Onset Of Age-related Diseases Research Articles

High-dimensional Ageome Representations of Biological Aging across Functional Modules.

The aging process involves numerous molecular changes that lead to functional decline and increased disease and mortality risk. While epigenetic aging clocks have shown accuracy in predicting biological age, they typically provide single estimates for the samples and lack mechanistic insights. In this study, we challenge the paradigm that aging can be sufficiently described with a single biological age estimate. We describe Ageome, a computational framework for measuring the epigenetic age of thousands of molecular pathways simultaneously in mice and humans. Ageome is based on the premise that an organism's overall biological age can be approximated by the collective ages of its functional modules, which may age at different rates and have different biological ages. We show that, unlike conventional clocks, Ageome provides a high-dimensional representation of biological aging across cellular functions, enabling comprehensive assessment of aging dynamics within an individual, in a population, and across species. Application of Ageome to longevity intervention models revealed distinct patterns of pathway-specific age deceleration. Notably, cell reprogramming, while rejuvenating cells, also accelerated aging of some functional modules. When applied to human cohorts, Ageome demonstrated heterogeneity in predictive power for mortality risk, and some modules showed better performance in predicting the onset of age-related diseases, especially cancer, compared to existing clocks. Together, the Ageome framework offers a comprehensive and interpretable approach for assessing aging, providing insights into mechanisms and targets for intervention.

Selective autophagy: a therapeutic target for healthy aging?

At the molecular level, aging is characterized by the accumulation of unresolved damage to essential components of cells, such as DNA, proteins, and organelles, which over time contributes to cellular malfunction and the onset of age-associated diseases. To counteract this detrimental process, cells are equipped with protective mechanisms that prevent or reverse molecular damage. Arguably, the cellular recycling process of autophagy is one of the most versatile repair pathways that cells display. Autophagy allows the degradation and recycling of surplus and/or damaged cytosolic components, which otherwise may pose a threat to cellular homeostasis. This is achieved via the delivery of cytoplasmic components to lysosomes, which are organelles equipped with a sophisticated set of degradative enzymes that eliminate cellular waste and transform it into building blocks to maintain cellular function. There are different autophagic routes, known as macroautophagy, microautophagy, and chaperone-mediated autophagy, via which a variety of cellular components, ranging from organelles, DNA, proteins, and lipids, can be delivered to lysosomes for proper turnover. While these autophagy pathways operate to maintain cellular homeostasis over time, an overall deficit in autophagic function leads to aging acceleration and is correlated with the onset of age-related diseases. However, the extent to which specific autophagic pathways and the selective degradation of cellular components contribute to aging, as well as the molecular interplay among the different routes, remain elusive and constitute a main research direction. This narrative review summarizes the implications of autophagy subtypes in aging, focusing on the contributions of each pathway to select cargo degradation and their interaction, and highlights future lines of research toward identifying potential therapeutic routes for the amelioration of selective autophagy to promote healthy aging.

Curcumin Inhibits TORC1 and Prolongs the Lifespan of Cells with Mitochondrial Dysfunction.

Aging is an inevitable biological process that contributes to the onset of age-related diseases, often as a result of mitochondrial dysfunction. Understanding the mechanisms behind aging is crucial for developing therapeutic interventions. This study investigates the effects of curcumin on postmitotic cellular lifespan (PoMiCL) during chronological aging in yeast, a widely used model for human postmitotic cellular aging. Our findings reveal that curcumin significantly prolongs the PoMiCL of wildtype yeast cells, with the most pronounced effects observed at lower concentrations, indicating a hormetic response. Importantly, curcumin also extends the lifespan of postmitotic cells with mitochondrial deficiencies, although the hormetic effect is absent in these defective cells. Mechanistically, curcumin inhibits TORC1 activity, enhances ATP levels, and induces oxidative stress. These results suggest that curcumin has the potential to modulate aging and offer therapeutic insights into age-related diseases, highlighting the importance of context in its effects.

Rejuvenation Strategy for Inducing and Enhancing Autoimmune Response to Eliminate Senescent Cells.

The process of aging, which involves progressive changes in the body over time, is closely associated with the development of age-related diseases. Cellular senescence is a pivotal hallmark and mechanism of the aging process. The accumulation of senescent cells can significantly contribute to the onset of age-related diseases, thereby compromising overall health. Conversely, the elimination of senescent cells enhances the body's regenerative and reparative capacity, thereby retarding the aging process. Here, we present a brief overview of 12 Hallmarks of aging and subsequently emphasize the potential of immune checkpoint blockade, innate immune cell therapy (including T cells, iNKT cells, macrophages, and NK cells), as well as CAR-T cell therapy for inducing and augmenting immune responses aimed at eliminating senescent cells. In addition to CAR-T cells, we also explore the possibility of engineered immune cells such as CAR-NK and CAR-M cells to eliminate senescent cells. In summary, immunotherapy, as an emerging strategy for the treatment of aging, offers new prospects for age-related research.

