Longevity & Aging

Longevity and aging gene directions

Vertical axis: direction in long-lived vs short-lived mammals. Horizontal axis: direction with age. Reinforcing — same way on both axes. Divergent — immune programs up in both. Counteracting — longevity opposes the aging trend.

A·

Reinforcing

Expression shifts the same way in long-lived organisms and in aging — e.g. the GH/IGF1–insulin axis and lipid metabolism fall in both.

6 genes

B·

Divergent

Innate-immune programs (IL6, NF-κB, complement, TLR4) rise in both long-lived organisms and with age — a distinct-regulation case; interventions push them back down.

4 genes

C·

Counteracting

Longevity programs oppose the aging drift — mitobio/NAD⁺/sirtuins/proteostasis/telomerase stay high for longevity yet fall with age; stress axes (mTOR, GDF15, CRP, SASP) stay low for longevity yet rise with age.

13 genes

Reinforcing Divergent Counteracting Click a node to highlight its row ↓

SP121 · QUANTITATIVE LAYER

Longevity × aging program co-variation across the human cell atlas

15-gene longevity and 12-gene aging scores on SP121, summarized by system and cell type.

Validated release

1,246,365cells

10systems

47tissues

107cell types

Interpretation boundary Cells—not donors—are the analytical units. SP121 supplies no donor identifier or chronological-age field here, so these are descriptive score correlations only: no donor-level statistics, age association, p/q values, causal claims, or independent-cell inference.

SYSTEM VIEW

Full-data Spearman correlation

−1 0 +1

Motor system 0.355 r 0.331 Digestive system 0.288 r 0.273 Sensory system 0.248 r 0.251 Reproductive system 0.171 r 0.167 Cardiovascular system 0.155 r 0.137 Immune system 0.124 r 0.090 Urinary system 0.124 r 0.097 Respiratory system 0.097 r 0.092 Endocrine system 0.096 r 0.052 Nervous system 0.094 r 0.086

Bars share a fixed −1 to +1 domain. Values use every cell in each system; select a row to open the matching SP121 system view.

GROUP EXPLORER

Score scatter

Open atlas ↗

Level Group

Loading sampled display points…

Cells (full group)—

Pearson r—

Spearman ρ—

Display points—

Points are a capped visualization sample from frontend-summary.json; n and correlation coefficients are full-group results from summary.csv.

