Table 3.

Single cell landscape of aging in mouse, rat and cynomolgus monkey

	Sample &Time & Platform and cell number	Conclusions
Mouse
2018, Tabula Muris Consortium443	(1) Brain, Thymus, Bone marrow, Kidney, Liver, Spleen, Lung, Small intestine, Peripheral blood; (2) 19 male and 11 female mice at 1, 3, 18, 21, 24, 30 months; (3) 10x Genomics (356,213 cells)	Molecular changes associated with the key hallmarks of aging can be observed in various tissues and cell types. For instance, in leukocytes, which are white blood cells, specific molecular alterations reflect the aging process. Old leukocytes often exhibit increased expression of pro-inflammatory markers and decreased expression of anti-inflammatory markers, indicating a shift towards a pro-inflammatory state.
2020, Tony Wyss-Coray group444	(1) Brain, Bone marrow, Kidney, Liver, Spleen, Lung, Intestine, Skin, Brown adipose tissue, WBC etc. (17 organs); (2) 4 male (1–27 months old) and 2 female (1–21 months old) mice (interval of 3 months); (3) Bulk RNA and plasma proteomics at 10 ages	Asynchronous inter- and intra-organ progression model of aging suggests that the aging process is not uniform across organs and tissues and can occur at different rates. Furthermore, widespread activation of immune cells becomes particularly prominent during aging. This immune cell activation is initially noticeable in white adipose depots during middle age, involving various immune cell types, including T cells, B cells, and plasma cells that express immunoglobulin J chain.
Rat
2020, Guang-Hui Liu Group445	(1) White adipose tissue, Brown adipose tissue, kidney, skin, liver, aortic tissues were isolated from randomly selected Y-AL; (2) Young ad libitum: 3 male and 3 female rats (5 months old); Old ad libitum: 2 male and 4 female rats (27 months old); Old caloric restriction: 3 male and 3 female rats (27 months old) animals; (3) 10x Genomics (166,111 cells)	The inflammatory response tends to increase with age. However, it has been observed that caloric restriction can have a systemic repressive effect on this inflammatory response. Then, abnormal cell-cell communication patterns are commonly observed during aging, particularly an excessive interplay of pro-inflammatory ligands and receptors. Lastly, interventions targeting metabolism have the potential to impact the overall immune response. These metabolic interventions may have a global effect on modulating the immune system during the aging process.
Cynomolgus monkey
2020, Guang-Hui Liu Group446	(1) Ovaries; (2) four juvenile (4, 5, 5, and 5 years old) and four aged (18, 19, 19, and 20 years old) cynomolgus monkeys; (3) STRT-sequencing (2601 cells)	The disruption of antioxidant signaling in early-stage oocytes and granulosa cells is a clear indication of oxidative damage as a critical factor in the decline of ovarian function with age. This oxidative damage is a significant contributor to the deterioration of the ovaries as it affects the delicate balance between ROS production and the antioxidant defense system. The impairment of antioxidant signaling pathways in these specific cell types further accentuates the susceptibility of the ovary to oxidative stress, leading to a decline in reproductive capacity and fertility as women age.
2021, Guang-Hui Liu Group447	Lung (n = 15) and heart (n = 6) monkeys (young 4–6 years old) and 8 old 18–21 years old). 10× Genomics single nucleus RNA-seq (109,609 for lung, 42,053 for heart)	Increased systemic inflammation is a hallmark of cardiopulmonary aging. With age, the expression of the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) is elevated in the pulmonary alveolar epithelial barrier, cardiomyocytes, and vascular endothelial cells. In addition, in aged cardiopulmonary tissues, there is an accumulation of IL-7, which induces ACE2 expression. Besides, it has been found that vitamin C can block the IL-7-induced ACE2 expression.
2020, Jing Qu group448	Aortic and coronary arteries from 8 young (4–6 years old) and 8 old (18–21 years) monkeys modified STRT-seq (8122 cells)	A comprehensive understanding of primate aortic and coronary vasculature aging at the single-cell level reveals the key role of FOXO3A downregulation in driving vascular dysfunction. This research provides insights into the molecular mechanisms underlying age-related changes in the primate vascular system. The study highlights that the downregulation of FOXO3A, a transcription factor involved in cellular stress response and longevity, plays a significant role in the development of vascular dysfunction associated with aging. The findings shed light on the specific molecular alterations occurring in the vasculature and emphasize the importance of FOXO3A as a potential therapeutic target for age-related vascular diseases.
2021, Jing Qu Group449	Neural retina and RPE-choroid layers from 8 young (4–6 years old) and 8 old (18–21 years) monkeys STRT-seq (total 7461 cells)	Oxidative stress is a prominent hallmark of aging in the neural retinal layer, while an intensified inflammatory response characterizes RPE and choroidal cells. Among the retinal cells, RPE cells are particularly susceptible to aging, exhibiting greater vulnerability compared to other cell types in the retina.