Aberrant telomeric structures and serum markers of telomere dysfunction in healthy aging: a preliminary study.

Telomeres undergo a progressive shortening process as individuals age, and it has been proposed that severely shortened and dysfunctional telomeres play a role in the aging process and the onset of age-related diseases in human beings. An emerging body of evidence indicates that the shortening of telomeres in cultured human cells is also influenced by other replication defects occurring within telomeric repeats. These abnormalities can be detected on metaphase chromosomes. Recent studies have also identified a set of serological markers for telomere dysfunction and DNA damage (elongation factor 1α [EF-1α], stathmin, and N-acetyl-glucosaminidase). With this study, the correlation between telomere abnormalities (by FISH) and these biomarkers as measured in blood serum (by ELISA) from a cohort of 22 healthy subjects at different ages (range 26-101years) was analyzed. A strong positive correlation between aging and the presence of aberrant telomere structures, sister telomere loss(STL), and sister telomere chromatid fusions (STCF) was detected. When serum markers of telomere dysfunction were correlated with telomere abnormalities, we found that stathmin correlated with total aberrant telomeres structures (r = 0.431, p = 0.0453) and STCF (r = 0.533, p = 0.0107). These findings suggest that serum stathmin can be considered an easy-to-get marker of telomere dysfunction and may serve as valuable indicators of aging.

The Depression Anxiety Stress Scale 8: investigating its cutoff scores in relevance to loneliness and burnout among dementia family caregivers

The global trend of advanced aging comes at the cost of amplified onset of age-related diseases. Dementia is a common multifactorial age-related neurodegenerative disorder, which manifests with progressive declines in cognitive functioning and ability to perform activities of daily living. As polices discourage institutionalized care, family members act as primary caregivers and endure increased vulnerability to physical and mental health problems secondary to care-related changes in life routine and relationships. Targeting clinically significant distress at earlier stages through valid brief measures may promote caregivers’ wellbeing and dementia care continuity/quality. This study aimed to determine the optimal cutoff score of the Depression Anxiety Stress Scale 8-items (DASS-8) in a convenience sample of 571 European caregivers (Mean age = 53 ± 12 years, Italian = 74.4%, Swiss = 25.6%) through three methods. K-means clustering classified the sample into high- and low-distress clusters based on DASS-8 score of 19. Receiver operator curve (ROC) analysis using 48 and 7 cutoffs of the Zarit Burden Interview (ZBI) and the Three-Item University of California, Los Angeles, Loneliness Scale-version 3 (UCLALS3), revealed two DASS-8 cutoffs (12.5 and 14.5, area under the curve (AUC) = 0.85 and 0.92, p values < .001, 95% CI 0.82–0.88 and 0.89 to 0.94, sensitivity = 0.81 and 0.78, specificity = 0.76 and 0.89, Youden index = 0.57 and 0.67, respectively). Decision modeling produced two DASS-8 cutoffs (9.5 and 14.5) for predicting low and high caregiving burden and loneliness, respectively. According to the median of all DASS-8 cutoffs (14.5) the prevalence of mental distress was 50.8%. Distress correlated with key mental problems such as burnout and loneliness—in path analysis, DASS-8 scores were predicted by the ZBI, UCLALS3, care dependency, and receiving help with care, especially among older, female, and spouse caregivers. Further diagnostic workup should follow to confirm psycho-pathogenicity among caregivers with DASS-8 scores above 14.5. Investigations of the DASS-8 in other countries/populations may confirm the validity of this cutoff score.

Early life interventions metformin and trodusquemine metabolically reprogram the developing mouse liver through transcriptomic alterations.

