Immunosenescence and Ageing: An Entangled Web of Senescence and Declining Immunity

Aug 6, 2025Frontiers in bioscience (Landmark edition)

Aging and Immune System Decline: How Cell Aging and Weakening Immunity Are Linked

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Abstract

Cellular senescence, a durable cell-cycle arrest, plays a significant role in the ageing process.

Cellular senescence is associated with the release of molecules that attract immune cells for clearance.
Chronic senescence may occur due to immune deficiencies that develop with age.
Immunosenescence, or the ageing of immune cells, is linked to the worsening effects of senescence on health.
Animal studies suggest that thymic regeneration could restore immune function and reverse aspects of ageing.
Senolytic and senomorphic drugs show promise in targeting senescent cells but require careful application to maintain their vital functions.

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Ageing is a progressive functional decline in health conditions and a risk factor for many chronic diseases. To address the elevated burden of age-related pathologies, the ageing process has been extensively studied over the past decades, and yet the underlying mechanisms remain to be fully understood. One of the prominent features of ageing is cellular senescence, a special form of durable cell-cycle arrest. While senescent cells release the senescence-associated secretory phenotype (SASP) molecules that recruit immune cells to facilitate the clearance of senescent cells, senescence is also indispensable for many essential physiological functions. However, a 'chronic' nature of senescence arises due to immune deficiencies and persists during ageing. Immunosenescence, the ageing of immune cells, is the underlying key driving the pathological burdens of senescence, leading to systemic ageing as demonstrated by animal studies. Thymic regeneration has been shown by several studies to be a potential anti-ageing intervention, restoring immunity as well as reversing immunosenescence and ageing. The specific targeting of senescent cells by senolytic and/or senomorphic drugs is also promising but needs to be dealt with caution to protect the essential physiological roles of senescence. A deeper understanding of the biological origins of immunosenescence is crucial for unveiling the potential root cause of ageing.

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Immunosenescence and Ageing: An Entangled Web of Senescence and Declining Immunity

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