further possibility is that loss of old friend commensals also increases the sterile, aging-associated inflammation known as inflammaging, which contributes to a range of age-related diseases, including cardiovascular disease, dementia, and cancer. Interestingly, Crowe et al., 2020 recently reported that treatment with a secreted glycoprotein from a parasitic nematode can protect against murine aging by induction of anti-inflammatory mechanisms. Here, we explore the hypothesis that restorative helminth therapy would have anti-inflammaging effects. Could worm infections provide broad-spectrum protection against age-related disease?

PMID: 33526169 [PubMed - in process]

Cell of all trades: oligodendrocyte precursor cells in synaptic, vascular, and immune function.

Genes Dev. 2021 Feb 01;35(3-4):180-198

Authors: Akay LA, Effenberger AH, Tsai LH

Abstract
Oligodendrocyte precursor cells (OPCs) are not merely a transitory progenitor cell type, but rather a distinct and heterogeneous population of glia with various functions in the developing and adult central nervous system. In this review, we discuss the fate and function of OPCs in the brain beyond their contribution to myelination. OPCs are electrically sensitive, form synapses with neurons, support blood-brain barrier integrity, and mediate neuroinflammation. We explore how sex and age may influence OPC activity, and we review how OPC dysfunction may play a primary role in numerous neurological and neuropsychiatric diseases. Finally, we highlight areas of future research.

PMID: 33526585 [PubMed - in process]

Asymmetric thinning of the cerebral cortex across the adult lifespan is accelerated in Alzheimer's disease.

Nat Commun. 2021 02 01;12(1):721

Authors: Roe JM, Vidal-Piñeiro D, Sørensen Ø, Brandmaier AM, Düzel S, Gonzalez HA, Kievit RA, Knights E, Kühn S, Lindenberger U, Mowinckel AM, Nyberg L, Park DC, Pudas S, Rundle MM, Walhovd KB, Fjell AM, Westerhausen R, Australian Imaging Biomarkers and Lifestyle Flagship Study of Ageing

Abstract
Aging and Alzheimer's disease (AD) are associated with progressive brain disorganization. Although structural asymmetry is an organizing feature of the cerebral cortex it is unknown whether continuous age- and AD-related cortical degradation alters cortical asymmetry. Here, in multiple longitudinal adult lifespan cohorts we show that higher-order cortical regions exhibiting pronounced asymmetry at age ~20 also show progressive asymmetry-loss across the adult lifespan. Hence, accelerated thinning of the (previously) thicker homotopic hemisphere is a feature of aging. This organizational principle showed high consistency across cohorts in the Lifebrain consortium, and both the topological patterns and temporal dynamics of asymmetry-loss were markedly similar across replicating samples. Asymmetry-change was further accelerated in AD. Results suggest a system-wide dedifferentiation of the adaptive asymmetric organization of heteromodal cortex in aging and AD.

PMID: 33526780 [PubMed - indexed for MEDLINE]

Calcium channel ITPR2 and mitochondria-ER contacts promote cellular senescence and aging.

Nat Commun. 2021 02 01;12(1):720

Authors: Ziegler DV, Vindrieux D, Goehrig D, Jaber S, Collin G, Griveau A, Wiel C, Bendridi N, Djebali S, Farfariello V, Prevarskaya N, Payen L, Marvel J, Aubert S, Flaman JM, Rieusset J, Martin N, Bernard D

Abstract
Cellular senescence is induced by stresses and results in a stable proliferation arrest accompanied by a pro-inflammatory secretome. Senescent cells accumulate during aging, promoting various age-related pathologies and limiting lifespan. The endoplasmic reticulum (ER) inositol 1,4,5-trisphosphate receptor, type 2 (ITPR2) calcium-release channel and calcium fluxes from the ER to the mitochondria are drivers of senescence in human cells. Here we show that Itpr2 knockout (KO) mice display improved aging such as increased lifespan, a better response to metabolic stress, less immunosenescence, as well as less liver steatosis and fibrosis. Cellular senescence, which is known to promote these alterations, is decreased in Itpr2 KO mice and Itpr2 KO embryo-derived cells. Interestingly, ablation of ITPR2 in vivo and in vitro decreases the number of contacts between the mitochondria and the ER and their forced contacts induce premature senescence. These findings shed light on the role of contacts and facilitated exchanges between the ER and the mitochondria through ITPR2 in regulating senescence and aging.