Recent studies have demonstrated the remarkable potential of early life intervention strategies at influencing the course of postnatal development, thereby offering exciting possibilities for enhancing longevity and improving overall health. Metformin (MF), an FDA-approved medication for type II diabetes mellitus, has recently gained attention for its promising anti-aging properties, acting as a calorie restriction mimetic, and delaying precocious puberty. Additionally, trodusquemine (MSI-1436), an investigational drug, has been shown to combat obesity and metabolic disorders by inhibiting the enzyme protein tyrosine phosphatase 1b (Ptp1b), consequently reducing hepatic lipogenesis and counteracting insulin and leptin resistance. In this study, we aimed to further explore the effects of these compounds on young, developing mice to uncover biomolecular signatures that are central to liver metabolic processes. We found that MSI-1436 more potently alters mRNA and miRNA expression in the liver compared with MF, with bioinformatic analysis suggesting that cohorts of differentially expressed miRNAs inhibit the action of phosphoinositide 3-kinase (Pi3k), protein kinase B (Akt), and mammalian target of rapamycin (Mtor) to regulate the downstream processes of de novo lipogenesis, fatty acid oxidation, very-low-density lipoprotein transport, and cholesterol biosynthesis and efflux. In summary, our study demonstrates that administering these compounds during the postnatal window metabolically reprograms the liver through induction of potent epigenetic changes in the transcriptome, potentially forestalling the onset of age-related diseases and enhancing longevity. Future studies are necessary to determine the impacts on lifespan and overall quality of life.

Emerging insights into cuproptosis and copper metabolism: implications for age-related diseases and potential therapeutic strategies.

The expanding geriatric population, whose predisposition toward disabling morbidities and age-related diseases (ARD) is well-documented, has become a paramount social issue, exerting an onerous burden on both the healthcare industry and wider society. ARD manifest as the progressive deterioration of bodily tissues and organs, eventually resulting in the failure of these vital components. At present, no efficacious measures exist to hinder the onset of ARD. Copper, an essential trace element, is involved in a wide range of physiological processes across different cell types. In recent research, a novel variant of copper-dependent cell death, termed cuproptosis, has been identified. This mode of cellular demise stands apart from previously recognized types of cell death. Cuproptosis occurs when copper binds with acyl-CoA synthetase in the tricarboxylic acid (TCA) cycle, resulting in protein aggregation and protein toxicity stress, ultimately leading to cell death. In this paper, we provide a concise overview of the current understanding concerning the metabolism of copper, copper-related diseases, the hallmarks of copper toxicity, and the mechanisms that regulate copper toxicity. Additionally, we discuss the implications of cuproptosis mutations in the development of ARD, as well as the potential for targeting cuproptosis as a treatment for ARD.

Polyphenolic Compounds: Orchestrating Intestinal Microbiota Harmony during Aging.

In the aging process, physiological decline occurs, posing a substantial threat to the physical and mental well-being of the elderly and contributing to the onset of age-related diseases. While traditional perspectives considered the maintenance of life as influenced by a myriad of factors, including environmental, genetic, epigenetic, and lifestyle elements such as exercise and diet, the pivotal role of symbiotic microorganisms had been understated. Presently, it is acknowledged that the intestinal microbiota plays a profound role in overall health by signaling to both the central and peripheral nervous systems, as well as other distant organs. Disruption in this bidirectional communication between bacteria and the host results in dysbiosis, fostering the development of various diseases, including neurological disorders, cardiovascular diseases, and cancer. This review aims to delve into the intricate biological mechanisms underpinning dysbiosis associated with aging and the clinical ramifications of such dysregulation. Furthermore, we aspire to explore bioactive compounds endowed with functional properties capable of modulating and restoring balance in this aging-related dysbiotic process through epigenetics alterations.

Accelerated Aging Induced by an Unhealthy High-Fat Diet: Initial Evidence for the Role of Nrf2 Deficiency and Impaired Stress Resilience in Cellular Senescence.

High-fat diets (HFDs) have pervaded modern dietary habits, characterized by their excessive saturated fat content and low nutritional value. Epidemiological studies have compellingly linked HFD consumption to obesity and the development of type 2 diabetes mellitus. Moreover, the synergistic interplay of HFD, obesity, and diabetes expedites the aging process and prematurely fosters age-related diseases. However, the underlying mechanisms driving these associations remain enigmatic. One of the most conspicuous hallmarks of aging is the accumulation of highly inflammatory senescent cells, with mounting evidence implicating increased cellular senescence in the pathogenesis of age-related diseases. Our hypothesis posits that HFD consumption amplifies senescence burden across multiple organs. To scrutinize this hypothesis, we subjected mice to a 6-month HFD regimen, assessing senescence biomarker expression in the liver, white adipose tissue, and the brain. Aging is intrinsically linked to impaired cellular stress resilience, driven by dysfunction in Nrf2-mediated cytoprotective pathways that safeguard cells against oxidative stress-induced senescence. To ascertain whether Nrf2-mediated pathways shield against senescence induction in response to HFD consumption, we explored senescence burden in a novel model of aging: Nrf2-deficient (Nrf2+/-) mice, emulating the aging phenotype. Our initial findings unveiled significant Nrf2 dysfunction in Nrf2+/- mice, mirroring aging-related alterations. HFD led to substantial obesity, hyperglycemia, and impaired insulin sensitivity in both Nrf2+/- and Nrf2+/+ mice. In control mice, HFD primarily heightened senescence burden in white adipose tissue, evidenced by increased Cdkn2a senescence biomarker expression. In Nrf2+/- mice, HFD elicited a significant surge in senescence burden across the liver, white adipose tissue, and the brain. We postulate that HFD-induced augmentation of senescence burden may be a pivotal contributor to accelerated organismal aging and the premature onset of age-related diseases.

