Therapeutics For Age Related Diseases And Immune Dysfunction

Bonisiwe Shabane

-Dec 28, 2025, 4:51 AM

therapeutics for age related diseases and immune dysfunction

Nature Reviews Drug Discovery volume 24, pages 300–315 (2025)Cite this article Immunity declines with age. This results in a higher risk of age-related diseases, diminished ability to respond to new infections and reduced response to vaccines. The causes of this immune dysfunction are cellular senescence, which occurs in both lymphoid and non-lymphoid tissue, and chronic, low-grade inflammation known as ‘inflammageing’. In this Review article, we highlight how the processes of inflammation and senescence drive each other, leading to loss of immune function. To break this cycle, therapies are needed that target the interactions between the altered tissue environment and the immune system instead of targeting each component alone.

We discuss the relative merits and drawbacks of therapies that are directed at eliminating senescent cells (senolytics) and those that inhibit inflammation (senomorphics) in the context of tissue niches. Furthermore, we discuss therapeutic strategies designed to directly boost immune cell function and improve immune surveillance in tissues. This is a preview of subscription content, access via your institution Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value online-access subscription Our research integrity and auditing teams lead the rigorous process that protects the quality of the scientific record

These authors contributed equally to this work. Received 2024 Sep 28; Revised 2024 Oct 31; Accepted 2024 Nov 6; Collection date 2024 Nov. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Aging is the result of a complex interplay of physical, environmental, and social factors, leading to an increased prevalence of chronic age-related diseases that burden health and social care systems. As the global population ages, it is crucial to understand the aged immune system, which undergoes declines in both innate and adaptive immunity.

This immune decline exacerbates the aging process, creating a feedback loop that accelerates the onset of diseases, including infectious diseases, autoimmune disorders, and cancer. Intervention strategies, including dietary adjustments, pharmacological treatments, and immunomodulatory therapies, represent promising approaches to counteract immunosenescence. These interventions aim to enhance immune function by improving the activity and interactions of aging-affected immune cells, or by modulating inflammatory responses through the suppression of excessive cytokine secretion and inflammatory pathway activation. Such strategies have the potential to restore immune homeostasis and mitigate age-related inflammation, thus reducing the risk of chronic diseases linked to aging. In summary, this review provides insights into the effects and underlying mechanisms of immunosenescence, as well as its potential interventions, with particular emphasis on the relationship between aging, immunity, and nutritional factors. Keywords: aging, immune system, immunosenescence, immunotherapy, diet intervention

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Aging is characterized by a gradual decline in the functionality of all the organs and tissues, leading to various diseases. As the global population ages, the urgency to develop effective anti-aging strategies becomes increasingly critical due to the growing severity of associated health problems. Immunotherapy offers novel and promising approaches to combat aging by utilizing approaches including vaccines, antibodies, and cytokines to target specific aging-related molecules and pathways. In this review, we summarize the recent advancements of immunotherapies to eliminate senescence cells and senescence-associated secretory phenotypes (SASPs). Next, we describe immunotherapies against age-related diseases containing neurodegenerative diseases, vascular pathologies, type 2 diabetes (T2D), arthritis, osteoporosis, chronic obstructive pulmonary disease (COPD), fibrosis, skin aging, and cancer, detailing the targets, corresponding manipulations, and... Related problems including immunosenescence, serious adverse effects, the duality of function of senescent cells and SASPs, and inherent problems of immunotherapy are also discussed, suggesting directions for improvement.

In addition to recent development and challenges in the field, we describe a blueprint of personalized aging immunotherapy by multi-omics, Big Data, artificial intelligence (AI), and nanobots in the future, aiming to inspire the... Competing interests: The authors declare that they have no competing interests. Mechanisms of cellular senescence. Physical… Mechanisms of cellular senescence. Physical and chemical damage, telomere shortening, and oncogene activation…

Innovative strategies against aging. (A)… Our research integrity and auditing teams lead the rigorous process that protects the quality of the scientific record Images for download on the MIT News office website are made available to non-commercial entities, press and the general public under a Creative Commons Attribution Non-Commercial No Derivatives license. You may not alter the images provided, other than to crop them to size. A credit line must be used when reproducing images; if one is not provided below, credit the images to "MIT."