COMPLETE RELEASE SUMMARY

Body, system, tissue and cell-type correlations

165 groups

Level	Group	Cells	Pearson r	Spearman ρ	Method	Atlas
Whole body	whole_body	1,246,365	0.1486	0.1753	full cell-level descriptive correlation	Open ↗
System	Cardiovascular system	53,554	0.1368	0.1550	full cell-level descriptive correlation	Open ↗
System	Digestive system	147,706	0.2729	0.2882	full cell-level descriptive correlation	Open ↗
System	Endocrine system	119,655	0.0523	0.0959	full cell-level descriptive correlation	Open ↗
System	Immune system	376,788	0.0896	0.1244	full cell-level descriptive correlation	Open ↗
System	Motor system	62,054	0.3307	0.3553	full cell-level descriptive correlation	Open ↗
System	Nervous system	255,483	0.0858	0.0937	full cell-level descriptive correlation	Open ↗
System	Reproductive system	90,020	0.1674	0.1708	full cell-level descriptive correlation	Open ↗
System	Respiratory system	70,218	0.0920	0.0972	full cell-level descriptive correlation	Open ↗
System	Sensory system	25,247	0.2507	0.2485	full cell-level descriptive correlation	Open ↗
System	Urinary system	45,640	0.0969	0.1240	full cell-level descriptive correlation	Open ↗
Tissue	Adipose	117,207	0.0401	0.0828	full cell-level descriptive correlation	—
Tissue	Bladder	33,367	0.1054	0.1264	full cell-level descriptive correlation	—
Tissue	Blood	81,960	0.0601	0.0598	full cell-level descriptive correlation	—
Tissue	Bone marrow	21,485	-0.0894	-0.0748	full cell-level descriptive correlation	—
Tissue	CBL	27,787	0.0544	0.0628	full cell-level descriptive correlation	—
Tissue	Cartilage	16,490	0.1146	0.1196	full cell-level descriptive correlation	—
Tissue	Ear	2,660	0.0187	0.0277	full cell-level descriptive correlation	—
Tissue	Esophagus	5,530	0.0120	0.0311	full cell-level descriptive correlation	—
Tissue	Eye	14,050	0.1704	0.1760	full cell-level descriptive correlation	—
Tissue	Frontal lobe	20,509	0.0622	0.0629	full cell-level descriptive correlation	—
Tissue	Heart	23,794	0.1613	0.1790	full cell-level descriptive correlation	—
Tissue	Hippocampus	26,663	0.0084	0.0143	full cell-level descriptive correlation	—
Tissue	Hypothalamus	1,538	0.0761	0.0752	full cell-level descriptive correlation	—
Tissue	Kidney	12,273	0.1726	0.1918	full cell-level descriptive correlation	—
Tissue	Large Intestine	20,234	0.2635	0.2369	full cell-level descriptive correlation	—
Tissue	Liver	11,904	0.2927	0.3052	full cell-level descriptive correlation	—
Tissue	Lung	48,793	0.0688	0.0712	full cell-level descriptive correlation	—
Tissue	Lymph node	130,364	0.1041	0.1180	full cell-level descriptive correlation	—
Tissue	Mammary gland	27,841	0.1669	0.1671	full cell-level descriptive correlation	—
Tissue	Marrow	2,938	0.0870	0.1130	full cell-level descriptive correlation	—
Tissue	Muscle	5,718	0.0298	0.0372	full cell-level descriptive correlation	—
Tissue	Occipital lobe	23,677	0.0618	0.0721	full cell-level descriptive correlation	—
Tissue	Ovary	23,122	0.0839	0.0935	full cell-level descriptive correlation	—
Tissue	Pancreas	8,920	0.2882	0.3230	full cell-level descriptive correlation	—