Perspective: Promoting Healthy Aging through Nutrition: A Research Centers Collaborative Network Workshop Report

Within 20 y, the number of adults in the United States over the age of 65 y is expected to more than double and the number over age 85 y is expected to more than triple. The risk for most chronic diseases and disabilities increases with age, so this demographic shift carries significant implications for the individual, health care providers, and population health. Strategies that delay or prevent the onset of age-related diseases are becoming increasingly important. Although considerable progress has been made in understanding the contribution of nutrition to healthy aging, it has become increasingly apparent that much remains to be learned, especially because the aging process is highly variable. Most federal nutrition programs and nutrition research studies define all adults over age 65 y as “older” and do not account for physiological and metabolic changes that occur throughout older adulthood that influence nutritional needs. Moreover, the older adult population is becoming more racially and ethnically diverse, so cultural preferences and other social determinants of health need to be considered. The Research Centers Collaborative Network sponsored a 1.5-d multidisciplinary workshop that included sessions on dietary patterns in health and disease, timing and targeting interventions, and health disparities and the social context of diet and food choice. The agenda and presentations can be found at https://www.rccn-aging.org/nutrition-2023-rccn-workshop. Here we summarize the workshop’s themes and discussions and highlight research gaps that if filled will considerably advance our understanding of the role of nutrition in healthy aging.

Direct neuronal reprogramming of NDUFS4 patient cells identifies the unfolded protein response as a novel general reprogramming hurdle

Mitochondria account for essential cellular pathways, from ATP production to nucleotide metabolism, and their deficits lead to neurological disorders and contribute to the onset of age-related diseases. Direct neuronal reprogramming aims at replacing neurons lost in such conditions, but very little is known about the impact of mitochondrial dysfunction on the direct reprogramming of human cells. Here, we explore the effects of mitochondrial dysfunction on the neuronal reprogramming of induced pluripotent stem cell (iPSC)-derived astrocytes carrying mutations in the NDUFS4 gene, important for Complex I and associated with Leigh syndrome. This led to the identification of the unfolded protein response as a major hurdle in the direct neuronal conversion of not only astrocytes and fibroblasts from patients but also control human astrocytes and fibroblasts. Its transient inhibition potently improves reprogramming by influencing the mitochondria-endoplasmic-reticulum-stress-mediated pathways. Taken together, disease modeling using patient cells unraveled novel general hurdles and ways to overcome these in human astrocyte-to-neuron reprogramming.

DEVELOPING A PROTOCOL TO ASSESS EXPOSURE TO ENVIRONMENTAL POLLUTANTS AMONG OLDER ADULT WOMEN IN SOUTHEAST MICHIGAN

Abstract Environmental pollutants, including PFAS, phthalates, and parabens, contribute to the development of age-related diseases like cancer, cardiometabolic disease, and neurodegenerative diseases. Unfortunately, these chemicals are common in everyday exposures, including drinking water, personal care products (PCPs), non-stick cookware, and food packaging. Exposures to these pollutants may be high in communities that have encountered structural disadvantages; neighborhood disinvestment and decaying infrastructure can make exposures to these pollutants more likely, thus increasing the burden of age-related disease in these communities. Interventions that reduce exposures to these chemicals may prevent or delay the onset of age-related disease, especially in groups experiencing poorer health outcomes because of structural racism and discrimination. To explore the feasibility of a behavior change intervention for older adults that reduces exposure to harmful chemicals in PCPs, a protocol was developed to: 1) Assess attitudes, knowledge, and behaviors related to environmental pollutants via questionnaire; 2) Characterize individual-level ‘exposomes’, the unique mixture of chemicals a person encounters in their everyday lives, by wearing a silicone wristband; 3) Measure environmental exposures in serum. Data collection will begin in September 2023 among older adult women who have participated in the Study of Women’s Health Across the Nation (SWAN) at the Michigan site. Older adults have accrued environmental exposures across their lifetimes, likely in a way that reflects patterns of structural disadvantage. While structural solutions are necessary to address issues of health equity, behavior change efforts can work in tandem to reduce harmful environmental exposures to improve the health of older adults.

