Targeting the SASP to combat ageing: Mitochondria as possible intracellular allies?
Open accessAbstract
Anti‐senescence therapies, such as drugs that specifically kill senescent cells, to stave off ageing are currently under investigation. While these interventions show promise, their potential pitfalls are discussed herein. We have shown that the mitochondria are essential for development of senescence and many of the associated phenotypes, including the often detrimental senescence‐associated secretory phenotype (SASP). Here, we disentangle many ways in which the mitochondria may influence senescence and development of the SASP and focus on possible pathways that could be exploited for future generation of anti‐senescence therapies with a clear aim; to specifically eliminate the problematic features of senescent cells, while maintaining their beneficial characteristics.
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Mitochondria in senescent cells are more abundant but their ability to produce ATP is compromised.
“While mitochondria are more abundant, it appears their ability to produce ATP is compromised (Birch and Passos, 2017; Korolchuk et al., 2017).”
From Cellular Senescence: Defining a Path Forward (2019) · cites this paper as Birch and Passos, 2017
The “Mitochondrial metabolism in SASP regulation” section describes mitochondrial biogenesis in a senescence-related feedback loop and links increased AMP:ATP and ADP:ATP ratios to senescence (page not available in our copy). It does not establish that senescent cells generally have more mitochondria or that their mitochondria have a reduced ability to produce ATP. (LLM, conf=0.78)
Experimental — accuracy not yet measuredReduced NAD+/NADH ratios could alter the activity of PARP and sirtuins, both involved in activation of the SASP regulator NF-kB.
“NAD + /NADH ratios are reduced in senescent cells (Wiley et al., 2016), which could alter the activity of poly-ADP ribose polymerase (PARP) and sirtuins, both involved in activation of the SASP regulator NF-kB (Birch and Passos, 2017).”
From Cellular Senescence: Defining a Path Forward (2019) · cites this paper as Birch and Passos, 2017
The ‘Mitochondrial metabolism in SASP regulation’ section says that low NAD+/NADH can affect the SASP and that both PARPs and sirtuins require NAD+. It links sirtuins to NF-kB regulation, but describes them as inhibitors of NF-kB activity; it does not establish that PARPs activate NF-kB. Thus the proposed effect on PARPs and sirtuins is supported, but the claim that both are involved in NF-kB activation is not fully supported. (LLM, conf=0.85)
Experimental — accuracy not yet measuredAltered AMP:ATP and ADP:ATP ratios during senescence contribute to cell-cycle withdrawal by activating AMPK.
“Altered AMP:ATP and ADP:ATP ratios during senescence contribute to cell-cycle withdrawal by activating AMPK (AMP-activated protein kinase), a main sensor of energy deprivation (Birch and Passos, 2017).”
From Cellular Senescence: Defining a Path Forward (2019) · cites this paper as Birch and Passos, 2017
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- Authors
- Birch, J., & Passos, J. F.
- Affiliations
- Newcastle University (GB)
- Corresponding author
- Passos, João F.
- Venue
- BioEssays
- Publisher
- Wiley
- Published
- 2017-02-20
- Volume
- 39
- Issue
- 5
- ISSN
- 0265-9247 (ISSN-L)
- 1521-1878
- OpenAlex
- W2589270139
- Cited by
- 89
- References
- 28
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 10 · 2023: 8 · 2022: 11 · 2021: 18 · 2020: 10 · 2019: 11 · 2018: 7 · 2017: 2
- FWCI
- 1.01
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- BioEssays (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity) (cc-by)
- Funders
- Biotechnology and Biological Sciences Research Council
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- senescence-associated secretory phenotype, mitochondrial function, cellular senescence, anti-senescence therapy, senolytics, aging, senescence-associated secretome
- MeSH terms
- Alarmins, Aging, Animals, DNA Damage, Humans, Mitochondria, Models, Biological, Cellular Senescence, TOR Serine-Threonine Kinases
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