Tissue	Parietal lobe	17,809	0.0351	0.0413	full cell-level descriptive correlation	—
Tissue	Prostate	15,367	0.2736	0.2785	full cell-level descriptive correlation	—
Tissue	Rectum	5,976	0.0865	0.1395	full cell-level descriptive correlation	—
Tissue	Salivary gland	22,530	0.3577	0.3776	full cell-level descriptive correlation	—
Tissue	Sciatic nerve	33,473	0.1563	0.1736	full cell-level descriptive correlation	—
Tissue	Skeletal muscle	39,846	0.1156	0.1068	full cell-level descriptive correlation	—
Tissue	Skin	22,587	0.2695	0.2523	full cell-level descriptive correlation	—
Tissue	Small Intestine	19,036	0.0958	0.1075	full cell-level descriptive correlation	—
Tissue	Small intestine	2,597	0.0305	0.0225	full cell-level descriptive correlation	—
Tissue	Spinal cord	53,663	0.0928	0.0972	full cell-level descriptive correlation	—
Tissue	Spleen	68,077	-0.0365	-0.0112	full cell-level descriptive correlation	—
Tissue	Stomach	28,043	0.1588	0.2043	full cell-level descriptive correlation	—
Tissue	Striatum	8,896	0.0390	0.0447	full cell-level descriptive correlation	—
Tissue	Temporal lobe	17,476	0.0422	0.0463	full cell-level descriptive correlation	—
Tissue	Testis	5,864	0.0711	0.0550	full cell-level descriptive correlation	—
Tissue	Thalamus	9,942	0.0897	0.0928	full cell-level descriptive correlation	—
Tissue	Thymus	39,409	0.1876	0.1809	full cell-level descriptive correlation	—
Tissue	Thyroid gland	2,448	0.1757	0.2112	full cell-level descriptive correlation	—
Tissue	Tongue	22,936	0.3020	0.3240	full cell-level descriptive correlation	—
Tissue	Tonsil	32,555	0.0518	0.0942	full cell-level descriptive correlation	—
Tissue	Trachea	21,425	0.1011	0.1021	full cell-level descriptive correlation	—
Tissue	Uterus	17,826	0.1130	0.1198	full cell-level descriptive correlation	—
Tissue	Vasculature	29,760	0.0603	0.0704	full cell-level descriptive correlation	—
Cell type	Acinar cells	3,157	0.3283	0.3176	full cell-level descriptive correlation	Open ↗
Cell type	Adipocyte progenitor cells	2,201	-0.0173	-0.0093	full cell-level descriptive correlation	Open ↗
Cell type	Adipocytes	11,862	0.0863	0.0863	full cell-level descriptive correlation	Open ↗
Cell type	Alveolar type 1 cells	469	-0.0043	0.0154	full cell-level descriptive correlation	Open ↗
Cell type	Alveolar type 2 cells	6,101	-0.0095	0.0000	full cell-level descriptive correlation	Open ↗
Cell type	Ascending loop of Henle cells	761	0.1839	0.1817	full cell-level descriptive correlation	Open ↗
Cell type	Astrocytes	20,075	0.0493	0.0522	full cell-level descriptive correlation	Open ↗
Cell type	B cells	122,701	0.1429	0.1644	full cell-level descriptive correlation	Open ↗
Cell type	Basal cells	19,841	0.2321	0.2494	full cell-level descriptive correlation	Open ↗
Cell type	Basophils	61	0.4570	0.5586	full cell-level descriptive correlation	Open ↗
Cell type	Bipolar cells	79	0.0726	0.0816	full cell-level descriptive correlation	Open ↗
Cell type	Cardiomyocytes	4,328	0.2106	0.2293	full cell-level descriptive correlation	Open ↗