Resilience to aging drives personalized intervention strategies for Alzheimer's disease.

There has been little progress in reducing the incidence and mortality of Alzheimer's disease (AD). Prevention of onset, more accurate diagnostic tools, and prediction of health outcomes have all been identified as critical issues, but more and better basic research approaches are needed. The single greatest risk factor associated with AD is aging. It follows that if aging can be delayed, there should be an equivalent delay or even prevention of the onset of AD neuropathology. Therefore, targeting multiple pathways of aging would be a powerful way to enhance resilience to aging and slow or prevent the onset of AD neuropathology and dementia in a personalized manner. More effective and predictive animal models, such as the aging pet cat that spontaneously develops neuropathology similar to human AD patients, are necessary to help validate noninvasive and inexpensive biomarkers for identifying individuals at risk. Resilience to aging and its ability to delay or prevent the onset of age-related diseases should be the focus for preventing brain aging and enhancing resistance to AD.

A promising therapeutic peptide and preventive/diagnostic biomarker for age-related diseases: The Elabela/Apela/Toddler peptide.

Elabela (ELA), Apela or Toddler peptide is a hormone peptide belonging to the adipokine group and a component of apelinergic system, discovered in 2013-2014. Given its high homology with apelin, the first ligand of APJ receptor, ELA likely mediates similar effects. Increasing evidence shows that ELA has a critical function not only in embryonic development, but also in adulthood, contributing to physiological and pathological conditions, such as the onset of age-related diseases (ARD). However, still little is known about the mechanisms and molecular pathways of ELA, as well as its precise functions in ARD pathophysiology. Here, we report the mechanisms by which ELA/APJ signaling acts in a very complex network of pathways for the maintenance of physiological functions of human tissue and organs, as well as in the onset of some ARD, where it appears to play a central role. Therefore, we describe the possibility to use the ELA/APJ pathway, as novel biomarker (predictive and diagnostic) and target for personalized treatments of ARD. Its potentiality as an optimal peptide candidate for therapeutic ARD treatments is largely described, also detailing potential current limitations.

Exercise mitigates age-related metabolic diseases by improving mitochondrial dysfunction.

The benefits of regular physical activity are related to delaying and reversing the onset of ageing and age-related disorders, including cardiomyopathy, neurodegenerative diseases, cancer, obesity, diabetes, and fatty liver diseases. However, the molecular mechanisms of the benefits of exercise or physical activity on ageing and age-related disorders remain poorly understood. Mitochondrial dysfunction is implicated in the pathogenesis of ageing and age-related metabolic diseases. Mitochondrial health is an important mediator of cellular function. Therefore, exercise alleviates metabolic diseases in individuals with advancing ageing and age-related diseases by the remarkable promotion of mitochondrial biogenesis and function. Exerkines are identified as signaling moieties released in response to exercise. Exerkines released by exercise have potential roles in improving mitochondrial dysfunction in response to age-related disorders. This review comprehensive summarizes the benefits of exercise in metabolic diseases, linking mitochondrial dysfunction to the onset of age-related diseases. Using relevant examples utilizing this approach, the possibility of designing therapeutic interventions based on these molecular mechanisms is addressed.

Early origins of health and disease risk: The case for investigating adverse exposures and biological aging in utero, across childhood, and into adolescence.

In this article, we suggest that aging and development are two sides of the same coin, and that developing a comprehensive understanding of health and disease risk requires examining age-related processes occurring throughout the earliest years of life. Compared to other periods in life, during this early period of acute vulnerability, when children's biological and regulatory systems are developing, biological aging occurs most rapidly. We review theory and empirical research suggesting that processes of development and aging are intricately linked, and that early adversity may program biological parameters for accelerated aging and disease risk early in life, even though clinical signs of age-related disease onset may not be evident until many years later. Following from this, we make the case for widespread incorporation of biological aging constructs into child development research.

Signs of aging in midlife: physical function and sex differences in microbiota.