PMID: 33526781 [PubMed - indexed for MEDLINE]

Novel DNA methylation marker discovery by assumption-free genome-wide association analysis of cognitive function in twins.

Aging Cell. 2021 Feb 02;:e13293

Authors: Mohammadnejad A, Soerensen M, Baumbach J, Mengel-From J, Li W, Lund J, Li S, Christiansen L, Christensen K, Hjelmborg JVB, Tan Q

Abstract
Privileged by rapid increase in available epigenomic data, epigenome-wide association studies (EWAS) are to make a profound contribution to understand the molecular mechanism of DNA methylation in cognitive aging. Current statistical methods used in EWAS are dominated by models based on multiple assumptions, for example, linear relationship between molecular profiles and phenotype, normal distribution for the methylation data and phenotype. In this study, we applied an assumption-free method, the generalized correlation coefficient (GCC), and compare it to linear models, namely the linear mixed model and kinship model. We use DNA methylation associated with a cognitive score in 400 and 206 twins as discovery and replication samples respectively. DNA methylation associated with cognitive function using GCC, linear mixed model, and kinship model, identified 65 CpGs (p < 1e-04) from discovery sample displaying both nonlinear and linear correlations. Replication analysis successfully replicated 9 of these top CpGs. When combining results of GCC and linear models to cover diverse patterns of relationships, we identified genes like KLHDC4, PAPSS2, and MRPS18B as well as pathways including focal adhesion, axon guidance, and some neurological signaling. Genomic region-based analysis found 15 methylated regions harboring 11 genes, with three verified in gene expression analysis, also the 11 genes were related to top functional clusters including neurohypophyseal hormone and maternal aggressive behaviors. The GCC approach detects valuable methylation sites missed by traditional linear models. A combination of methylation markers from GCC and linear models enriched biological pathways sensible in neurological function that could implicate cognitive performance and cognitive aging.

PMID: 33528912 [PubMed - as supplied by publisher]

STAB: a spatio-temporal cell atlas of the human brain.

Nucleic Acids Res. 2021 01 08;49(D1):D1029-D1037

Authors: Song L, Pan S, Zhang Z, Jia L, Chen WH, Zhao XM

Abstract
The human brain is the most complex organ consisting of billions of neuronal and non-neuronal cells that are organized into distinct anatomical and functional regions. Elucidating the cellular and transcriptome architecture underlying the brain is crucial for understanding brain functions and brain disorders. Thanks to the single-cell RNA sequencing technologies, it is becoming possible to dissect the cellular compositions of the brain. Although great effort has been made to explore the transcriptome architecture of the human brain, a comprehensive database with dynamic cellular compositions and molecular characteristics of the human brain during the lifespan is still not available. Here, we present STAB (a Spatio-Temporal cell Atlas of the human Brain), a database consists of single-cell transcriptomes across multiple brain regions and developmental periods. Right now, STAB contains single-cell gene expression profiling of 42 cell subtypes across 20 brain regions and 11 developmental periods. With STAB, the landscape of cell types and their regional heterogeneity and temporal dynamics across the human brain can be clearly seen, which can help to understand both the development of the normal human brain and the etiology of neuropsychiatric disorders. STAB is available at http://stab.comp-sysbio.org.

PMID: 32976581 [PubMed - indexed for MEDLINE]

Hydrogen sulfide in longevity and pathologies: inconsistency is malodorous.

Ageing Res Rev. 2021 Jan 28;:101262

Authors: Sokolov AS, Nekrasov PV, Shaposhnikov MV, Moskalev AA

Abstract
Hydrogen sulfide (H2S) is one of the biologically active gases (gasotransmitters), which plays an important role in various physiological processes and aging. Its production in the course of methionine and cysteine catabolism and its degradation are finely balanced, and impairment of H2S homeostasis is associated with various pathologies. Despite the strong geroprotective action of exogenous H2S in C. elegans, there are controversial effects of hydrogen sulfide and its donors on longevity in other models, as well as on stress resistance, age-related pathologies and aging processes, including regulation of senescence-associated secretory phenotype (SASP) and senescent cell anti-apoptotic pathways (SCAPs). Here we discuss that the translation potential of H2S as a geroprotective compound is influenced by a multiplicity of its molecular targets, pleiotropic biological effects, and the overlapping ranges of toxic and beneficial doses. We also consider the challenges of the targeted delivery of H2S at the required dose. Along with this, the complexity of determining the natural levels of H2S in animal and human organs and their ambiguous correlations with longevity are reviewed.

