Review
Version 6
Preserved in Portico This version is not peer-reviewed
Lipofuscin as the Main Driving Force of Current Age-Related Disease: Justification and Strategies for Removal
Version 1
: Received: 11 August 2022 / Approved: 12 August 2022 / Online: 12 August 2022 (08:05:09 CEST)
Version 2 : Received: 20 September 2022 / Approved: 21 September 2022 / Online: 21 September 2022 (03:36:55 CEST)
Version 3 : Received: 26 September 2022 / Approved: 27 September 2022 / Online: 27 September 2022 (04:20:31 CEST)
Version 4 : Received: 27 October 2022 / Approved: 28 October 2022 / Online: 28 October 2022 (05:21:13 CEST)
Version 5 : Received: 2 November 2022 / Approved: 2 November 2022 / Online: 2 November 2022 (03:41:32 CET)
Version 6 : Received: 19 March 2023 / Approved: 20 March 2023 / Online: 20 March 2023 (03:43:19 CET)
Version 7 : Received: 6 September 2023 / Approved: 6 September 2023 / Online: 7 September 2023 (03:36:15 CEST)
Version 8 : Received: 4 April 2024 / Approved: 5 April 2024 / Online: 8 April 2024 (13:40:34 CEST)
Version 9 : Received: 9 May 2024 / Approved: 9 May 2024 / Online: 10 May 2024 (00:49:36 CEST)
Version 2 : Received: 20 September 2022 / Approved: 21 September 2022 / Online: 21 September 2022 (03:36:55 CEST)
Version 3 : Received: 26 September 2022 / Approved: 27 September 2022 / Online: 27 September 2022 (04:20:31 CEST)
Version 4 : Received: 27 October 2022 / Approved: 28 October 2022 / Online: 28 October 2022 (05:21:13 CEST)
Version 5 : Received: 2 November 2022 / Approved: 2 November 2022 / Online: 2 November 2022 (03:41:32 CET)
Version 6 : Received: 19 March 2023 / Approved: 20 March 2023 / Online: 20 March 2023 (03:43:19 CET)
Version 7 : Received: 6 September 2023 / Approved: 6 September 2023 / Online: 7 September 2023 (03:36:15 CEST)
Version 8 : Received: 4 April 2024 / Approved: 5 April 2024 / Online: 8 April 2024 (13:40:34 CEST)
Version 9 : Received: 9 May 2024 / Approved: 9 May 2024 / Online: 10 May 2024 (00:49:36 CEST)
A peer-reviewed article of this Preprint also exists.
Renteln, M. Toward Systemic Lipofuscin Removal. Rejuvenation Research 2024, doi:10.1089/rej.2024.0034. Renteln, M. Toward Systemic Lipofuscin Removal. Rejuvenation Research 2024, doi:10.1089/rej.2024.0034.
Abstract
Lipofuscin is indigestible garbage that accumulates in the autophagic vesicles and cytosol of post-mitotic cells with age. Drs. Brunk and Terman postulated that lipofuscin accumulation is the main or at least a major driving factor in aging. They even posited that the evolution of memory is the reason why we get lipofuscin at all, as stable synaptic connections must be maintained over time, meaning that the somas of neurons must also remain in the same locale. In other words, they cannot dilute out their garbage over time through cell division. Mechanistically, their position certainly makes sense given that rendering a large percentage of a post-mitotic cell’s lysosomes useless must almost certainly negatively affect that cell and the surrounding microenvironment. Here, I explore the possibility that the accumulation of lipofuscin to some extent underlies all other categories of age-related damage as defined by Dr. Aubrey de Grey. I do not think that lipofuscin removal will reverse/prevent all forms of aging, just the major component facing us currently. In this piece, I will review what is known about lipofuscin accumulation from evolutionary and mechanistic standpoints and discuss ways of removing it from non-dividing (or slowly-dividing) cells.
Keywords
Anti-aging therapy; lipofuscin; SENS; TFEB; telomerase; and intracellular microbes
Subject
Medicine and Pharmacology, Oncology and Oncogenics
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Commenter: Michael Renteln
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