Microbiota composition has been linked to physical activity, health measures, and biological age, but a shared profile has yet to be shown. The aim of this study was to examine the associations between microbiota composition and measures of function, such as a composite measure of physical capacity, and biological age in midlife, prior to onset of age-related diseases. Seventy healthy midlife individuals (age 44.58 ± 0.18) were examined cross-sectionally, and their gut-microbiota profile was characterized from stool samples using 16SrRNA gene sequencing. Biological age was measured using the Klemera-Doubal method and a composition of blood and physiological biomarkers. Physical capacity was calculated based on sex-standardized functional tests. We demonstrate that the women had significantly richer microbiota, p = 0.025; however, microbiota diversity was not linked with chronological age, biological age, or physical capacity for either women or men. Men had slightly greater β-diversity; however, β-diversity was positively associated with biological age and with physical capacity for women only (p = 0.01 and p = 0.04; respectively). For women, an increase in abundance of Roseburia faecis and Collinsella aerofaciens, as well as genus Ruminococcus and Dorea, was significantly associated with higher biological age and lower physical capacity; an increase in abundance of Akkermansia muciniphila and genera Bacteroides and Alistipes was associated with younger biological age and increased physical capacity. Differentially abundant taxa were also associated with non-communicable diseases. These findings suggest that microbiota composition is a potential mechanism linking physical capacity and health status; personalized probiotics may serve as a new means to support health-promoting interventions in midlife. Investigating additional factors underlying this link may facilitate the development of a more accurate method to estimate the rate of aging.

Retinal microvascular complexity as a putative biomarker of biological age: a pilot study.

Physiological changes associated with aging increase the risk for the development of age-related diseases. This increase is non-specific to the type of age-related disease, although each disease develops through a unique pathophysiologic mechanism. People who age at a faster rate develop age-related diseases earlier in their life. They have an older "biological age" compared to their "chronological age". Early detection of individuals with accelerated aging would allow timely intervention to postpone the onset of age-related diseases. This would increase their life expectancy and their length of good quality life. The goal of this study was to investigate whether retinal microvascular complexity could be used as a biomarker of biological age. Retinal images of 68 participants ages ranging from 19 to 82years were collected in an observational cross-sectional study. Twenty of the old participants had age-related diseases such as hypertension, type 2 diabetes, and/or Alzheimer's dementia. The rest of the participants were healthy. Retinal images were captured by a hand-held, non-mydriatic fundus camera and quantification of the microvascular complexity was performed by using Sholl's, box-counting fractal, and lacunarity analysis. In the healthy subjects, increasing chronological age was associated with lower retinal microvascular complexity measured by Sholl's analysis. Decreased box-counting fractal dimension was present in old patients, and this decrease was 2.1 times faster in participants who had age-related diseases (p = 0.047). Retinal microvascular complexity could be a promising new biomarker of biological age. The data from this study is the first of this kind collected in Montenegro. It is freely available for use.

Intimate Partner Violence and Inflammaging: Conflict Tactics Predict Inflammation Among Middle-Aged and Older Adults.

In long-term relationships, conflict is inevitable, but physical and psychological aggression is not. Intimate partner violence is a known risk factor for age-related disease onset, and inflammation likely links the two. This study explores relationships between frequency of constructive (i.e., negotiation) and destructive (i.e., aggression) conflict tactics with inflammation in both younger and older adulthood. Based on the theory of inflammaging, the study investigates whether these associations were stronger in mid-to-late adulthood. At one visit, 214 participants in long-term romantic relationships had their blood drawn to assess six inflammatory markers (interleukin-6 [IL-6], tumor necrosis factor α [TNF-α], C-reactive protein, serum amyloid A (SAA), soluble intercellular adhesion molecule (sICAM), soluble vascular cell adhesion molecule) and reported frequency of destructive and constructive conflict tactics with their partner in the past year on the Revised Conflict Tactics Scale short form. Age interacted with number of destructive conflicts per year to predict serum IL-6 ( F (1,200) = 5.3, p = .022), TNF-α ( F (1,180) = 4.2, p = .043), sICAM ( F (1,193) = 7.0, p = .008), and marginally SAA ( F (1,199) = 3.7, p = .055), such that middle-aged and older adults who reported more destructive tactics had higher inflammation. Also, the relationship between constructive conflict frequency and TNF-α also depended on age ( F (1,177) = 4.9, p = .029), in that older adults who reported a greater number of constructive tactics had lower TNF-α. Couples' conflict tactics may influence levels of inflammation and therefore aging rate in mid-to-late life. Middle-aged and older adults may disproportionately benefit from a healthy partnership and suffer from an unhealthy partnership.