Cell type	Cholangiocytes	445	0.1343	0.1310	full cell-level descriptive correlation	Open ↗
Cell type	Choroid plexus	6	0.0547	-0.1429	full cell-level descriptive correlation	Open ↗
Cell type	Ciliated cells	825	0.0007	0.0110	full cell-level descriptive correlation	Open ↗
Cell type	Club cells	3,241	0.0598	0.0669	full cell-level descriptive correlation	Open ↗
Cell type	Common myeloid progenitors	376	0.0471	0.0659	full cell-level descriptive correlation	Open ↗
Cell type	Connecting tubule cells	149	0.0055	0.0557	full cell-level descriptive correlation	Open ↗
Cell type	Cycling B cells	6,763	0.0892	0.1217	full cell-level descriptive correlation	Open ↗
Cell type	Cycling T cells	208	0.0574	0.0683	full cell-level descriptive correlation	Open ↗
Cell type	Cycling epithelial cells	15,472	0.4215	0.4367	full cell-level descriptive correlation	Open ↗
Cell type	Cycling gastric epithelial cell	168	0.0463	0.0738	full cell-level descriptive correlation	Open ↗
Cell type	Dendritic cells	6,128	0.1285	0.1566	full cell-level descriptive correlation	Open ↗
Cell type	Effector chondrocytes	2,284	0.0754	0.0664	full cell-level descriptive correlation	Open ↗
Cell type	Endoneurial cells	4,655	0.1519	0.1628	full cell-level descriptive correlation	Open ↗
Cell type	Endothelial cells	78,547	0.1329	0.1505	full cell-level descriptive correlation	Open ↗
Cell type	Enteric glial cells	973	0.2381	0.2334	full cell-level descriptive correlation	Open ↗
Cell type	Enteric neurons	46	0.1991	0.1816	full cell-level descriptive correlation	Open ↗
Cell type	Enterocytes	9,694	0.0620	0.0765	full cell-level descriptive correlation	Open ↗
Cell type	Ependymal cells	1,364	0.0681	0.0770	full cell-level descriptive correlation	Open ↗
Cell type	Epineurial cells	2,829	0.1858	0.1856	full cell-level descriptive correlation	Open ↗
Cell type	Erythroid cells	12,887	0.4770	0.3396	full cell-level descriptive correlation	Open ↗
Cell type	Excitatory neurons	45,096	0.0859	0.0833	full cell-level descriptive correlation	Open ↗
Cell type	Fibroblasts	58,656	0.1648	0.1771	full cell-level descriptive correlation	Open ↗
Cell type	Fibrocartilage chondrocytes	300	0.1740	0.1248	full cell-level descriptive correlation	Open ↗
Cell type	Follicular cells	554	0.2016	0.2098	full cell-level descriptive correlation	Open ↗
Cell type	Glandular cells	724	-0.0573	-0.0764	full cell-level descriptive correlation	Open ↗
Cell type	Goblet cells	3,047	0.0492	0.0590	full cell-level descriptive correlation	Open ↗
Cell type	Granule cells	23,771	0.0288	0.0393	full cell-level descriptive correlation	Open ↗
Cell type	Granulocytes	100	0.2722	0.2233	full cell-level descriptive correlation	Open ↗
Cell type	Hematopoietic stem and progenitor cells	780	0.0557	0.0483	full cell-level descriptive correlation	Open ↗
Cell type	Hepatocytes	2,712	0.0049	0.0045	full cell-level descriptive correlation	Open ↗
Cell type	Homeostatic chondrocytes	4,518	0.1273	0.1234	full cell-level descriptive correlation	Open ↗
Cell type	Hypertrophic chondrocytes	1,363	0.0698	0.0829	full cell-level descriptive correlation	Open ↗