PMID: 33516916 [PubMed - as supplied by publisher]

Global, cell non-autonomous gene regulation drives individual lifespan among isogenic C. elegans.

Elife. 2021 Feb 01;10:

Authors: Kinser HE, Mosley MC, Plutzer IB, Pincus Z

Abstract
Across species, lifespan is highly variable among individuals within a population. Even genetically identical C. elegans reared in homogeneous environments are as variable in lifespan as outbred human populations. We hypothesized that persistent inter-individual differences in expression of key regulatory genes drives this lifespan variability. As a test, we examined the relationship between future lifespan and the expression of 22 microRNA promoter::GFP constructs. Surprisingly, expression of nearly half of these reporters, well before death, could effectively predict lifespan. This indicates that prospectively long- vs. short-lived individuals have highly divergent patterns of transgene expression and transcriptional regulation. The gene-regulatory processes reported on by two of the most lifespan-predictive transgenes do not require DAF-16, the FOXO transcription factor that is a principal effector of insulin/insulin-like growth factor (IGF-1) signaling. Last, we demonstrate a hierarchy of redundancy in lifespan-predictive ability among three transgenes expressed in distinct tissues, suggesting that they collectively report on an organism-wide, cell non-autonomous process that acts to set each individual's lifespan.

PMID: 33522488 [PubMed - as supplied by publisher]

Decreased p53 is associated with a decline in asymmetric stem cell self-renewal in aged human epidermis.

Aging Cell. 2021 Feb 01;:e13310

Authors: Charruyer A, Weisenberger T, Li H, Khalifa A, Schroeder AW, Belzer A, Ghadially R

Abstract
With age, the epidermis becomes hypoplastic and hypoproliferative. Hypoproliferation due to aging has been associated with decreased stem cell (SC) self-renewal in multiple murine tissues. The fate of SC self-renewal divisions can be asymmetric (one SC, one committed progenitor) or symmetric (two SCs). Increased asymmetric SC self-renewal has been observed in inflammatory-mediated hyperproliferation, while increased symmetric SC self-renewal has been observed in cancers. We analyzed SC self-renewal divisions in aging human epidermis to better understand the role of SCs in the hypoproliferation of aging. In human subjects, neonatal to 78 years, there was an age-dependent decrease in epidermal basal layer divisions. The balance of SC self-renewal shifted toward symmetric SC self-renewal, with a decline in asymmetric SC self-renewal. Asymmetric SC divisions maintain epidermal stratification, and this decrease may contribute to the hypoplasia of aging skin. P53 decreases in multiple tissues with age, and p53 has been shown to promote asymmetric SC self-renewal. Fewer aged than adult ALDH+CD44+ keratinocyte SCs exhibited p53 expression and activity and Nutlin-3 (a p53 activator) returned p53 activity as well as asymmetric SC self-renewal divisions to adult levels. Nutlin-3 increased Notch signaling (NICD, Hes1) and DAPT inhibition of Notch activation prevented Nutlin-3 (p53)-induced asymmetric SC self-renewal divisions in aged keratinocytes. These studies indicate a role for p53 in the decreased asymmetric SC divisions with age and suggest that in aged keratinocytes, Notch is required for p53-induced asymmetric SC divisions.

PMID: 33524216 [PubMed - as supplied by publisher]

Metformin inhibits chronic kidney disease-induced DNA damage and senescence of mesenchymal stem cells.

Aging Cell. 2021 Feb 01;:e13317

Authors: Kim H, Yu MR, Lee H, Kwon SH, Jeon JS, Han DC, Noh H

Abstract
Mesenchymal stem cells (MSCs) are promising source of cell-based regenerative therapy. In consideration of the risk of allosensitization, autologous MSC-based therapy is preferred over allogenic transplantation in patients with chronic kidney disease (CKD). However, it remains uncertain whether adequate cell functionality is maintained under uremic conditions. As chronic inflammation and oxidative stress in CKD may lead to the accumulation of senescent cells, we investigated cellular senescence of CKD MSCs and determined the effects of metformin on CKD-associated cellular senescence in bone marrow MSCs from sham-operated and subtotal nephrectomized mice and further explored in adipose tissue-derived MSCs from healthy kidney donors and patients with CKD. CKD MSCs showed reduced proliferation, accelerated senescence, and increased DNA damage as compared to control MSCs. These changes were significantly attenuated following metformin treatment. Lipopolysaccharide and transforming growth factor β1-treated HK2 cells showed lower tubular expression of proinflammatory and fibrogenesis markers upon co-culture with metformin-treated CKD MSCs than with untreated CKD MSCs, suggestive of enhanced paracrine action of CKD MSCs mediated by metformin. In unilateral ureteral obstruction kidneys, metformin-treated CKD MSCs more effectively attenuated inflammation and fibrosis as compared to untreated CKD MSCs. Thus, metformin preconditioning may exhibit a therapeutic benefit by targeting accelerated senescence of CKD MSCs.