As people age, their immune system function declines. T cell populations become smaller and can’t react to pathogens as quickly, making people more susceptible to a variety of infections. To try to overcome that decline, researchers at MIT and the Broad Institute have found a way to temporarily program cells in the liver to improve T-cell function. This reprogramming can compensate for the age-related decline of the thymus, where T cell maturation normally occurs. Using mRNA to deliver three key factors that usually promote T-cell survival, the researchers were able to rejuvenate the immune systems of mice. Aged mice that received the treatment showed much larger and more diverse T cell populations in response to vaccination, and they also responded better to cancer immunotherapy treatments.

If developed for use in patients, this type of treatment could help people lead healthier lives as they age, the researchers say. You have full access to this open access article Aging is accompanied by a gradual decline in physiological resilience and an increased risk of chronic diseases collectively known as age-related disorders, including neurodegeneration, cardiovascular disease and osteoarthritis. Exosomes nano-sized extracellular vesicles have emerged as critical mediators in the aging process and related pathologies. By moving bioactive cargo such as proteins, lipids and mRNAs exosomes facilitate intercellular communication and modulate processes central to aging, including inflammation, immune response, senescence, and tissue repair. Exosomes contribute to “inflamm-aging,” influence stem cell function, and reflect age-associated molecular alterations, positioning them as potential biomarkers for early diagnosis and disease monitoring.

Understanding dual role of exosomes as both contributors to aging and platforms for intervention offers new avenues for promoting healthy longevity and mitigating the burden of age-associated diseases. Also, their inherent stability, low immunogenicity, and capacity for targeted delivery make exosomes promising candidates for therapeutic applications in regenerative medicine and anti-aging interventions. This review synthesizes current knowledge on exosome biogenesis, composition, and functional roles in aging and age-related diseases. We discuss emerging evidence supporting their use as diagnostic and prognostic tools and their potential in cell-free therapies aimed at modulating age-related decline. Despite their promise, several challenges impede clinical applications. Addressing these limitations will be essential to fully harnessing the therapeutic potential of exosomes in aging.

Notwithstanding these obstacles, exosomes exhibit significant potential for personalized and combinatorial therapies. Understanding the dual role of exosomes as both contributors to aging and tools for its modulation may open new avenues for interventions to promote healthy longevity. Avoid common mistakes on your manuscript. Aging is a multifactorial biological process marked by the gradual decline of physiological functions and increased vulnerability to a wide range of chronic diseases, collectively referred to as age-related disorders. These include cardiovascular diseases, neurodegenerative disorders like Alzheimer’s and Parkinson’s, osteoarthritis, musculoskeletal degeneration, and cognitive decline. As global life expectancy rises, the prevalence of these conditions places increasing stress on healthcare systems and impairs the quality of life for older individuals.

Therefore, understanding the fundamental mechanisms of aging and discovering novel therapeutic approaches are critical for promoting healthy longevity and mitigating the societal burden of age-related [1]. In this context, exosomes have emerged as a promising focus in geriatric and regenerative medicine. Exosomes are small extracellular vesicles (30–150 nm in diameter) secreted by various cell types [2,3,4]. They originate from the endosomal system and are released through the fusion of multivesicular bodies with the plasma membrane. These vesicles carry a rich cargo of proteins, lipids, messenger RNAs, non-coding RNAs, and microRNAs (miRNAs), enabling them to serve as key mediators of intercellular communication [5,6,7]. By facilitating the transfer of molecular signals, exosomes influence various physiological and pathological processes, including inflammation, senescence, immune response, and tissue regeneration, all of which are integral to the aging process [8].

The importance of exosomes in aging is multifaceted. First, they modulate systemic inflammation, a key hallmark of aging often referred to as “inflamm-aging” [9]. Second, they are implicated in the regulation of stem cell function and regenerative capacity—crucial processes that decline with age. Furthermore, they can carry age-altered bioactive molecules and serve as biomarkers for diagnosing and monitoring age-related conditions [10]. Finally, exosomes may be harnessed as therapeutic agents or delivery vehicles for anti-aging treatments due to their biocompatibility and capacity for targeted transport of therapeutic molecules. The biological properties of exosomes stem from their unique biogenesis and diverse cargo.

Exosomes are formed through the inward budding of endosomal membranes, generating multivesicular bodies (MVBs) within cells. These MVBs fuse with the plasma membrane to release exosomes into the extracellular environment. This biogenesis is tightly regulated and determines the composition of the exosomal cargo, which includes proteins (e.g., tetraspanins, heat shock proteins), nucleic acids (DNA, mRNA, and various non-coding RNAs), lipids (e.g., ceramides), and signaling...

Therapeutics For Age Related Diseases And Immune Dysfunction

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