Cell type	Inflammatory chondrocytes	70	0.0390	0.0610	full cell-level descriptive correlation	Open ↗
Cell type	Inhibitory neurons	41,926	0.0458	0.0472	full cell-level descriptive correlation	Open ↗
Cell type	Intercalated cells	696	0.0684	0.0816	full cell-level descriptive correlation	Open ↗
Cell type	Keratinocytes	3,938	0.0505	0.0607	full cell-level descriptive correlation	Open ↗
Cell type	Kupffer cells	1,957	0.0932	0.1003	full cell-level descriptive correlation	Open ↗
Cell type	Luminal epithelial cells	22,063	0.2874	0.2995	full cell-level descriptive correlation	Open ↗
Cell type	Macrophages	84,876	0.0888	0.1039	full cell-level descriptive correlation	Open ↗
Cell type	Mast cells	3,561	0.0807	0.1116	full cell-level descriptive correlation	Open ↗
Cell type	Medullary thymus epithelial cells	190	0.0735	0.1167	full cell-level descriptive correlation	Open ↗
Cell type	Megakaryocyte erythrocyte progenitors	329	0.1255	0.1344	full cell-level descriptive correlation	Open ↗
Cell type	Melanocytes	1,451	0.0566	0.0766	full cell-level descriptive correlation	Open ↗
Cell type	Mesenchymal cells	21,836	0.1846	0.1626	full cell-level descriptive correlation	Open ↗
Cell type	Mesothelial cells	4,034	-0.0115	-0.0122	full cell-level descriptive correlation	Open ↗
Cell type	Microglia	13,681	0.0164	0.0200	full cell-level descriptive correlation	Open ↗
Cell type	Monocytes	77,497	-0.1250	-0.1449	full cell-level descriptive correlation	Open ↗
Cell type	Mucous cells	3,505	0.1804	0.1936	full cell-level descriptive correlation	Open ↗
Cell type	Muller cells	69	0.2220	0.2393	full cell-level descriptive correlation	Open ↗
Cell type	Natural killer T cells	21,060	0.0670	0.0849	full cell-level descriptive correlation	Open ↗
Cell type	Natural killer cells	13,873	0.0746	0.0855	full cell-level descriptive correlation	Open ↗
Cell type	Neutrophils	21,396	-0.1236	-0.1101	full cell-level descriptive correlation	Open ↗
Cell type	Oligodendrocyte progenitor cells	9,100	0.0297	0.0410	full cell-level descriptive correlation	Open ↗
Cell type	Oligodendrocytes	50,763	0.0378	0.0463	full cell-level descriptive correlation	Open ↗
Cell type	Other stromal cells	33,374	0.2160	0.2263	full cell-level descriptive correlation	Open ↗
Cell type	Pancreas ductal cells	1,640	0.1322	0.1506	full cell-level descriptive correlation	Open ↗
Cell type	Pancreas islet cells	90	0.2753	0.2892	full cell-level descriptive correlation	Open ↗
Cell type	Parietal cells	22	0.0455	0.1124	full cell-level descriptive correlation	Open ↗
Cell type	Pericytes	13,150	0.1847	0.2162	full cell-level descriptive correlation	Open ↗
Cell type	Perineurial cells	6,971	0.1480	0.1479	full cell-level descriptive correlation	Open ↗
Cell type	Peritubular myoid cells	93	0.0705	0.0594	full cell-level descriptive correlation	Open ↗
Cell type	Plasma B cells	20,394	0.1859	0.2206	full cell-level descriptive correlation	Open ↗
Cell type	Platelets	814	0.0222	0.0485	full cell-level descriptive correlation	Open ↗
Cell type	Podocytes	63	0.2060	0.1983	full cell-level descriptive correlation	Open ↗