PMID: 33524231 [PubMed - as supplied by publisher]

Hallmarks and detection techniques of cellular senescence and cellular ageing in immune cells.

Aging Cell. 2021 02;20(2):e13316

Authors: Zhou D, Borsa M, Simon AK

Abstract
The ageing of the global population brings about unprecedented challenges. Chronic age-related diseases in an increasing number of people represent an enormous burden for health and social care. The immune system deteriorates during ageing and contributes to many of these age-associated diseases due to its pivotal role in pathogen clearance, tissue homeostasis and maintenance. Moreover, in order to develop treatments for COVID-19, we urgently need to acquire more knowledge about the aged immune system, as older adults are disproportionally and more severely affected. Changes with age lead to impaired responses to infections, malignancies and vaccination, and are accompanied by chronic, low-degree inflammation, which together is termed immunosenescence. However, the molecular and cellular mechanisms that underlie immunosenescence, termed immune cell senescence, are mostly unknown. Cellular senescence, characterised by an irreversible cell cycle arrest, is thought to be the cause of tissue and organismal ageing. Thus, better understanding of cellular senescence in immune populations at single-cell level may provide us with insight into how immune cell senescence develops over the life time of an individual. In this review, we will briefly introduce the phenotypic characterisation of aged innate and adaptive immune cells, which also contributes to overall immunosenescence, including subsets and function. Next, we will focus on the different hallmarks of cellular senescence and cellular ageing, and the detection techniques most suitable for immune cells. Applying these techniques will deepen our understanding of immune cell senescence and to discover potential druggable pathways, which can be modulated to reverse immune ageing.

PMID: 33524238 [PubMed - indexed for MEDLINE]

Perspectives on skeletal muscle stem cells.

Nat Commun. 2021 01 29;12(1):692

Authors: Relaix F, Bencze M, Borok MJ, Der Vartanian A, Gattazzo F, Mademtzoglou D, Perez-Diaz S, Prola A, Reyes-Fernandez PC, Rotini A, Taglietti

Abstract
Skeletal muscle has remarkable regeneration capabilities, mainly due to its resident muscle stem cells (MuSCs). In this review, we introduce recently developed technologies and the mechanistic insights they provide to the understanding of MuSC biology, including the re-definition of quiescence and Galert states. Additionally, we present recent studies that link MuSC function with cellular heterogeneity, highlighting the complex regulation of self-renewal in regeneration, muscle disorders and aging. Finally, we discuss MuSC metabolism and its role, as well as the multifaceted regulation of MuSCs by their niche. The presented conceptual advances in the MuSC field impact on our general understanding of stem cells and their therapeutic use in regenerative medicine.

PMID: 33514709 [PubMed - indexed for MEDLINE]

Aging Adipose: Depot Location Dictates Age-Associated Expansion and Dysfunction.

Ageing Res Rev. 2021 Jan 27;:101259

Authors: Von Bank H, Kirsh C, Simcox J

Abstract
Adipose tissue has a variety of diverse functions that maintain energy homeostasis. In conditions of excess energy availability, adipose tissue increases its lipid storage and communicates the nutritional abundance to various organs in the body. In conditions of energy depletion, such as fasting, cold exposure, or prolonged exercise, triglycerides stored in adipose tissue are released as free fatty acids to support the shift to catabolic metabolism. These diverse functions of storage, communication, and energy homeostasis are shared between numerous adipose depots including subcutaneous, visceral, brown, beige, intramuscular, marrow, and dermal adipose tissue. As organisms age, the cellular composition of these depots shifts to facilitate increased inflammatory cell infiltration, decreased vasculature, and increased adipocyte quantity and lipid droplet size. The purpose of this review is to give a comprehensive overview of the molecular and cellular changes that occur in various aged adipose depots and discuss their impact on physiology. The molecular signature of aged adipose leads to higher prevalence of metabolic disease in aged populations including type 2 diabetes, cardiovascular disease, Alzheimer's disease, and certain types of cancer.

PMID: 33515751 [PubMed - as supplied by publisher]