Cell type	Pre-hypertrophic chondrocytes	1,476	0.1113	0.1139	full cell-level descriptive correlation	Open ↗
Cell type	Pre-inflammatory chondrocytes	26	-0.3702	-0.3242	full cell-level descriptive correlation	Open ↗
Cell type	Precursor fibrocartilage chondrocytes	2,584	0.1017	0.1033	full cell-level descriptive correlation	Open ↗
Cell type	Principal cells	1,484	0.0859	0.1045	full cell-level descriptive correlation	Open ↗
Cell type	Progenitor-like epithelial cells	49	0.0751	0.1098	full cell-level descriptive correlation	Open ↗
Cell type	Proliferative chondrocytes	963	0.0181	0.0126	full cell-level descriptive correlation	Open ↗
Cell type	Proximal tubule cells	5,808	0.1686	0.1666	full cell-level descriptive correlation	Open ↗
Cell type	Regulatory chondrocytes	1,992	0.1136	0.1015	full cell-level descriptive correlation	Open ↗
Cell type	Reparative chondrocytes	914	0.1248	0.1064	full cell-level descriptive correlation	Open ↗
Cell type	Retinal pigmentary epithelial cells	1,353	0.1321	0.1386	full cell-level descriptive correlation	Open ↗
Cell type	Rod cells	1,637	0.1564	0.1891	full cell-level descriptive correlation	Open ↗
Cell type	Satellite cells	7,872	0.1465	0.1714	full cell-level descriptive correlation	Open ↗
Cell type	Schwann cells	9,823	0.1926	0.2100	full cell-level descriptive correlation	Open ↗
Cell type	Serous cells	9,050	0.3486	0.3871	full cell-level descriptive correlation	Open ↗
Cell type	Smooth muscle cells	31,658	0.1386	0.1386	full cell-level descriptive correlation	Open ↗
Cell type	Spermatids	2,695	0.0785	0.0742	full cell-level descriptive correlation	Open ↗
Cell type	Spermatocytes	2,302	0.0643	0.0433	full cell-level descriptive correlation	Open ↗
Cell type	Spermatogonia	659	0.0650	0.0588	full cell-level descriptive correlation	Open ↗
Cell type	Squamous cells	539	0.0151	0.0150	full cell-level descriptive correlation	Open ↗
Cell type	Stellate cells	690	0.1224	0.1306	full cell-level descriptive correlation	Open ↗
Cell type	Supporting cells of vestibular epithelium	216	-0.0096	-0.0414	full cell-level descriptive correlation	Open ↗
Cell type	Surface epithelial cells	1,166	0.1311	0.1242	full cell-level descriptive correlation	Open ↗
Cell type	T cells	172,870	0.1135	0.1322	full cell-level descriptive correlation	Open ↗
Cell type	Taste cells	496	-0.0343	-0.0496	full cell-level descriptive correlation	Open ↗
Cell type	Tendon cells	334	0.1071	0.0594	full cell-level descriptive correlation	Open ↗
Cell type	Theca cells	13,661	0.0893	0.0981	full cell-level descriptive correlation	Open ↗
Cell type	Thymocytes	5,664	0.1366	0.1201	full cell-level descriptive correlation	Open ↗
Cell type	Type I myonuclei	126	0.2899	0.2500	full cell-level descriptive correlation	Open ↗
Cell type	Type II myonuclei	398	0.4611	0.5232	full cell-level descriptive correlation	Open ↗
Cell type	Urothelial cells	13,016	0.1032	0.0912	full cell-level descriptive correlation	Open ↗
Cell type	Vestibular dark cells	45	-0.1490	-0.2000	full cell-level descriptive correlation	Open ↗

ReleaseSP121-aging-correlation-full-r20260813T200000Z

Whole-body resultr 0.1486 · ρ 0.1753

▸ Gene × Direction Catalog (23 genes)

Curated longevity and aging gene relationship catalog
Symbol	Gene	Longevity	Aging	Pathway	Relationship	Evidence	Mechanism / note	PubMed
IGF1	Insulin-like growth factor 1	▼ Down	▼ Down	GH/IGF1 - insulin signaling	Reinforcing	Established	Key example: downregulated in BOTH long-lived species AND with age (paper's core "not all aging changes detrimental" point). Class-level IIS review (Cheng 2005).	PMID 15800976 ↗
IGF1R	IGF1 receptor	▼ Down	▼ Down	GH/IGF1 - insulin signaling	Reinforcing	Established	Insulin/IGF-1 axis; reduced signaling is a conserved longevity signature and declines with age. IGF1R mutations in Ashkenazi centenarians (Suh et al. 2008).	PMID 18316725 ↗
IRS2	Insulin receptor substrate 2	▼ Down	▼ Down	Insulin signaling	Reinforcing	Candidate	Insulin/IGF-1 signaling effector; downregulated in long-lived and with age. Reduced Irs2 signaling extends mouse lifespan (Taguchi et al. 2007).	PMID 17641201 ↗
APOC3	Apolipoprotein C-III	▼ Down	▼ Down	Lipid metabolism	Reinforcing	Established	Shared longevity signature; low APOC3 linked to longevity and lower lipid burden with age. APOC3 -641C and exceptional longevity (Atzmon et al. 2006).	PMID 16602826 ↗
CETP	Cholesteryl ester transfer protein	▼ Down	▼ Down	Lipid metabolism	Reinforcing	Candidate	Reduced CETP activity/lipid transport associated with longevity. CETP I405V enriched in exceptional longevity (Barzilai et al. 2003).	PMID 14559957 ↗
ACE	Angiotensin-converting enzyme	▼ Down	▼ Down	Renin-angiotensin system	Reinforcing	Candidate	Longevity-associated ACE variant (DD) with altered RAAS activity; angiotensin declines in function with age. ACE locus association in centenarians (Schachter et al. 1994).	PMID 8136829 ↗
IL6	Interleukin-6	▲ Up	▲ Up	Innate immunity / inflammaging	Divergent	Established	Up in long-lived species (adaptive DAMPs clearance) AND rises with age (inflammaging); interventions DOWN-regulate it - the paper's distinct-regulation case.	PMID 24833586 ↗
NFKB1	NF-kappa-B subunit 1	▲ Up	▲ Up	NF-kB / innate immunity	Divergent	Established	NF-kB drives both longevity-associated innate response and age-related chronic inflammation.	PMID 24833586 ↗
C3	Complement C3	▲ Up	▲ Up	Complement / innate immunity	Divergent	Candidate	Complement pathway up in long-lived mammals; complement activation rises with age.	PMID 24833586 ↗
TLR4	Toll-like receptor 4	▲ Up	▲ Up	Innate immunity	Divergent	Candidate	Innate immune sensing up in long-lived species and with age (chronic inflammation).	PMID 24833586 ↗
PPARGC1A	PGC-1alpha	▲ Up	▼ Down	Mitochondrial biogenesis	Counteracting	Candidate	Master mitobiogenesis regulator: high in long-lived (mito translation/program) but declines with age - longevity restores the aging decline.	PMID 20134150 ↗
NAMPT	Nicotinamide phosphoribosyltransferase	▲ Up	▼ Down	NAD+ biosynthesis	Counteracting	Candidate	Rate-limiting NAD+ enzyme: upregulated in longevity programs, declines with age (NAD+ loss).	PMID 24786309 ↗
SIRT1	Sirtuin 1	▲ Up	▼ Down	NAD+/sirtuin - proteostasis	Counteracting	Candidate	Activity/expression tracks longevity; declines with age - anti-aging axis.	PMID 32084459 ↗
SIRT3	Sirtuin 3	▲ Up	▼ Down	Mitochondrial sirtuin	Counteracting	Candidate	Mitochondrial deacetylase: supports longevity, declines with age.	PMID 32084459 ↗
KLOTHO	Klotho	▲ Up	▼ Down	Anti-aging hormone / phosphate & IGF1	Counteracting	Candidate	Soluble Klotho is a longevity hormone; declines with age - supplementing it opposes aging.	PMID 19230844 ↗
HSPA1A	Heat shock protein 70 (HSP70)	▲ Up	▼ Down	Proteostasis / proteolysis	Counteracting	Candidate	Chaperone up in longevity, declines with age; proteostasis is a shared longevity mechanism (paper).	PMID 31997665 ↗
PSMA5	Proteasome subunit alpha 5	▲ Up	▼ Down	Proteolysis / proteasome	Counteracting	Candidate	Proteolytic capacity enriched in long-lived signatures (paper); declines with age.	PMID 31997665 ↗
TERT	Telomerase reverse transcriptase	▲ Up	▼ Down	Telomere maintenance	Counteracting	Established	Telomerase activity supports longevity/telomere length; declines with age as telomeres shorten.	PMID 18391173 ↗
mTOR	Mammalian target of rapamycin	▼ Down	▲ Up	MTOR / nutrient sensing	Counteracting	Candidate	Rapamycin target; mTORC1 activity reduced for longevity but rises with age - intervention reverses aging.	PMID 37142830 ↗
GDF15	Growth differentiation factor 15	▼ Down	▲ Up	Inflammation / stress (hormokine)	Counteracting	Established	GDF15 rises with age/stress; longevity programs keep it low - inverse relationship.	PMID 37190783 ↗
CRP	C-reactive protein	▼ Down	▲ Up	Inflammation (clinical)	Counteracting	Established	Long-lived populations show low CRP; CRP rises with age and predicts mortality.	PMID 40444244 ↗
CD28	CD28 (T-cell costimulation)	▲ Up	▼ Down	Immunosenescence	Counteracting	Established	CD28+ T cells retained in long-lived; loss marks senescent T cells with age.	PMID 38471362 ↗
SASP	SASP (senescence secretome)	▼ Down	▲ Up	Cellular senescence	Counteracting	Established	Senescent-cell secretome reduced by longevity programs, accumulates with age driving dysfunction.	PMID 38654098 ↗

Directions are relative qualitative calls (up/down) from the curated longevity set. Pattern A = same direction both axes; B = both axes up (distinct-regulation immune case); C = longevity opposes the aging trend. Evidence: Established = replicated · Candidate = model organisms / emerging. PMIDs are representative refs — verify before citing.